National Comprehensive Cancer Network (NCCN) Approved Recommendations
Rituximab (Rituxan) may be considered medically necessary for ANY of the following indications:
Acute Lymphoblastic Leukemia (ALL)
- Induction/consolidation therapy for Philadelphia chromosome-negative ALL in adolescent and young adult (AYA) and adult individuals less than 65 years of age as a component of:
- GRAALL-2005 regimen (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide) with rituximab for CD20-positive disease (individuals aged less than 60 years); or
- HyperCVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose methotrexate and cytarabine), with or without rituximab for CD20-positive disease; or
- Induction therapy for Philadelphia chromosome-negative ALL in adults aged greater than or equal to 65 years as a component of GMALL (idarubicin, dexamethasone, vincristine, cyclophosphamide, and cytarabine, with or without rituximab for CD20-positive disease) (moderate intensity); or
- Therapy for relapsed/refractory Philadelphia chromosome-negative ALL or for relapsed/refractory Philadelphia chromosome-positive ALL refractory to TKIs as a component of MOpAD regimen (methotrexate, vincristine, pegaspargase, dexamethasone) with rituximab for CD20-positive disease; or
- Therapy for relapsed/refractory Philadelphia chromosome-positive ALL as a component of MOpAD regimen (methotrexate, vincristine, pegaspargase, dexamethasone) with rituximab for CD20-positive disease and TKI; or
B-Cell Lymphoma - AIDS-Related
- Treatment in combination with growth factor support for AIDS-related Burkitt lymphoma as a component of:
- DA-EPOCH-R (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen; or
- Modified CODOX-M (cyclophosphamide, doxorubicin, and vincristine, with intrathecal methotrexate and cytarabine followed by high-dose systemic methotrexate) regimen alternating with IVAC (ifosfamide, cytarabine, etoposide, and intrathecal methotrexate) regimen with rituximab; or
- In combination with growth factor support for AIDS-related Burkitt lymphoma as a component of R-HyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine) regimen; or
- Second-line therapy for relapse of AIDS-related Burkitt lymphoma as a component of:
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab (if not previously given as first-line therapy); or
- RICE (rituximab, ifosfamide, carboplatin, and etoposide) regimen in combination with intrathecal methotrexate (if not previously given); or
- RIVAC (rituximab, ifosfamide, cytarabine, etoposide) regimen in combination with intrathecal methotrexate (if not previously given); or
- RGDP (rituximab, gemcitabine, dexamethasone, cisplatin) regimen; or
- High-dose cytarabine and rituximab regimen; or
- Treatment In combination with growth factor support for CD20+ AIDS-related diffuse large B-cell lymphoma (DLBCL) primary effusion lymphoma and HHV8-positive DLBCL, not otherwise specified (NOS) as a component of R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen; or
- In combination with growth factor support for CD20+ AIDS-related diffuse large B-cell lymphoma and HHV8-positive DLBCL, not otherwise specified (NOS) as a component of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen with rituximab; or
- Used for relapsed AIDS-related DLBCL, HHV8-positive DLBCL, not otherwise specified (NOS), and primary effusion lymphoma in combination with bortezomib-ICE (ifosfamide, carboplatin, and etoposide) regimen; or
- Second-line therapy or subsequent therapy for relapse of AIDS-related DLBCL, primary effusion lymphoma, and HHV8-positive DLBCL, not otherwise specified (NOS):
- For individuals with intention to proceed to transplant as a component of DHAP (dexamethasone, cisplatin, and cytarabine), DHAX (dexamethasone, cytarabine, and oxaliplatin), ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin), GDP (gemcitabine, dexamethasone, and cisplatin or gemcitabine, dexamethasone, and carboplatin), GemOX (gemcitabine and oxaliplatin), ICE (ifosfamide, carboplatin, and etoposide), or MINE (mesna, ifosfamide, mitoxantrone, and etoposide) regimen with rituximab; or
- In non-candidates for transplant as a single agent, in combination with polatuzumab vedotin-piiq with or without bendamustine (greater than or equal to two (2) prior therapies), with lenalidomide (for non-germinal center DLBCL) or bendamustine, with gemcitabine and vinorelbine, or as a component of CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine), dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), CEOP (cyclophosphamide, etoposide, vincristine, and prednisone), GDP, or GemOX regimen with rituximab; or
B-Cell Lymphomas - Burkitt Lymphoma
- Induction therapy for low-risk disease for individuals less than 60 years of age as a component of:
- CODOX-M (cyclophosphamide, doxorubicin, and vincristine, with intrathecal methotrexate and cytarabine followed by high-dose systemic methotrexate) regimen (original or modified) regimen with rituximab; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab and intrathecal methotrexate; or
- HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose methotrexate and cytarabine regimen with rituximab(regimen includes intrathecal therapy); or
- Induction therapy for high-risk disease in individuals less than 60 years of age as a component of:
- CODOX-M (cyclophosphamide, doxorubicin, and vincristine, with intrathecal methotrexate and cytarabine followed by high-dose systemic methotrexate) regimen (original or modified) alternating with IVAC (ifosfamide, cytarabine, etoposide, and intrathecal methotrexate) regimen with rituximab; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab and intrathecal methotrexate for individuals not able to tolerate aggressive therapy; or
- Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose methotrexate and cytarabine regimen with rituximab (regimen includes intrathecal therapy); or
- Induction therapy for low-risk and high-risk disease in individuals 60 years of age or older as a component of dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab and intrathecal methotrexate; or
- Used as a component of dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab and intrathecal methotrexate, RICE (rituximab, ifosfamide, carboplatin, and etoposide) regimen with intrathecal methotrexate if not previously given, RIVAC (rituximab, ifosfamide, cytarabine, and etoposide) regimen with intrathecal methotrexate if not previously given:
- As second-line therapy for relapse of Burkitt lymphoma greater than 6-18 months following appropriate first-line therapy; or
- For individuals with partial response to second-line therapy as additional therapy (if not previously given) for relapse or refractory disease; or
- Second-line therapy for individuals with disease relapse greater than 6-18 months after appropriate first-line therapy or for individuals with partial response to second-line therapy as additional therapy (if not previously given) for relapsed or refractory disease:
- As a component of RGDP (rituximab, gemcitabine, dexamethasone, and cisplatin) regimen; or
- As a component of high-dose cytarabine with rituximab regimen; or
B-Cell Lymphomas - Castleman's Disease (CD)
- Used for unicentric CD with or without prednisone and/or cyclophosphamide:
- For surgically unresectable disease; or
- For symptomatic disease following incomplete resection; or
- As second-line therapy for relapsed or refractory disease; or
- Therapy for active multicentric CD with no organ failure with or without prednisone for individuals who are human immunodeficiency virus-negative and human herpesvirus-8-negative:
- As primary treatment; or
- For relapsed disease; or
- If no response to primary treatment; or
- Therapy for active multicentric CD with no organ failure with or without liposomal doxorubicin and/or prednisone for individuals who are human herpesvirus-8-positive:
- As preferred** primary treatment; or
- For relapsed disease; or
- If no response to primary treatment; or
- Used with or without prednisone for active multicentric CD with no organ failure for progression greater than or equal to six (6) months following completion of rituximab; or
- Primary treatment for multicentric CD for individuals with fulminant human herpesvirus-8 with or without organ failure:
- In combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- In combination with CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen; or
- In combination with CVP (cyclophosphamide, vincristine, and prednisone) regimen; or
- In combination with Liposomal doxorubicin; or
- As a single agent if individual is not a candidate for combination therapy; or
- Treatment for refractory or progressive multicentric CD in combination with liposomal doxorubicin or with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone), or CVP (cyclophosphamide, vincristine, and prednisone) regimen:
- As initial treatment; or
- If no response to initial treatment for refractory or progressive disease; or
- Subsequent therapy for multicentric CD that has progressed following treatment of relapsed/refractory or progressive disease in combination with:
- Bortezomib; or
- Lenalidomide; or
- Thalidomide; or
B-Cell Lymphomas - Diffuse Large B-Cell Lymphoma (DLBCL)
- First-line therapy for stage I-II disease as a component of:
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- First-line therapy for stage I-II disease for individuals with poor left ventricular function as a component of:
- RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen or
- RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab; or
- RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen; or
- RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone) regimen; or
- First-line therapy for stage I-II disease for very frail individuals and individuals greater than 80 years of age with comorbidities as a component of:
- RCEPP regimen; or
- RCDOP regimen; or
- R-mini-CHOP; or
- RGCVP regimen; or
- First-line therapy for stage III-IV disease as a component of:
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab; or
- First-line therapy for stage III-IV disease in individuals with poor left ventricular function as a component of:
- RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen; or
- RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen; or
- Dose-adjusted EPOCH regimen with rituximab; or
- RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen; or
- RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone) regimen or
- First-line therapy for stage III-IV disease for very frail individuals and individuals greater than 80 years of age with comorbidities as a component of:
- RCEPP regimen; or
- RCDOP regimen; or
- R-mini-CHOP; or
- RGCVP regimen; or
- Second-line or subsequent therapy for partial response, no response, relapsed, progressive, or refractory disease in individuals with intention to proceed to transplant as a component of:
- DHAP (dexamethasone, cisplatin, and cytarabine) regimen with rituximab; or
- DHAX (dexamethasone, cytarabine, and oxaliplatin) regimen with rituximab,
- ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) regimen with rituximab; or
- GDP (gemcitabine, dexamethasone, and cisplatin or gemcitabine, dexamethasone, and carboplatin) regimen with rituximab; or
- GemOX (gemcitabine and oxaliplatin) regimen with rituximab; or
- ICE (ifosfamide, carboplatin, and etoposide) regimen with rituximab; or
- MINE (mesna, ifosfamide, mitoxantrone, and etoposide) regimen with rituximab; or
- Second-line or subsequent therapy for partial response, no response, relapsed, progressive, or refractory disease in non-candidates for transplant:
- As a single agent; or
- In combination with lenalidomide (non-germinal center lymphoma); or
- In combination with bendamustine; or
- In combination with Polatuzumab vendotin-piiq with or without bendamustine after greater than or equal to two (2) prior therapies; or
- As a component of CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine) with rituximab regimen; or
- As a component of dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) with rituximab regimen; or
- As a component of CEOP (cyclophosphamide, etoposide, vincristine, and prednisone) with rituximab regimen; or
- As a component of GDP with rituximab regimen; or
- As a component of GemOX with rituximab regimen; or
- As a component of gemcitabine and vinorelbine regimens with rituximab; or
- First-line therapy for primary mediastinal large B-cell lymphoma as a component of:
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab; or
- Dose-dense RCHOP regimen followed by ICE (ifosfamide, carboplatin, and etoposide) regimen; or
- First-line therapy for grey zone lymphoma as a component of:
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab; or
- First-line therapy for grey zone lymphoma for individuals with poor left ventricular function as a component of:
- RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen; or
- RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen; or
- Dose-adjusted EPOCH regimen with rituximab; or
- RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen; or
- RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone) regimen; or
- First-line therapy for grey zone lymphoma for very frail individuals and individuals greater than 80 years of age with comorbidities as a component of:
- RCEPP regimen; or
- RCDOP regimen; or
- R-mini-CHOP; or
- RGCVP regimen; or
- Treatment of primary cutaneous DLBCL, leg type as first-line with involved site radiation therapy or as second-line therapy (if not previously received) for solitary regional T 1-2 disease, or as firs-line therapy for generalized cutaneous, T3 disease:
- As a component of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- Treatment of primary cutaneous DLBCL, leg type as first-line with involved site radiation therapy or as second-line therapy (if not previously received) for solitary regional T 1-2 disease, or as firs-line therapy for generalized cutaneous, T3 disease in individuals with poor left ventricular function as a component of:
- RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen; or
- RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab; or
- RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen; or
- RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone) regimen; or
- Treatment of primary cutaneous DLBCL, leg type as first-line with involved site radiation therapy or as second-line therapy (if not previously received) for solitary regional T 1-2 disease, or as firs-line therapy for generalized cutaneous, T3 disease for very frail individuals and individuals greater than 80 years of age with comorbidities as a component of:
- RCEPP regimen; or
- RCDOP regimen; or
- R-mini-CHOP; or
- RGCVP regimen; or
- First-line therapy for extracutaneous primary cutaneous DLBCL, leg type as a component of:
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab; or
- First-line therapy for extracutaneous primary cutaneous DLBCL, leg type for individuals with poor left ventricular function as a component of:
- RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen; or
- RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen; or
- Dose-adjusted EPOCH regimen with rituximab; or
- RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen; or
- RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone) regimen; or
- First-line therapy for extracutaneous primary cutaneous DLBCL, leg type for very frail individuals and individuals greater than 80 years of age with comorbidities as a component of:
- RCEPP regimen; or
- RCDOP regimen; or
- R-mini-CHOP; or
- RGCVP regimen; or
B-Cell Lymphomas -Follicular Lymphoma (grade 1-2)
- First-line therapy for stage I, contiguous stage II, non-contiguous stage II disease, or for individuals with the indications for treatment with stage III or IV disease as:
- A component of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- A component of RCVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen; or
- In combination with bendamustine or lenalidomide; or
- Used as a single agent in elderly or infirm individuals when tolerability of combination chemotherapy is a concern as:
- First-line therapy for stage I, contiguous stage II, non-contiguous stage II disease, or for individuals with indications for treatment with stage III or IV disease; or
- Second-line or subsequent therapy (if not previously given as first-line) for refractory or progressive disease in individuals with indications for treatment; or
- Used in elderly or infirm individuals with indications for treatment in combination with chlorambucil or in combination with cyclophosphamide as:
- First-line therapy for stage I, contiguous stage II, non-contiguous stage II disease, or for individuals with indications for treatment with stage III or IV disease; or
- Second-line or subsequent therapy (if not previously given as first-line) for refractory or progressive disease in individuals with indications for treatment; or
- First-line therapy for stage I, contiguous stage II non-contiguous stage II disease, or for individuals with indications for treatment with stage III or IV disease as a single agent in individuals that were initially observed and have progressed with a low tumor burden; or
- First-line therapy for stage I, II pediatric-type follicular lymphoma in adults with extensive local disease who are not candidates for excision or involved site radiation therapy as a component of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) regimen; or
- Second-line or subsequent therapy for refractory or progressive disease in individuals with indications for treatment as a single agent or in combination with:
- Bendamustine (if not previously given as first-line); or
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen (if not previously given as first-line); or
- RCVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen ( if not previously given as first-line); or
- Lenalidomide (if not previously given as first line); or
- DHAP (dexamethasone, cisplatin, and cytarabine) regimen; or
- DHAX (dexamethasone, cytarabine, and oxaliplatin) regimen; or
- ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) regimen; or
- GDP (gemcitabine, dexamethasone, and cisplatin or gemcitabine, dexamethasone, and carboplatin) regimen; or
- GemOX (gemcitabine and oxaliplatin) regimen; or
- ICE (ifosfamide, carboplatin, and etoposide) regimen; or
- MINE (mesna, ifosfamide, mitoxantrone, and etoposide) regimen; or
- CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen; or
- CEOP (cyclophosphamide, etoposide, vincristine, and prednisone) regimen; or
- Gemcitabine and vinorelbine; or
- Polatuzumab vendotin-piiq with or without bendamustine; or
- Treatment of histologic transformation to DLBCL without translocations of MYC and BCL2 and/or BCL6 in individuals who have received minimal or no prior chemotherapy as a component of:
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) and rituximab regimen; or
- Treatment of histologic transformation to DLBCL without translocations of MYC and BCL2 and/or BCL6 in individuals who have received minimal or no prior chemotherapy and have poor left ventricular function as a component of:
- RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen; or
- RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab; or
- RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen; or
- RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine and prednisolone) regimen; or
- Treatment of histologic transformation to DLBCL without translocations of MYC and BCL2 and/or BCL6 in individuals who have received minimal or no prior chemotherapy and are very frail and for individuals greater than 80 years of age with comorbidities as a component of:
- RCEPP regimen; or
- RCDOP regimen; or
- R-mini-CHOP regimen; or
- RGCVP regimen; or
- Used in combination with polatuzumab vedotin-piiq with or without bendamustine as treatment of histologic transformation to DLBCL without translocations of MYC and BCL2 and/or BCL6 in individuals who have received minimal or no prior chemotherapy prior to histologic transformation and have no response or progressive disease after chemoimmunotherapy; or
- Treatment of histologic transformation to DLBCL with translocations of MYC and BCL2 and/or BCL6 in individuals who have received minimal or no prior chemotherapy as a component of:
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab; or
- HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose methotrexate and cytarabine regimen with rituximab; or
- R-CODOX-M (rituximab, cyclophosphamide, vincristine, and doxorubicin with methotrexate) regimen alternating with R-IVAC (rituximab, ifosfamide, etoposide, and cytarabine) regimen; or
- Treatment of histologic transformation to DLBCL in individuals who have received multiple lines of chemoimmunotherapy for indolent or transformed disease as a single agent or in combination with:
- Bendamustine; or
- DHAP (dexamethasone, cisplatin, and cytarabine) regimen; or
- DHAX (dexamethasone, cytarabine, and oxaliplatin) regimen; or
- ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) regimen; or
- GDP (gemcitabine, dexamethasone, and cisplatin or gemcitabine, dexamethasone, and carboplatin) regimen; or
- GemOX (gemcitabine and oxaliplatin) regimen; or
- ICE (ifosfamide, carboplatin, and etoposide) regimen; or
- MINE (mesna, ifosfamide, mitoxantrone, and etoposide) regimen; or
- CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen; or
- CEOP (cyclophosphamide, etoposide, vincristine, and prednisone) regimen; or
- Lenalidomide; or
- Gemcitabine and vinorelbine; or
- Polatuzumab vendotin-piiq with or without bendamustine; or
- First-line consolidation therapy in individuals with indications for treatment if initially treated with single-agent rituximab; or
- Maintenance therapy:
- As first-line consolidation or extended dosing in individuals initially presenting with high tumor burden (stage III, IV) who achieve a complete or partial response following treatment with RCHOP (rituximab, cyclophosphamide, doxorubicin, and prednisone) regimen or RCVP (rituximab, cyclophosphamide, vincristine and prednisone) regimen; or
- Second-line consolidation or extended dosing; or
- Can be considered for individuals with histologic transformation to DLBCL that is coexisting with extensive follicular lymphoma who achieve a complete response to chemoimmunotherapy; or
B-Cell Lymphomas - Gastric MALT Lymphoma
- Initial therapy (if involved site radiation therapy is contraindicated) as a single agent stage I1, or I2, or stage II1disease in individuals who are H-pylori-positive and t(11;18) positive or who are H-pylori-negative; or
