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• Diffuse large B-cell lymphoma
• Pediatric individuals, ​​aged 6 months and older with previously untreated, advanced stage, CD20-positive disease, in combination with chemotherapy​
  
• First-line therapy for* stage I-II (exclud​ing stage II with extensive mesenteric disease) as a component of​:
• ​​RCHOP
  
• ​​Pola-R-CHP (polatuzumab vedotin-piiq, rituximab, cyclophosphamide, doxorubicin, and prednisone) regimen for stage modified International Prognostic Index (smIPI) >1
  
• ​First-line therapy for* ​stage II with extensive mesenteric disease or stage III-IV disease as a component of​:
  
• ​​​RCHOP (NCCN-preferred)​​
• Pola-R-CHP regimen for IPI ≥2 (NCCN-preferred)
• Dose-adjusted EPOCH regimen with rituximab​
• First-line therapy for stage I-IV disease in individuals with poor left ventricular function as a component of one of the following regimens:
  • RCDOP (rituximab, cyclophos​phamide, liposomal doxorubicin, vincristine, and prednisone) regimen
    
  • Dose-adjusted EPOCH regimen with rituximab
  • RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) regimen
  • RGCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone)
• First-line therapy for stage I-IV disease in very frail individuals and individuals aged more than 80 years with comorbidities as a component of one of the following regimens:
  • RCDOP  
    
  • R-mini-CHOP
  • RGCVP  
• ​First-line therapy for gray zone lymphoma as a component of one of the following:
• RCHOP (NCCN-preferred)​ 
• Dose-adjusted EPOCH regimen with rituximab
• First-line therapy for gray zone lymphoma​ in individuals with poor left ventricular function as a component of one of the following regimens:
• ​RCDOP 
• Dose-adjusted EPOCH regimen with rituximab
• RCEOP regimen with rituximab
• RGCVP 
• ​First-line therapy for gray zone lymphoma​​ in very frail individuals and individuals aged more than 80 years with comorbidities as a component of one of the following regimens:
  • RCDOP 
    
  • R-mini-CHOP
  • RGCVP
• Second-line or subsequent therapy for relapsed or refractory disease in individuals with intention to proceed to transplant, when they meet both of the following criteria:
  • One of the following conditions:
  • Relapsed disease more than 12 months after completion of first-line therapy
    
  • Primary refractory disease (partial response, no response, or progression) or ​relapsed disease less than 12 months after completion of first-line therapy​ in noncandidates for CAR T-cell therapy
  • Alternative systemic therapy (if not previously used) for relapsed/refractory disease in noncandidates for CAR T-cell therapy
  • As a component of one of the following regimens:
  • DHA (dexamethasone and cytarabine) + platinum (carboplatin, cisplatin, or oxaliplatin) regimen​ (NCCN-preferred)
  • GDP​ (NCCN-preferred)
  • Gemcitabine, dexamethasone, and carboplatin regimen (NCCN-preferred)​ 
  • ICE (NCCN-preferred)​ ​
  • ESHAP
  • GemOX (gemcitabine and oxaliplatin)
    
  • MINE
• First-line treatment of primary mediastinal large B-cell lymphoma as a component of one of the following regimens:
  • RCHOP
  • Dose-adjusted EPOCH
• First-line therapy for ​extracutaneous primary cutaneous diffuse large B-cell lymphoma, leg type
  • As a component of one of the following regimens:
    1. Dose-adjusted EPOCH ​with rituximab
    2. RCHOP ​
    3. Pola-R-CHP regimen for IPI ≥2
       
  • Individuals with poor left ventricular function as a component of one of the following regimens:
    1. RCDOP regimen
       
    2. Dose-adjusted EPOCH regimen with rituximab
    3. RCEOP regimen
    4. RGCVP
  • For very frail individuals and individuals aged more than 80 years with comorbidities as a component of one of the following regimens:
    1. RCDOP regimen
       
    2. R-mini-CHOP
    3. RGCVP
• Primary cutaneous diffuse large B-cell lymphoma, leg type, as a component of RCHOP for one of the following: 
  