- Treatment for individuals with indications for treatment as a component of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen, RCVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen, or in combination with bendamustine:
- As first-line therapy for stage IIE, or II2, or stage IV disease (distant nodal, advanced stage); or
- As additional therapy for stage I1, or I2, or stage II1H. pylori positive disease if repeat endoscopy shows no response or recurrence after antibiotic therapy and involved site radiation therapy (ISRT); or
- As additional therapy after ISRT or rituximab alone for stage I1, or I2, or stage II1disease that is lymphoma positive after restaging with endoscopy; or
- Used as a single agent in individuals with indications for treatment as:
- First-line therapy for stage IIE, or II2, or stage IV (distant nodal or advanced stage); or
- Additional therapy for stage I1, or I2, or stage II1H. pylori positive disease if repeat endoscopy shows no response or recurrence after antibiotic therapy and ISRT; or
- Additional therapy after involved site radiation therapy ISRT alone for stage I1, or I2, or stage II1disease that is lymphoma positive after restaging with endoscopy; or
- second-line or subsequent therapy for recurrent or progressive disease (if longer duration of remission); or
- Used in combination with lenalidomide for individuals with indications for treatment as:
- First-line therapy for stage IIE, or II2, or stage IV disease (distant nodal or advanced stage); or
- Additional therapy for stage I1, or I2, or stage II1H. pylori positive disease if repeat endoscopy shows no response or recurrence after antibiotic therapy and ISRT; or
- Additional therapy after ISRT or rituximab alone) for stage I1, or I2, or stage II1disease that is lymphoma positive after restaging with endoscopy; or
- Used as a single agent or in combination with chlorambucil or cyclophosphamide in elderly or infirm individuals with indications for treatment when tolerability of combination chemotherapy is a concern as:
- First-line therapy for stage IIE, or II2, or stage IV (distant nodal or advanced stage) disease; or
- Additional therapy for stage I1, or I2, or stage II1H. pylori positive disease if repeat endoscopy shows no response or recurrence after antibiotic therapy and ISRT; or
- Additional therapy after ISRT or rituximab alone for stage I1, or I2, or stage II1disease that is lymphoma positive after restaging with endoscopy; or
- Second-line or subsequent therapy for recurrent or progressive disease; or
- Consolidation as optional first-line extended therapy in individuals initially treated with single agent rituximab; or
- Second-line therapy or subsequent therapy for recurrent or progressive disease in individuals with indications for treatment:
- In combination with Bendamustine (not recommended if previously treated with bendamustine**); or
- As a component of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- As a component of RCVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen; or
- In combination with Lenalidomide (including for the elderly or infirm when tolerability of combination chemotherapy is a concern); or
B-Cell Lymphomas - High-Grade B-Cell Lymphomas
- Used as induction therapy for high-grade B-cell lymphomas with translocations of MYC and BCL2 and/or BCL6 (double/triple hit lymphoma) or high-grade B-cell lymphomas, not otherwise specified as a component of:
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab; or
- Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose methotrexate and cytarabine regimen with rituximab; or
- R-CODOX-M (rituximab, cyclophosphamide, vincristine, and doxorubicin with methotrexate) regimen alternating with R-IVAC (rituximab, ifosfamide, etoposide, and cytarabine) regimen; or
- Used as induction therapy for high-grade B-cell lymphomas, not otherwise specified* as a component of:
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab; or
- Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose methotrexate and cytarabine regimen with rituximab; or
- R-CODOX-M (rituximab, cyclophosphamide, vincristine, and doxorubicin with methotrexate) regimen alternating with R-IVAC (rituximab, ifosfamide, etoposide, and cytarabine) regimen; or
- Second-line or subsequent therapy for partial response, no response, relapsed, progressive, or refractory high-grade B-cell lymphomas with translocations of MYC and BCL2 and/or BCL6 (Double/Triple Hit Lymphoma) in:
- Individuals with intention to proceed to transplant as a component of DHAP (dexamethasone, cisplatin, and cytarabine), DHAX (dexamethasone, cytarabine, and oxaliplatin), ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin), GDP (gemcitabine, dexamethasone, and cisplatin or gemcitabine, dexamethasone, and carboplatin), GemOX (gemcitabine and oxaliplatin), ICE (ifosfamide, carboplatin, and etoposide), or MINE (mesna, ifosfamide, mitoxantrone, and etoposide) regimen with rituximab; or
- Non-candidates for transplant as a single agent, in combination with lenalidomide (non-germinal center lymphoma) or bendamustine, or as a component of CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine), dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), CEOP (cyclophosphamide, etoposide, vincristine, and prednisone), GDP, GemOX, or gemcitabine and vinorelbine regimen with rituximab; or
- Non-candidates for transplant in combination with polatuzumab vendotin-piiq with or without bendamustine after greater than or equal to two (2) prior therapies; or
- Second-line and subsequent therapy for partial response, no response, relapsed, progressive, or refractory high-grade B-cell lymphoma, NOS, in:
- Individuals with intention to proceed to transplant as component of DHAP, DHAX, ESHAP, GDP, gemcitabine, dexamethasone, and carboplatin, GemOx, ICE, or MINE, regimen with rituximab; or
- Non-candidates for transplant as a single agent, in combination with lenalidomide (non-germinal center lymphoma) or bendamustine, or as a coponet of CEPP, dose-adjusted EPOCH, CEOP, GDP, gemcitabine, dexamethasone, and carboplatin, GemOx, or gemcitabine and vinorelbine regimen with rituximab; or
- Non-candidates for transplant in combination with polatuzumab vevedotin-piiq with or without bendamustine; or
*RCHOP has been associated with inferior outcomes for individuals with highgrade B-cell lymphomas with translocations of MYC and BCL2 and/or BCL6 (double/triple hit lymphoma)
B-Cell Lymphomas - Nongastric MALT Lymphoma (Noncutaneous)
- First-line therapy for stage I-II disease in selected cases; or
- First-line therapy for stage IV disease or recurrent stage I-II disease in individuals with indications for treatment as a component of:
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- RCVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen; or
- Bendamustine with rituximab; or
- First-line therapy as a single agent or in combination with lenalidomide for stage IV disease or recurrent stage I-II disease in individuals with indications for treatment; or
- Used as a single agent or in combination with chlorambucil or cyclophosphamide for stage IV disease or recurrent stage I-II disease in elderly or infirm individuals with indications for treatment when tolerability of combination chemotherapy is a concern as:
- First-line therapy; or
- Second-line or subsequent therapy for recurrent or progressive disease; or
- Second-line or subsequent therapy for recurrent or progressive disease in individuals with indications for treatment in:
- Bendamustine with rituximab; or
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- RCVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen; or
- Lenalidomide with rituximab (including for the elderly or infirm when tolerability of combination chemotherapy is a concern); or
- Consolidation as optional first-line extended therapy; or
- Second-line or subsequent therapy as a single agent for recurrent or progressive disease in individuals with indications for treatment (if longer duration of remission); or
B-Cell Lymphomas - Nodal Marginal Zone Lymphoma
- Used as a single agent or in combination with chlorambucil or cyclophosphamide for stage I, contiguous stage II, non-contiguous stage II, or stage III, IV disease in elderly or infirm individuals with indications for treatment when tolerability of combination chemotherapy is a concern as:
- First-line therapy; or
- Second-line or subsequent therapy; or
- First-line therapy for stage I, contiguous stage II, non-contiguous stage II, or stage III, or IV disease in individuals with indications for treatment in combination with bendamustine or as a component of:
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- RCVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen; or
- First-line therapy as a single agent or in combination with lenalidomide for stage I, contiguous stage II, non-contiguous stage II, or stage III, IV disease in individuals with indications for treatment; or
- Second-line or subsequent therapy for refractory or progressive disease in individuals with indications for treatment:
- In combination with bendamustine (not recommended if previously treated with bendamustine); or
- In combination with lenalidomide including for the elderly or infirm when tolerability of combination chemotherapy is a concern; or
- As a component of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- As a component of RCVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen; or
- Consolidation as optional first-line extended therapy; or
- Second-line or subsequent therapy as a single agent for refractory or progressive disease in individuals with indications for treatment (if longer duration of remission); or
B-Cell Lymphomas - Histologic Transformation of Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma (DLBCL)
- Treatment of individuals who have received minimal or no prior chemotherapy as a component of:
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) and rituximab regimen; or
- Treatment of individuals who have received minimal or no prior chemotherapy and have poor left ventricular function as a component of:
- RCEPP (rituximab, cyclophosphamide, etoposide, prednisone, and procarbazine) regimen; or
- RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with rituximab; or
- RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen; or
- RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine and prednisolone) regimen; or
- Treatment of individuals who have received minimal or no prior chemotherapy and are very frail and for individuals greater than 80 years of age with comorbidities as a component of:
- RCEPP regimen; or
- RCDOP regimen; or
- R-mini-CHOP regimen; or
- RGCVP regimen; or
- Subsequent therapy for individuals who have received multiple lines of chemoimmunotherapy for indolent or transformed disease as a single agent, in combination with bendamustine, or as a component of:
- DHAP (dexamethasone, cisplatin, and cytarabine) regimen; or
- DHAX (dexamethasone, cytarabine, and oxaliplatin) regimen; or
- ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) regimen; or
- GDP (gemcitabine, dexamethasone, and cisplatin or gemcitabine, dexamethasone, and carboplatin) regimen; or
- GemOX (gemcitabine and oxaliplatin) regimen; or
- ICE (ifosfamide, carboplatin, and etoposide) regimen; or
- MINE (mesna, ifosfamide, mitoxantrone, and etoposide) regimen; or
- CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen; or
- CEOP (cyclophosphamide, etoposide, vincristine, and prednisone) regimen with rituximab; or
- Lenalidomide; or
- Gemcitabine and vinorelbine; or
- Used in combination with polatuzumab vedotin-piiq with or without bendamustine for individuals who have received multiple prior therapies including greater than or equal to two (2) lines of chemoimmunotherapy for indolent or transformed disease; or
B-Cell Lymphomas - Mantle Cell Lymphoma
- Aggressive induction therapy for stage I-II disease that had a partial response, progression, or relapse after initial treatment with involved site radiation therapy alone, or for aggressive stage II bulky, III, or IV disease, or symptomatic indolent stage II bulky, III, or IV TP53 mutation negative (Aggressive induction therapy followed by HDT/ASCR may not be appropriate for TP53 positive disease. ) disease in individuals who are candidates for high-dose therapy/autologous stem cell rescue (HDT/ASCR) as a component of:
- RDHA + platinum (rituximab, dexamethasone, cytarabine) + carboplatin, cisplatin, or oxaliplatin regimen; or
- Alternating RCHOP/RDHAP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)/(rituximab, dexamethasone, cytarabine, and cisplatin) regimen; or
- HyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose methotrexate and cytarabine regimen with rituximab; or
- Bendamustine with rituximab followed by rituximab in combination with high-dose cytarabine; or
- Aggressive induction therapy in combination with bendamustine for stage I-II disease that had a partial response, progression, or relapse after initial treatment with involved site radiation therapy alone, or for aggressive stage II bulky, III, or IV disease, or symptomatic indolent stage II bulky, III, or IV TP53 mutation negative disease (Aggressive induction therapy followed by HDT/ASCR may not be appropriate for TP53 positive disease.); or
- Less aggressive induction therapy for stage I-II disease as initial therapy (localized presentation, extremely rare), or for partial response, progression, or relapse after initial treatment with involved site radiation therapy alone, or for aggressive stage II bulky, III, or IV disease, or symptomatic indolent stage II bulky, III, or IV TP53 mutation positive disease in individuals who are not candidates for high dose therapy/autologous stem cell rescue in combination with bendamustine or lenalidomide, or as a component of
- VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone) regimen; or
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen with rituximab; or
- Less aggressive induction therapy for stage I-II disease (localized presentation, extremely rare) as initial therapy, or for partial response, progression, or relapse after initial treatment with involved site radiation therapy alone, or for aggressive stage II bulky, III, or IV TP53 mutation positive disease, or symptomatic indolent stage II bulky, III, or IV disease in individuals who are not candidates for high-dose therapy/autologous stem cell rescue as a component of:
- RBAC500 (rituximab, bendamustine, and cytarabine) regimen; or
- Modified HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) with rituximab regimen in individuals older than 65 years
- Single-agent maintenance therapy for aggressive stage II bulky, III, or IV disease, or symptomatic indolent stage II bulky, III, or IV disease following complete or very good partial response to less aggressive induction therapy or high-dose therapy with autologous stem cell rescue; or
- Second-line therapy for stage I-II disease or aggressive stage II bulky, III, or IV disease, or symptomatic indolent stage II bulky, III, or IV disease in individuals who have stable disease or partial response with substantial disease after induction therapy, or who have relapsed or progressed following prior treatment with chemoimmunotherapy:
- In combination with bendamustine (if not previously given); or
- As a component of RBAC500 (rituximab, bendamustine and cytarabine) regimen (f not previously given); or
- In combination with bortezomib; or
- As a component of DHAP (dexamethasone, cisplatin, and cytarabine) with rituximab regimen; or
- As a component of DHAOx (dexamethasone, cytarabine, and oxaliplatin) with rituximab regimen; or
- As a component of GemOx (gemcitabine, oxaliplatin) with rituximab regimen; or
- In combination with ibrutinib and lenalidomide; or
- In combination with venetoclax; or
- Second-line or subsequent therapy for stage I-II, aggressive stage II bulky, III, or IV , or symptomatic indolent stage II bulky, III, or IV disease in individuals who have stable disease or partial response with substantial disease after induction therapy, or who have relapsed or progressed following prior chemoimmunotherapy:
- In combination with ibrutinib; or
- In combination with lenalidomide; or
B-Cell Lymphomas - Pediatric Aggressive Mature B-Cell Lymphomas
- Induction therapy for individuals with greater than or equal to 20 percent reduction after COP reduction phase as a component of COG ANHL1131 regimen B/induction one (1) and two (2) with COPADM (cyclophosphamide, vincristine, prednisone, doxorubicin, methotrexate, and intrathecal therapy with methotrexate and hydrocortisone) with rituximab regimen:
- For group B individuals with low-risk disease [stage I or II individuals who are not fully resected or any stage III individual with LDH less than or equal to 2 times the upper limit of normal (ULN)]; or
- For group B individuals with high-risk disease (any stage III individual with LDH greater than two (2) times upper limit of normal (ULN), and all non-CNS stage IV individuals with less than 25 percent bone marrow involvement); or
- Consolidation therapy one (1) for individuals with greater than or equal to 20 percent reduction after COP reduction phase as a component of COG ANHL1131 regimen B with CYM (cytarabine, methotrexate, and intrathecal therapy with methotrexate, cytarabine, and hydrocortisone) with rituximab regimen:
- For group B individuals with low-risk disease [stage I or II individuals who are not fully resected or any stage III individual with LDH less than or equal to two (2) times the ULN]; or
- For group B individuals with high-risk disease (any stage III individual with LDH greater than two (2) times ULN, and all non-CNS stage IV individuals with less than 25 percent bone marrow involvement); or
- Induction therapy as a component of COG ANHL1131 regimen C1/induction one (1) and two (2) with R-COPADM (cyclophosphamide, vincristine, prednisone, doxorubicin, methotrexate, and intrathecal therapy with methotrexate, cytarabine, and hydrocortisone) with rituximab regimen for:
- Group B individuals with less than 20 percent size reduction after COP reduction phase; or
- Group C individuals with CNS negative disease after initial treatment with COP reduction phase; or
- Group C individuals with CNS positive and CSF negative or positive disease after initial treatment with COP reduction phase; or
- Alternative induction therapy as a component of COG ANHL1131 regimen C3*/induction one (1) and two (2) with R-COPADM (cyclophosphamide, vincristine, prednisone, doxorubicin, methotrexate, and intrathecal therapy with methotrexate, cytarabine, and hydrocortisone) with rituximab regimen for:
- Group C individuals with CNS and CSF positive disease; or
- Group C individuals on regimen C1 therapy with less than 20 percent size reduction after COP reduction phase; or
- Consolidation therapy one (1) and two (2) as a component of COG ANHL1131 regimen C1 with R-CYVE (cytarabine, etoposide and intrathecal therapy with methotrexate and hydrocortisone) with rituximab regimen:
- For group B individuals with less than complete response after first cycle of consolidation with CYM (cytarabine, methotrexate, and intrathecal therapy with methotrexate, cytarabine, and hydrocortisone) regimen; or
- For group C individuals with CNS negative disease; or
- For group C individuals with CNS positive disease, plus high-dose methotrexate and additional intrathecal therapy with methotrexate, cytarabine, and hydrocortisone after R-CYVE 1 only; or
- Consolidation therapy one (1) and two (2) as a component of COG ANHL1131 regimen C3 with R-CYVE (cytarabine, etoposide and intrathecal therapy with methotrexate and hydrocortisone) with rituximab regimen for group C individuals with CNS and CSF positive disease, plus high-dose methotrexate and additional intrathecal therapy with methotrexate, cytarabine, and hydrocortisone after R-CYVE one (1) only; or
- Preferred treatment for relapsed or refractory disease (if not previously received as a part of initial therapy) as a component of R-CYVE (cytarabine, etoposide, and intrathecal therapy with methotrexate and hydrocortisone) with rituximab regimen; or
- Preferred treatment for relapsed or refractory disease as a component of R-ICE (ifosfamide, carboplatin, and etoposide) with rituximab regimen; or
B-Cell Lymphomas - Post-transplant Lymphoproliferative Disorder (PTLD)
- Single-agent therapy as:
- First-line therapy for monomorphic (B-cell type) or polymorphic (B-cell type) PTLD; or
- Second-line therapy for partial response, persistent or progressive non-destructive lesions or for partial response, persistent or progressive monomorphic (B-cell type) PTLD if immunosuppressive was reduced in first-line therapy; or
- Maintenance therapy for polymorphic (B-cell type) PTLD achieving complete response on first-line therapy; or
- Concurrent chemoimmunotherapy for CD20+ disease as a component of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen with rituximab or as a component of CVP (cyclophosphamide, vincristine, and prednisone), CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine), or CEOP (cyclophosphamide, etoposide, vincristine, and prednisone) regimen with rituximab for frail individuals who cannot tolerate anthracyclines as:
- First-line therapy for monomorphic (B-cell type) or systemic polymorphic (B-cell type) PTLD; or
- Second-line therapy for partial response, persistent or progressive monomorphic (B-cell type) or polymorphic (B-cell type) PTLD; or
- Sequential chemoimmunotherapy as a single agent followed by CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen with or without rituximab as:
- First-line therapy for monomorphic (B-cell type) or systemic polymorphic (B-cell type) PTLD; or
- Second-line therapy for persistent or progressive monomorphic (B-cell type) or polymorphic (B-cell type) PTLD; or
- Used in combination with high-dose methotrexate for primary CNS PTLD (B-cell type); or
- Second-line and subsequent therapy for individuals with partial response, persistent or progressive disease after receiving chemoimmunotherapy as first-line treatment for monomorphic PTLD (B-cell type) as a single agent or in combination with:
- Bendamustine; or
- DHAP (dexamethasone, cisplatin, and cytarabine) regimen; or
- DHAX (dexamethasone, cytarabine, and oxaliplatin) regimen; or
- ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) regimen; or
- GDP (gemcitabine, dexamethasone, and cisplatin or gemcitabine, dexamethasone, and carboplatin) regimen; or