• ​First-line therapy with ISRT 
• Second-line therapy (if not previously received) for solitary regional, T1-2 disease
• First-line therapy for generalized cutaneous disease (skin only) T3 
• Primary cutaneous diffuse large B-cell lymphoma, leg type in individuals with poor left ventricular function, when they meet both of the following criteria:​ 
• One of the following conditions:
• ​First-line therapy with ISRT 
• Second-line therapy (if not previously received) for solitary regional, T1-2 disease
• First-line therapy for generalized cutaneous disease (skin only) T3 
• As a component of one of the following regimens:
• ​RCDOP   
• Dose-adjusted EPOCH regimen with rituximab
• RCEOP regimen with rituximab   
• RGCVP    
• ​Primary cutaneous diffuse large B-cell lymphoma, leg type in ​very frail individuals and individuals aged older than 80 years with comorbidities, when they meet both of the following criteria:​ ​     ​
• One of the following conditions:
• ​First-line therapy with ISRT 
• Second-line therapy (if not previously received) for solitary regional, T1-2 disease
• First-line therapy for generalized cutaneous disease (skin only) T3 
• ​As a component of one of the following regimens:
• ​RCDOP   
• R-mini-CHOP​
• RGCVP    
  
• Second-line and subsequent therapy with rituximab in noncandidates for transplant, when they meet both of the following criteria:​ 
  
• One of the following conditions:
  
• Relapsed disease more than 12 months after completion of first-line therapy 
  
• ​Primary refractory disease (partial response, no response, or progression) or relapsed disease less than 12 months after completion of first-line therapy on noncandidates for CAR T-cell therapy
  
• Alternative systemic therapy (if not previously used) for relapsed/refractory disease in noncandidates for CAR T-cell therapy
  
•  As a component of one of the following regimens:
  
• Polatuzumab vedotin-piiq (with or without bendamustine) (NCCN-preferred) 
  
• As a single agent
• In combination with lenalidomide (nongerminal center diffuse large B-cell lymphoma) (regimens useful in certain circumstances outlined in NCCN guidelines)​
• Dose-adjusted EPOCH
  
• CEOP
  
• GDP
  
• Gemcitabine, dexamethasone, carboplatin
  
• GemOx  
• ​Used as clinically indicated as a bridging option until CAR T-cell product is available for individuals with primary refractory disease or relapsed disease less than 12 months after completion of first-line therapy as a component of one of the following: 
  • DHA (dexamethasone and c​ytarabine) + platinum (carboplatin, cisplatin, or oxaliplatin) regimen
    
  • Polatuzumab vedotin-piiq with or without bendamustine (consider/add bendamustine only after leukapheresis)
    
  • GDP regimen
    
  • Gemcitabine, dexamethasone, and carboplatin regimen
    
  • GemOx regimen
    
  • ICE regimen

• Follicular lymphoma, Classic​
  • First-line therapy for stage I, contiguous stage II, noncontiguous stage II disease, or for individuals with indications for treatment* with stage III or IV disease (NCCN-preferred for high tumor burden)
  • ​​As a component of RCHOP or RCVP regimen
  • In combination with bendamustine or lenalidomide ​
  • First-line therapy for stage I, contiguous stage II, noncontiguous stage II disease, or for individuals with indications for treatment* with stage III or IV disease, as a single agent (NCCN-preferred for low tumor burden)  ​
    
  • Elderly or infirm individuals, as a single agent (NCCN-preferred), when tolerability of combination chemotherapy is a concern as:
  • First-line therapy fo​r stage I, contiguous stage II, noncontiguous stage II disease, or for individuals with indications for treatment* with stage III or IV disease 
  • Second-line and subsequent therapy (if not previously given) for no response, relapsed, or progressive disease individuals with indications for treatment*
  • Elderly or infirm individuals with indications for treatment* in combination with cyclophosphamide as:
    
  • First-line therapy for stage I, contiguous stage II, noncontiguous stage II disease, or for individuals with indications for treatment* with stage III or IV disease 
    
  • Second-line and subsequent therapy (if not previously given) for no response, relapsed, or progressive disease individuals with indications for treatment*
  • Elderly or infirm individuals with indications for treatment* in combination with chlorambucil as first-line therapy for stage I, contiguous stage II, noncontiguous stage II disease, or for individuals with indications for treatment* with stage III or IV disease 
  • First-line therapy for stage I, II pediatric-type follicular lymphoma in adults with extensive local disease who are not candidates for excision or ISRT, as a component RCHOP regimen
  • Second-line or subsequent therapy (if not previously given) for no response, relapsed, or progressive disease in individuals with the indications for treatment* in one of the following regimens:
    • As a single agent (NCCN-preferred in older or infirm)  
    • Bendamustine with rituximab (NCCN-preferred)  
    • RCHOP (NCCN-preferred)       
      
    • RCVP (NCCN-preferred)          
    • Lenalidomide with rituximab (NCCN-preferred)    
  • Maintenance therapy
    • First-line extended therapy in individuals with the indications for treatment* if initially treated with single-agent rituximab​​
      
    • NCCN-preferred as first-line extended dosing for individuals initially presenting with high tumor burden (stage III,IV) who achieve a complete or partial response following treatment with RCHOP regimen or RCVP regimen
    • ​NCCN-preferred​ second-line extended dosing

• Hairy cell leukemia
  • In combination with cladribine in individuals with the indication for treatment*** for initial therapy (NCCN preferred)
  • In combination with cladribine in individuals with the indication for treatment***​ for relapse at 2 or more years if pentostatin was used as initial therapy​ (NCCN preferred)
  • In combination with pentostatin ​in individuals with the indication for treatment***​ for relapse at 2 or more years if cladribine ​was used as initial therapy​ (NCCN preferred)​
  • In combination with cladribine in individuals with the indication for treatment***​ for less than complete response or relapse within 2 years of complete response if pentostatin was used as initial therapy
    
  • In combination with pentostatin in individuals with the indication for treatment*** for less than complete response or relapse within 2 years of complete response if cladribine was used as initial therapy
  • In combination with vemurafenib in individuals with the indication for treatment*** for progression after therapy for relapsed/refractory disease​ (NCCN preferred)​
  • In combination with vemurafenib in individuals with the indication for treatment*** for​ less than complete response or relapse within 2 years of complete response if cladribine or pentostatin was used as initial therapy (NCCN preferred)
  • In combination with vemurafenib in individuals with the indication for treatment*** as initial therapy (consider for individuals unable to receive purine analogues, including frail or those with active infection)​
    
  • ​In ​combination with cladribine or pentostatin in individuals with the indication for treatment*** ​as retreatment for relapse 2 years or greater following initial treatment (NCCN preferred)
  • ​In combination with venetoclax in individuals with the indication for treatment*** for progression after therapy for relapsed/refractory disease (for individuals with disease resistant to BRAF inhibitor therapy)​
    
  • As a single agent in individuals with the indication for treatment*** for individuals who are unable to receive purine analogues for one of the following:
    • Less than complete response or relapse within 2 years following initial treatment  
    • Relapse 2 or more years following initial treatment 

• ​​​Histiocytic neoplasms (Rosai-Dorfman disease) 
• ​First-line or subsequent therapy, irrespective of mutation, for ​IgG4-related, nodal and immune-cytopenia diseases​, as a single agent, for:
• ​Symptomatic unresectable (bulky/site of disease) unifocal disease
• Symptomatic multifocal disease
• Relapsed/refractory disease

• ​​Histologic transformation of indolent lymphomas to diffuse large B-cell lymphoma ​
• Histologic transformation of follicular or marginal zone lymphoma to diffuse large B-cell lymphoma or HGBL with MYC and BCL6 and without BCL2 rearrangements after minimal or no prior therapy as a component of:
• RCHOP
• Dose-adjusted EPOCH
• Pola-R-CHP regimen for IPI ≥2​
• Histologic transformation of follicular or marginal zone lymphoma to diffuse large B-cell lymphoma or HGBL with MYC and BCL6 and without BCL2 rearrangements after minimal or no prior therapy in those with poor left ventricular function, as a component of:​
• RCDOP regimen
• Dose-adjusted EPOCH regimen with rituximab
• RCEOP regimen with rituximab
• RGCVP
• Histologic transformation of follicular or marginal zone lymphoma to diffuse large B-cell lymphoma or HGBL with MYC and BCL6 and without BCL2 rearrangements after minimal or no prior therapy in those very frail and/or aged more than 80 years with comorbidities, as a component of:
• ​RCDOP
• R-mini-CHOP regimen
• RGCVP
  
• Partial response, no response, progressive, or relapsed disease following chemoimmunotherapy for histologic transformation of follicular or marginal zone lymphoma after minimal or no prior therapy, as additional therapy 
  
• Histologic transformation of follicular or marginal zone lymphoma after multiple lines of prior therapies including two or more chemoimmunotherapy regimens for indolent or transformed disease
  
• NCCN-preferred without regard to transplant if not previously given as a component of RCHOP regimen (Note: If partial response and proceeding to transplant, consider additional systemic therapy not previously given with or without involved site RT to induce complete response prior to transplant)
  