- GemOX (gemcitabine and oxaliplatin) regimen; or
- ICE (ifosfamide, carboplatin, and etoposide) regimen; or
- MINE (mesna, ifosfamide, mitoxantrone, and etoposide) regimen; or
- CEPP (cyclophosphamide, etoposide, prednisone, and procarbazine) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen; or
- CEOP (cyclophosphamide, etoposide, vincristine, and prednisone) regimen with rituximab; or
- Lenalidomide; or
- Gemcitabine and vinorelbine; or
- Polatuzumab vedotin-piiq with or without bendamustine (after greater than or equal to two (2) prior therapies; or
B-Cell Lymphoma - Primary Cutaneous
- Therapy for primary cutaneous marginal zone or follicle center lymphoma with:
- Solitary/regional, T1-2 disease that is refractory to initial therapy; or
- Generalized disease (skin only), T3 disease; or
Central nervous system cancers - Leptomeningeal metastases
- Intra-cerebrospinal fluid (CSF) treatment for leptomeningeal metastases from lymphomas for:
- Primary treatment in individuals with good risk status (KPS greater than or equal to 60, no major neurologic deficits, minimal systemic disease, and reasonable systemic treatment options if needed); or
- Maintenance treatment in individuals with negative CSF cytology or in clinically stable individuals with persistently positive CSF cytology; or
- Treatment in individuals with positive CSF cytology that have progressed after receiving prior treatment; or
Central Nervous System Cancers - Primary CNS Lymphoma:
- Induction therapy:
- In combination with high-dose methotrexate; or
- In combination with high-dose methotrexate and temozolomide; or
- As a component of R-MPV (rituximab, methotrexate, procarbazine, and vincristine) regimen; or
- In combination with high-dose methotrexate and temozolomide followed by post-RT temozolomide; or
- As a single agent if individual is unsuitable for or intolerant to high-dose methotrexate; or
- In combination with temozolomide if individual is unsuitable for or intolerant to high-dose methotrexate; or
- In combination with lenalidomide if individual is unsuitable for or intolerant to high-dose methotrexate; or
- Consider as intra-CSF therapy if CSF positive or spinal MRI positive as:
- Part of induction therapy; or
- Treatment alone or in combination with systemic chemotherapy for relapsed or refractory disease in individuals with prior WBRT; or
- Consider for consolidation therapy as continuation of induction regimen in individuals with complete response or complete response unconfirmed (CRu) to induction therapy:
- In combination with high-dose methotrexate; or
- In combination with high-dose methotrexate and temozolomide; or
- As a component of R-MPV (rituximab, methotrexate, procarbazine, and vincristine) regimen; or
- In combination with high-dose methotrexate and temozolomide followed by post-RT temozolomide; or
- Treatment as a single agent or in combination with temozolomide or lenalidomide for relapsed or refractory disease:
- May be considered in individuals who received prior whole brain radiation therapy (RT); or
- In individuals who received a prior high-dose methotrexate-based regimen without prior RT; or
- In combination with whole brain RT or involved field RT in individuals who received a prior high-dose methotrexate-based regimen without prior RT after no response or short response duration (less than 12 months) to prior regimen; or
- In individuals who received prior high-dose chemotherapy with stem cell rescue; or
- Treatment in combination with high-dose methotrexate with or without ibrutinib for relapsed or refractory disease:
- In individuals who received prior whole brain radiation; or
- In individuals who received a prior high-dose methotrexate-based regimen without prior radiation therapy (RT) and a previous long response duration (greater than or equal to 12 months) to prior regimen; or
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
- First-line therapy for disease without del(17p)/TP53 mutation in frail individuals with significant comorbidity (not able to tolerate purine analogs) or in individuals age greater than or equal 65 years and younger individuals with significant comorbidities (CrCl less than 70 ml/min) who have indications for treatment:
- In combination with high-dose methylprednisolone; or
- As a single agent; or
- First-line therapy in combination with bendamustine for disease without del(17p)/TP53 mutation in individuals greater than or equal to 65 years of age and younger individuals with or without significant comorbidities who have indications for treatment (not recommended for frail individuals) ; or
- First-line therapy for disease without del(17p)/TP53 mutation in individuals age less than 65 years without significant comorbidities who have indications for treatment:
- In combination with ibrutinib; or
- In combination with high-dose methylprednisolone; or
- As a component of PCR (pentostatin, cyclophosphamide, and rituximab) regimen; or
- First-line therapy for disease with del(17p)/TP53 mutation in combination with alemtuzumab or high-dose methylprednisolone in individuals with indications for treatment; or
- First line therapy for disease without del(17p)/TP53 mutations in individuals less than 65 years of age without significant comorbidities who have indications for treatment as a component of:
- FCR (fludarabine, cyclophosphamide, and rituximab) regimen (for individuals with IGHV mutated CLL); or
- Fludarabine and rituximab (FR) regimen [not recommended for CLL with del(11q)]; or
- Second-line and subsequent therapy for CLL/SLL without del(17p)/TP53 mutation in frail individuals with significant comorbidity or age greater than or equal to 65 years and younger individuals with significant comorbidities (creatining clearance less than 70 mL/min) who have indications for retreatment:
- In combination with idelalisib or venetoclax; or
- As a single agent in a dose-dense regimen; or
- In combination with alemtuzumab, chlorambucil. lenalidomide, or high-dose methylprednisolone; or
- As a component of reduced-dose FCR (fludarabine, cyclophosphamide, and rituximab) or reduced-dose PCR (pentostatin, cyclophosphamide, and rituximab) regimen; or
- Second-line and subsequent therapy in combination with bendamustine and with or without ibrutinib or idelalisib for CLL/SLL without del(17p)/TP53 mutation in individuals greater than or equal to 65 years of age or younger individuals with significant comorbidities (CrCl less than 70 ml/min) who have indications for retreatment (not recommended for frail individuals); or
- Second-line and subsequent therapy for CLL/SLL without del(17p)/TP53 mutation in individuals less than 65 years without significant comorbidities who have indications for retreatment:
- In combination with idelalisib or venetoclax; or
- In combination with alemtuzumab, bendamustine with or without ibrutinib or idelalisib, high-dose methylprednisolone, or lenalidomide; or
- As a component of FCR (fludarabine, cyclophosphamide, and rituximab) or PCR (pentostatin, cyclophosphamide, and rituximab) regimen; or
- Second-line and subsequent therapy for CLL/SLL with del(17p)/TP53 in individuals with indications for retreatment in combination with:
- Idelalisib or venetoclax; or
- Alemtuzumab, lenalidomide, or high-dose methylprednisolone; or
- Initial therapy for histologic (Richter's) transformation to DLBCL (clonally related or unknown clonal status) as a component of:
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) with rituximab regimen; or
- HyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) with rituximab regimen alternating with high-dose methotrexate and cytarabine regimen; or
- OFAR (oxaliplatin, fludarabine, cytarabine, and rituximab) regimen; or
Hairy Cell Leukemia
- Used in individuals with indications for treatment in combination with:
- Cladribine as initial therapy; or
- Cladribine for less than complete response or relapse within two (2) years of complete response following initial treatment with pentostatin; or
- Pentostatin for less than complete response or relapse within two (2) years of complete response following initial treatment with cladribine; or
- Cladribine or pentostatin for relapse greater than or equal to two (2) years following initial treatment; or
- Vemurafenib for progression after therapy for relapsed/refractory disease; or
- As a single agent in individuals with indications for treatment who are unable to receive purine analogs for:
- Less than complete response following initial treatment with cladribine or pentostatin; or
- Relapse; or
Hematopoietic Cell Transplantation
- For chronic graft-versus-host disease (GVHD) as additional therapy in conjunction with systemic corticosteroids following no response (steroid refractory disease) to first-line therapy options; or
Hodgkin Lymphoma - Nodular Lymphocyte-Predominant
- Primary treatment as a component of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) + rituximab, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) + rituximab, or CVP (cyclophosphamide, vinblastine, prednisolone) + rituximab for individuals 18 years of age or older:
- With involved site radiation therapy (ISRT) for stage IA or IIA disease (bulky or non-contiguous); or
- With ISRT for stage IB or IIB disease; or
- With or without ISRT for stage III-IV disease; or
- Primary treatment as a single agent for stage III or IV disease; or
- Second-line or subsequent systemic therapy (if not previously used) for progressive, relapsed, or refractory disease as a single agent, with or without ISRT; or
- May be considered as maintenance therapy for individuals treated with second-line systemic therapy with rituximab alone for progressive, relapsed, or refractory disease; or
- Second-line or subsequent systemic therapy (if not previously used) for progressive, relapsed, or refractory disease in combination with:
- DHAP (dexamethasone, cisplatin, and high-dose cytarabine); or
- ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin); or
- ICE (ifosfamide, carboplatin, and etoposide); or
- IGEV (ifosfamide, gemcitabine, and vinorelbine); or
- Bendamustine; or
- ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) + rituximab; or
- CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) + rituximab; or
- CVP (cyclophosphamide, vinblastine, prednisolone) + rituximab; or
Immune Checkpoint Inhibitor-Related Toxicities
- Management of the following immunotherapy-related toxicities:
- As additional therapy for moderate (G2), severe (G3) or life-threatening (G4) immunotherapy-related bullous dermatitis; or
- Moderate, severe, or life-threatening steroid-refractory myalgias or myositis; or
- For severe (G 3-4) myasthenia gravis in individuals refractory to plasmapheresis or intravenous immune globulin (IVIG)
- Treatment of immunotherapy-related encephalitis after viral causes have been excluded in individuals positive for autoimmune encephalopathy antibody, or who have had limited or no improvement after seven (7)-14 days on pulse-dose methylprednisolone with or without IVIG; or
Rosai-Dorfman Disease
- First-line or subsequent therapy, irrespective of mutation for nodal and immune-cytopenia diseases, as a single agent for:
- Symptomatic unresectable (bulky/site of disease) unifocal disease; or
- Symptomatic multifocal disease; or
- Relapsed/refractory disease; or
- Immunoglobulin G4 (IgG4) disease; or
Splenic Marginal Zone Lymphoma
- Therapy as a single-agent for symptomatic individuals with splenomegaly who are:
- Hepatitis C negative; or
- Hepatitis C positive with contraindications for hepatitis treatment; or
- Hepatitis C positive with no response to appropriate hepatitis treatment; or
- Used as a single agent or in combination with chlorambucil or cyclophosphamide for disease recurrence following initial management of splenomegaly in elderly or infirm individuals with indications for treatment when tolerability of combination chemotherapy is a concern as:
- First-line therapy (if treatment naive); or
- Second-line or subsequent therapy; or
- First-line therapy for disease recurrence following initial management of splenomegaly in treatment naive individuals with indications for treatment as a single agent, in combination with bendamustine, or as a component of:
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- RCVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen; or
- Used in combination with lenalidomide as first-line therapy for disease recurrence following initial treatment for splenomegaly in treatment naive individuals with indications for treatment; or
- Consolidation as optional first-line extended therapy in individuals initially treated with single agent rituximab; or
- Second-line (if prior treatment with rituximab) or subsequent therapy for disease recurrence in individuals with indications for treatment in combination with bendamustine (not recommended if previously treated with bendamustine**) , or as a component of:
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen; or
- RCVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen; or
- Second-line (if previously treated with rituximab) or subsequent therapy in combination with lenalidomide for disease recurrence in individuals with indications for treatment, including the elderly or infirm when tolerability of combination chemotherapy is a concern; or
- Second-line or subsequent therapy as a single agent for disease recurrence in individuals with indications for treatment (if previously treated with rituximab with a longer duration of remission); or
Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
- Used as a component of CaRD (carfilzomib, rituximab, and dexamethasone) regimen or in combination with ixazomib and dexamethasone:
- As primary therapy; or
- For relapse if previously used as primary therapy that was well tolerated and elicited a prolonged response; or
- Used as primary therapy, for relapse if previously used as primary therapy that was well tolerated and elicited a prolonged response, or for progressive or relapsed disease:
- In combination with bendamustine; or
- In combination with bortezomib and dexamethasone; or
- In combination with ibrutinib; or
- In combination with cyclophosphamide and dexamethasone; or
- As a single agent; or
- In combination with bortezomib; or
- In combination with cyclophosphamide and prednisone; or
- As a component of CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab) regimen; or
- In combination with cladribine or fludarabine in individuals who are not potential autologous stem cell transplant candidates; or
- As a component of FCR (fludarabine, cyclophosphamide, and rituximab) regimen in individuals who are not potential autologous stem cell transplant candidates; or
- Consider for maintenance therapy following a complete, very good partial, partial, or minor response to primary therapy if regimen included rituximab.
The use of rituximab (Rituxan) for all other indications not listed on this policy is considered experimental/investigational and therefore, not covered. Scientific evidence does not support the use for all other indications.
Procedure Codes