• NCCN-preferred in individuals with intention to proceed to transplant if previously treated with an anthracycline-based regimen as a component of one of the following:
• RDHA regimen
• GDP with rituximab regimen
• Gemcitabine, dexamethasone, and carboplatin with rituximab regimen
• ICE with rituximab regimen
• NCCN-preferred in noncandidates for transplant if previously treated with anthracycline-based regimen as a component of polatuzumab vedotin-piiq with or without bendamustine and with rituximab
• Used in noncandidates for transplant as a component of one of the following:​
• CEOP with rituximab regimen
• ​​GDP with rituximab regimen
• Gemcitabine, dexamethasone, and carboplatin with rituximab regimen​
• GemOX with rituximab regimen
  
• Induction therapy for HGBLs with MYC and BCL2 with or without BCL6 rearrangements and HGBL, not otherwise specified as a component of:
• RCHOP
  
• Dose-adjusted EPOCH
• Hyper-CVAD alternating with high-dose methotrexate and cytarabine regimen with rituximab
  
• R-CODOX-M regimen alternating with R-IVAC regimen
• ​Induction therapy for HGBLs with MYC and BCL2 with or without BCL6 rearrangements and HGBL, not otherwise specified as a component of R-mini-CHOP regimen​

• ​Mantle cell lymphoma
  • ​​Aggressive induction therapy when both of the following criteria ​are met: ​
    
  • One of the following conditions:
    
  • Additional therapy for stage I-II disease following partial response, progression, or relapse after initial treatment with ISRT alone
  • Re-induction therapy for stage I-II disease (in selected cases outlined in NCCN guidelines) for relapse after initial treatment with chemoimmunotherapy
    
  • For classical or symptomatic indolent TP53 wildtype stage II bulky noncontiguous or stage III, IV disease
  • As a component of one of the following regimens: 
    
  • LyMA regimen: RDHA regimen conditionally followed by RCHOP ​for non-PET complete response (NCCN-preferred)​
  • HyperCVAD alternating with high-dose methotrexate and cytarabine regimen with rituximab (Note: rituximab + covalent BTKi (acalabrutinib, ibrutinib, or zanubrutinib) can be used as a pretreatment to limit the number of cycles of R-HyperCVAD/rituximab maintenance)
  • NORDIC (dose-intensified induction immunochemotherapy with rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone [maxi-CHOP] alternating with rituximab and high-dose cytarabine) regimen (NCCN-preferred)
    
  • ​Bendamustine with rituximab followed by rituximab ​in combination with high-dose cytarabine (NCCN-preferred)
    
  • TRIANGLE regimen: alternating RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) + ibrutinib/RDHAP (rituximab, dexamethasone, and cytarabine) + platinum (carboplatin, cisplatin, or oxaliplatin) regimen (NCCN-preferred)​
    
  • RBAC500 (rituximab, bendamustine, and cytarabine) regimen
    
  • Less-aggressive induction therapy, when they meet both of the following criteria:  
    
  • One of the following conditions:
    
  • Initial therapy for stag​e I-II disease​
  • Additional therapy for stag​e I-II disease for partial response, progression, or relapse after initial treatment with ISRT alone 
  • Re-induction therapy for stag​e I-II disease​ (in selected cases outlined in NCCN guidelines) for relapse after initial treatment with chemoimmunotherapy in those who are not suitable for aggressive therapy  
  • For classical or indolent TP53 wildtype stage II bulky noncontiguous or stage III, IV disease in those who are not suitable for aggressive therapy 
  • As a component of one of the following regimens:
  • In combination with bendamustine or lenalidomide (NCCN-preferred)​
  • VR-CAP regimen (NCCN-preferred)
  • RCHOP (NCCN-preferred) 
  • In combination with​ acalabrutinib
    
  • ​NCCN-preferred less-aggressive induction therapy classical indolent TP53 mutated stage II bulky noncontiguous or stage III, IV disease (in absence of clinical trial) with the following:
  • ​In combination with bendamustine or lenalidomide
  • VR-CAP regimen
  • RCHOP regimen​
  • In combination with acalabrutinib as less-aggressive therapy if not suitable for aggressive therapy
  • As a component of TRIANGLE regimen: alternating RCHOP + ibrutinib/RDHAP (rituximab, dexamethasone, and cytarabine) + platinum (carboplatin, cisplatin, or oxaliplatin) regimen (NCCN-preferred), if suitable for aggressive therapy
  • Maintenance therapy, in combination with ibrutinib as: ​
    
  • For complete response following aggressive induction therapy
  • Following high dose therapy/autologous stem cell rescue​
  • Maintenance therapy, as a single agent, for classical or indolent TP53 wildtype following complete response or very good partial response to less-aggressive induction therapy with BR (bendamustine and rituximab) regimen or RCHOP​
    
  • Second-line and subsequent therapy in combination with lenalidomide (NCCN-preferred) or in combination with ibrutinib for:
    
  • Stage I-II disease with partial response, relapse, or progression after prior treatment with chemoimmunotherapy
  • ​Classical or indolent TP53 wildtype stage II bulky noncontiguous or stage III, IV disease in individuals who have no response or progressive disease or partial response with substantial disease after induction therapy
  • Relapsed or refractory disease (if not previously given)​
  • ​Second-line therapy or subsequent therapy (in certain circumstances outlined in NCCN guidelines) for stage I-II disease with partial response, relapse, or progression after prior treatment with chemoimmunotherapy; or for classical or indolent stage II bulky noncontiguous or stage III, IV disease ​in those with no response or progressive disease or partial response with substantial disease after induction therapy; or for relapsed or refractory disease ​in one of the following regimens:
    
  • ​In combination with bendamustine (if not previously given)
  • RBAC500 (rituximab, bendamustine, and cytarabine) regimen​ (if not previously treated with bendamustine) 
  • ​In combination with bortezomib
    
  • RDHA (dexamethasone and cytarabine) + platinum (carboplatin, cisplatin, or oxaliplatin) + rituximab regimen (if not previously given)
  • GemOx with rituximab
  • ​In combination with venetoclax
    
    
• ​Nodal Marginal Zone Lymphoma
  • ​First-line, second-line, or subsequent therapy ​for relapsed, refractory, or progressive disease, as a single agent (NCCN-preferred) or in combination with chlorambucil or cyclophosphamide for ​the following: 
  • ​​Stage I 
  • Contiguous stage II  
  • Stage III or IV disease in elderly or infirm individuals with indications for treatment^‡ where tolerability of combination chemotherapy is a concern
  • NCCN-preferred first-line therapy for stage I, contiguous stage II, noncontiguous stage II, or stage III, IV disease in individuals with indications for treatment^‡ in one of the following regimens:
    • RCHOP
    • RCVP
    • Bendamustine with rituximab
  • First-line therapy as a single agent for stage I, contiguous stage II, noncontiguous stage II, or stage III, IV disease in individuals with indications for treatment^‡ 
    
  • NCCN-preferred second-line or subsequent therapy for relapsed, refractory, or progressive disease in individuals with indications for treatment^‡ in one of the following regimens:
    • Bendamustine with rituximab (if not previously treated with bendamustine)
      
    • RCHOP
    • RCVP
    • Lenalidomide with rituximab ​including for the elderly or infirm when tolerability of combination therapy is a concern
  • Maintenance as optional first-line extended therapy  
  • Second-line or subsequent therapy as a single agent for relapsed, refractory or progressive disease in individuals with the indications for treatment^‡​​ (if longer duration of remission)​

• Nongastric MALT lymphoma (noncutaneous)
  • First-line therapy for stage IE or contiguous IIE disease in selected cases
    
  • First-line, second-line, or subsequent therapy ​for relapsed, refractory, or progressive disease as a single agent ​(NCCN-preferred) or in combination with chlorambucil or cyclophosphamide for stage IV disease or in recurrent stage IE or contiguous stage IIE​ disease in elderly or infirm individuals with the indications for treatment**** where tolerability of combination chemotherapy is a concern
    
  • First-line therapy (NCCN-preferred) for stage IV disease or recurrent stage IE or contiguous stage IIE​ disease in individuals with the indications for treatment**** in one of the following regimens:
    • RCHOP
    • RCVP
    • Bendamustine with rituximab
  • First-line therapy as a single agent for stage IV disease or recurrent stage IE or contiguous stage IIE​ disease in individuals with the indications for treatment****  
  • Maintenance as optional first-line extended therapy   
    
  • NCCN-preferred second-line or subsequent therapy for relapsed, refractory, or for progressive disease in individuals with the indications for treatment**** in one of the following regimens:
    • Bendamustine with rituximab (if not previously given)
    • RCHOP
    • RCVP
    • In combination with lenalidomide, including for the elderly or infirm when tolerability of combination chemotherapy is a concern
  • Second-line or subsequent therapy as a single agent for relapsed, refractory, or progressive disease in individuals with the indications for treatment****​ (if longer duration of remission)

• ​​Pediatric aggressive mature B-cell lymphomas (age ≥6 months) - Burkitt Lymphoma and Diffuse Large B-cell Lymphoma
• ​​​Induction therapy for individuals with 20% or greater size reduction after COP reduction phase as a component of Children's Oncology Group (COG) Adolescent Non-Hodgkin's Lymphoma (ANHL)1131 regimen B/induction 1 and 2 with COPADM with rituximab regimen (NCCN preferred) for:
• Group B individuals with low-risk disease (unresected stage I or nonabdominal stage II individuals or any stage III individual with lactate dehydrogenase [LDH] 2 or less times the upper limit of normal [ULN])
  
• Group B individuals with high-risk disease (any stage III individual with LDH >2 times ULN, and all non-CNS stage IV individuals with <25% bone marrow involvement)
• Consolidation therapy 1 for individuals with 20% or greater size 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 (NCCN preferred) for:
  
• ​Group B individuals with low-risk disease (unresected stage I or nonabdominal stage II individuals or any stage III individual with LDH ≤2 times the ULN)
• ​Group B individuals with high-risk disease (any stage III individual with LDH >2 times ULN, and all non-CNS stage IV individuals with <25% bone marrow involvement)
• ​Induction therapy as a component of COG ANHL1131 regimen C1/induction 1 and 2 with R-COPADM with rituximab regimen (NCCN preferred) for:
• Group B individuals with <20% size reduction after COP reduction phase
• Group C individuals with CNS-negative disease after initial treatment with COP reduction phase
• Group C individuals with CNS-positive and CSF-negative or -positive disease after initial treatment with COP reduction phase
• Alternative induction therapy as a component of COG ANHL1131 regimen C3/induction 1 and 2 with R-COPADM with rituximab regimen (NCCN preferred) for: 
• ​​Group C individuals with CNS- and CSF-positive disease
• Group C individuals on regimen C1 therapy with less than 20% size reduction after COP reduction phase​
• Consolidation therapy 1 and 2 as a component of COG ANHL1131 regimen C1 with R-CYVE with rituximab regimen (NCCN preferred) for:
• Group B individuals with less than complete response after first cycle of consolidation with CYM regimen
• Group C individuals with CNS-negative disease
• 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
• ​Consolidation therapy 1 and 2 as a component of COG ANHL1131 regimen C3 with R-CYVE with rituximab regimen (NCCN preferred) 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 1 only
• As a component of R-CYVE with rituximab regimen as treatment for relapsed/refractory disease if not previously received as a part of initial therapy (NCCN preferred)
• As a component of R-ICE (ifosfamide, carboplatin, and etoposide) with rituximab regimen as treatment for relapsed/refractory disease (NCCN preferred)​​

• Post-transplantation lymphoproliferative disorder (PTLD)
• Used as clinically indicated as a bridging option until CAR T-cell product is available for individuals with primary refractory disease or relapsed disease less than12 months after completion of first-line therapy as a component of one of the following: 
• DHA regimen
• Polatuzumab vedotin-piiq with or without bendamustine (consider/add bendamustine only after leukapheresis)
• GDP regimen
• Gemcitabine, dexamethasone, and carboplatin regimen
• GemOx regimen
• ICE regimen
• ​Single-agent therapy as:
  
• First-line therapy for monomorphic (B-cell type) or polymorphic (B-cell type) PTLD
• Second-line therapy for partial response, persistent or progressive nondestructive lesions or for partial response, persistent or progressive monomorphic (B-cell type) PTLD if immunosuppressive was reduced in first-line therapy (or for those with partial response to initial treatment with rituximab monotherapy and IPI 0-2)​
• Maintenance therapy for polymorphic (B-cell type) PTLD achieving complete response on first-line therapy
• ​​Concurrent chemoimmunotherapy for CD20+ disease as a component of RCHOP, RCVP, RCEPP, or RCEOP 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
• Second-line therapy for persistent or progressive monomorphic (B-cell type) or polymorphic (B-cell type) PTLD
• Sequential chemoimmunotherapy as a single agent followed by CHOP regimen as:  ​
• ​First-line therapy for monomorphic (B-cell type) or systemic polymorphic (B-cell type) PTLD
• Second-line therapy for partial response, persistent or progressive monomorphic (B-cell type) or polymorphic (B-cell type) PTLD
• In combination with high-dose methotrexate for primary CNS PTLD (B-cell type)
• ​Second-line and subsequent therapy for individuals with monomorphic PTLD (B-cell type) for one of the following:  
• Relapsed disease less than 12 months after completion of initial treatment with chemoimmunotherapy 
  
• ​Primary refractory disease (partial response, no response, or progression) or relapsed disease less than 12 months after completion of initial treatment with chemoimmunotherapy ​in noncandidates for CAR T-cell therapy
  
• Alternative systemic therapy (if not previously used) for relapsed/refractory disease in noncandidates for CAR T-cell therapy
  
• ​​Second-line and subsequent therapy for individuals with monomorphic PTLD (B-cell type) with intention to proceed to transplant, as a component of: ​​
  
• ​DHA regimen​
• ESHAP       
  
• GDP regimen
• Gemcitabine, dexamethasone, and carboplatin regimen
  
• GemOX regimen
• ICE
• MINE
• ​Second-line and subsequent therapy for individuals with monomorphic PTLD (B-cell type) in noncandidates for transplant​ when they meet both of the following criteria:  
  
• One of the following conditions:
  
• Relapsed disease less than 12 months after completion of initial treatment with chemoimmunotherapy 
• ​Primary refractory disease (partial response, no response, or progression) or relapsed disease less than 12 months after completion of initial treatment with chemoimmunotherapy ​in noncandidates for CAR T-cell therapy​
• Alternative systemic therapy (if not previously used) for relapsed/refractory disease in noncandidates for CAR T-cell therapy
  
• ​As a component of one of the following regimens:​
  
• ​Polatuzumab vedotin-piiq with or without bendamustine 
  
• As a single agent
• In combination with lenalidomide (nongerminal center diffuse large B-cell lymphoma), or bendamustine​
  
• Dose-adjusted EPOCH regimen​ (if not previously given)
  
• CEOP​
  
• GDP
  
• GemOx
  
• Gemcitabine, dexamethasone, carboplatin

• Primary cutaneous B-cell lymphoma
  • Therapy for primary cutaneous marginal zone or follicle center lymphoma with:
  • Generalized disease (skin only), T3
  • Solitary/regional, T1-2 disease that is refractory to initial therapy  

• ​Splenic marginal zone lymphoma
  • ​Single-agent therapy (NCCN-preferred) for symptomatic individuals with splenomegaly who have one of the following features:
    • Hepatitis C negative
    • Hepatitis C positive with contraindications for hepatitis treatment
    • Hepatitis C positive with no response to appropriate hepatitis treatment
  • First-line (if treatment naive), second-line or subsequent therapy as a single agent (NCCN-preferred) or in combination with chlorambucil or cyclophosphamide in elderly or infirm individuals with the indications for treatment^† upon disease recurrence following initial treatment for splenomegaly where tolerability of combination chemotherapy is a concern
  • First-line therapy (NCCN-preferred) in treatment-naive individuals with the indications for treatment^† for ​disease recurrence following initial treatment for splenomegaly in one of the following regimens:
    • As a single agent
    • RCHOP
    • RCVP
    • Bendamustine with rituximab
  • ​Maintenance as optional first-line extended therapy in individuals  ​
  • NCCN-preferred second-line (if previously treated with rituximab) and subsequent therapy for disease recurrence in combination with lenalidomide for disease recurrence in those with indications for treatment^†, including elderly or infirm when tolerability of combination chemotherapy is a concern  
  • Second-line and subsequent therapy as a single agent for disease recurrence in those with indications for treatment^† (if previously treated with rituximab with a longer duration of remission) 
  • NCCN-preferred ​second-line (if prior treatment with rituximab) or subsequent therapy for disease recurrence in individuals with the indications for treatment^† in one of the following regimens:
    • Bendamustine with rituximab (if not previously given)​
    • RCHOP
    • RCVP

• Multiple sclerosis, relapsing-remitting, after documented failure, contraindication or intolerance to at least two other disease-modifying treatments (DMTs)  

• Myasthenia gravis
  • Refractory to previous treatments (e.g., corticosteroids, immunosuppressants, plasma exchange, IVIG, thymectomy) as demonstrated through baseline and periodic evaluation of disease status through 1) the Myasthenia Gravis Foundation of America (MGFA) clinical classification, or 2) the Myasthenia Gravis Activities of Daily Living (MG-ADL) score

• Nephrotic syndrome, including minimal change disease, in pediatric individuals when disease is refractory to corticosteroids or other immunosuppressive therapies (e.g., cyclophosphamide, cyclosporine, mycophenolate mofetil)

• Neuromyelitis optica (NMO)

• Pemphigoid diseases refractory to corticosteroids or other immunosuppressive therapies
  • Bullous pemphigoid
  • Mucous membrane pemphigoid, including ocular cicatricial pemphigoid
  • Epidermolysis bullosa acquisita

• Pemphigus diseases (i.e., pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus) as first-line or subsequent-line of treatment

• Pure red cell aplasia, refractory to other standard therapies (e.g., corticosteroids, cyclophosphamide, cyclosporine)

• Rheumatoid arthritis, active
  • In combination with methotrexate, unless documented failure, contraindication or intolerance exists, in adults with moderate-to-severe active rheumatoid arthritis who have had an inadequate response to at least a 3-month trial of one or more tumor necrosis factor (TNF)–antagonist therapies

• Scleroderma refractory to at least 3 months of corticosteroids or other immunosuppressive therapies (e.g., methotrexate, cyclophosphamide, azathioprine, mycophenolate ​mofetil)

• Sjö​gren syndrome, primary, refractory to corticosteroids and other immunosuppressive therapies (e.g., methotrexate, cyclophosphamide, azathioprine)

• ​Systemic lupus erythematosus (SLE), refractory to other immunosuppressive therapies (e.g., azathioprine, cyclophosphamide, mycophenolate mofetil)   ​

• Thrombocytopenic purpura, immune or idiopathic (ITP) when the individual has a documented platelet count <30 × 10⁹/L  

• Castleman Disease (CD)
  • As a single agent or in combination with other systemic therapies​

• Lymphoma, Hodgkin 
• ​​As a sing​le agent​​

• Lymphoma, non-Hodgkin (NHL)
  

• Chronic lymphocytic leukemia (CLL)
• With fludarabine, cyclophosphamide (FCR), for the treatment of previously untreated and previously treated CLL
• ​As a single agent or in combination with other systemic therapies​​
  
• Diffuse large B-cell lymphoma (DLBCL)
  • Previously untreated DLBCL in combination with CHOP or other anthracycline-based chemotherapy regimens
  • As a single agent or in combination with other systemic therapies  ​​
• Follicular lymphoma
• Relapsed or refractory, follicular lymphoma as a single agent
  
• Previously untreated follicular lymphoma in combination with first-line chemotherapy and, in individuals achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy
• Nonprogressing (including stable disease) follicular lymphoma as a single agent after first-line CVP chemotherapy
• Classic follicular lymphoma as a single agent or in combination with other systemic therapies 
• Gastric MALT lymphoma
  • As a single agent or in combination with other systemic therapies 
• Hairy cell leukemia
  
• As a​ single agent or in combination with other systemic therapies​
• ​High-grade B-cell lymphomas ​
  • As a single agent or in combination with other systemic therapies
• Histologic transformation of marginal zone lymphoma to diffuse large B-cell lymphoma
  • As a single agent or in combination with other systemic therapies  ​
• Mantle cell lymphoma
  
• • As a single agent or in combination with other systemic therapies
• Nodal marginal zone lymphoma
  • As a single agent or in combination with other systemic therapies 
• Nongastric MALT lymphoma (noncutaneous)
  • As a single agent or in combination with other systemic therapies ​​
• Post-transplantation lymphoproliferative disorder (PTLD)
  • As a single agent or in combination with other systemic therapies​​
• Primary cutaneous B-cell lymphomas
• ​Primary cutaneous marginal zone or follicle center lymphoma with one of the following: solitary/regional, T1-2 disease that is refractory to initial therapy​ or generalized disease (skin only), T3
• Splenic marginal zone lymphoma
  • As a single agent or in combination with other systemic therapies ​

• Anti-myelin–​associated glycoprotein (anti-MAG) antibody demyelinating neuropathy
• Autoimmune encephalitis
• Chronic inflammatory demyelinating polyneuropathy (CIDP)
• Dermatomyositis and polymyositis
• Focal and segmental glomerulosclerosis (FSGS)
• Minimal change disease in adults
• Multiple sclerosis (MS) subtypes, other than relapsing-remitting
• Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome

BILLING REQUIREMENTS  

For drugs that have more than one method of administration, the appropriate modifier must be appended to indicate the route of administration.

• To report the intravenous route of administration, append the following modifier: JA Administered Intravenously
• To report the subcutaneous route of administration, append the following modifier: JB Administered Subcutaneously

Inclusion of a code in this policy does not imply reimbursement. Eligibility, benefits, limitations, exclusions, utilization management/referral requirements, provider contracts, and Company policies apply.​