non-hodgkin's%20lymphoma
NON-HODGKIN'S LYMPHOMA

Non-Hodgkin's lymphoma is a heterogeneous group of lymphoproliferative malignancies.
It is the most common hematologic cancer.
The most common subtypes are the diffuse large B-cell and follicular lymphoma. The subtypes are based on the malignant cell's morphology, genetic features, immunohistological characteristics, and stage of maturation.

Non-hodgkin's%20lymphoma Treatment

Principles of Therapy

Indications for Initiation of Treatment in Follicular Lymphoma (FL)

  • Groupe d’Etude des Lymphomes Folliculaires (GELF) Criteria
    • ≥3 nodal sites involved, each measuring ≥3 cm in diameter
    • Any nodal/extranodal tumor mass ≥7 cm
    • Cytopenias (leukocytes <1.0 x 109/L, platelets <100 x 109/L)
    • Presence of systemic symptoms
    • Splenomegaly
    • Pleural effusion/peritoneal ascites
    • Leukemia (>5.0 x 109/L malignant cells)
  • Follicular Lymphoma International Prognostic Index (FLIPI) Criteria
    • Eastern Cooperative Oncology Group (ECOG) performance status >1
    • Serum LDH/β2-microglobulin level > upper limit of normal
    • Hemoglobin level <12 g/dL
    • ≥60 years old
    • Ann Arbor Stage III-IV
    • ≥5 nodal sites involved

Pharmacotherapy

Alkylating Agents
  • Eg Bendamustine, Chlorambucil, Cyclophosphamide, Ifosfamide, Temozolomide
  • May be used in combination with Vincristine, Prednisone, Dexamethasone, Rituximab, Procarbazine, Doxorubicin, or Fludarabine for patients with indolent noncontiguous stage II/III/IV NHL
  • Recommended as 1st line treatment for elderly patients with FL with or without Rituximab
  • Temozolomide is recommended for refractory/relapsed MF/SS with CNS involvement
  • May be given with or without corticosteroids
Bendamustine
  • May be used alone or in combination with Rituximab in the 2nd-line treatment of MCL
    • Bendamustine/Rituximab combination may be used as 2nd-line and subsequent therapy in patients with DLBCL
  • Bendamustine (+ anti-CD20 monocloncal antibody: Obinutuzumab, Ofatumumab or Rituximab) is recommended in the following:
    • 1st line treatment for CLL/SLL patients without del(17p)/TP53 mutation aged ≥65 years and younger with significant comorbidities
    • For CLL/SLL patients without del(17p)/TP53 mutation aged <65 years without signficant comorbidities
  • Alternative treatment option for 2nd-line and subsequent therapy of PTCL and ATLL
Chlorambucil
  • Treatment option for CLL/SLL patients without del(17p)/TP53 mutation who are intolerant to purine analogs or frail with significant comorbidity or aged ≥65 years and younger with significant comorbidities, given alone or in combination with Obinutuzumab
  • Recommended for relapsed/refractory MF/SS
Cyclophosphamide
  • Recommended for relapsed/refractory MF/SS 
  • Alternative 2nd-line or initial palliative intent treatment for PTCL
Anti-CD19 Chimeric Antigen Receptor (CAR) T-cell Therapy
Axicabtagene ciloleucel
  • Recommended in the 2nd-line and subsequent treatment of patients with DLBCL
  • Used in the treatment of DLBCL arising from FL and nodal MZL, after ≥2 previous chemoimmunotherapy regimens
Tisagenlecleucel
  • Recommended in the 2nd-line and subsequent treatment of DLBCL
  • Used in the treatment of DLBCL arising from FL and nodal MZL, after ≥2 previous chemoimmunotherapy regimens
Anti-CD20 Monoclonal Antibodies
Alemtuzumab
  • Recommended for relapsed/refractory MF/SS
  • Treatment option for CLL/SLL patients without del(17p)/TP53 mutation with relapsed/refractory disease 
  • Second-line and subsequent treatment option for PTCL patients who are against organ transplant, ATLL and for symptomatic management of T-PLL patients (IV route with or without Pentostatin) 
Brentuximab vedotin
  • Second-line and subsequent treatment option for PTCL, ATLL, ENKL and DLBCL patients, and systemic 1st-line therapy for patients with MF/SS
  • In combination with CHP is recommended for monomorphic (T-cell type) PTLD, 1st-line therapy of PTCL and initial therapy of ATLL
Ibritumomab tiuxetan
  • Treatment option for elderly or infirm patients who cannot tolerate 1st- and 2nd-line and subsequent therapy for FL
  • May be an option in the 1st-line consolidation/extended dosing and 2nd-line and subsequent treatment of FL and 1st- and 2nd line and subsequent treatment of MZL
Obinutuzumab
  • Recommended for FL patients in the 1st- and 2nd-line consolidation or extended dosing therapy and in the 2nd-line and subsequent treatment in combination with Bendamustine, CHOP or CVP, of patients with Rituximab-refractory disease
  • Treatment option for untreated CLL/SLL patients without del(17p) or TP53 mutation who are intolerant to purine analogs or aged ≥65 years and younger with significant comorbidities and for patients with relapsed/refractory disease regardless of age and comorbidities
  • Treatment option for untreated CLL/SLL patients with del(17p)/TP53 mutation
  • Approved for treatment-naive CLL patients in combination with Chlorambucil
Ofatumumab
  • Recommended in the following:
    • For CLL/SLL patients with or without del(17p)/TP53 mutation with relapsed/refractory disease regardless of age and comorbidities
    • As post 2nd-line maintenance therapy for patients with complete or partial response after relapsed or refractory CLL/SLL therapy
    • 2nd-line consolidation or extended dosing treatment for Rituximab-refractory disease of patients with recurrent MZL and previously treated with Bendamustine + Obinutuzumab
  • Needs further studies to be proven effective for patients with indolent noncontiguous stage II/III/IV NHL
Radio-labeled Anti-CD20 Monoclonal Antibodies
  • Eg Yttrium-90-Labeled Ibritumomab tiuxetan
  • Suggested for indolent noncontiguous stage II/III/IV NHL and indolent/aggressive recurrent NHL patients, without prior treatment, with or without bone marrow involvement
  • Studies have shown 60-80% response rate in relapsed/refractory NHL patients
Rituximab
  • First-line therapy for patients with indolent noncontiguous stage II/III/IV CD20-positive NHL
    • May be combined with other chemotherapeutic drugs (Bendamustine, Cladribine, Fludarabine, Cyclophosphamide, Vincristine, Prednisone, Doxorubicin, Mitoxantrone)
  • Recommended in the following:
    • For patients with indolent stage I and contiguous stage II NHL
      • Considered in patients with contraindications for radiotherapy, and for those unresponsive to other chemotherapeutic agents and interventions
    • 1st- and 2nd-line and subsequent treatment of patients with FL and for elderly or infirm patients who cannot tolerate other treatment regimens for FL and MZL
    • 1st- and 2nd-line consolidation or extended dosing therapy of patients with FL and as 1st-line extended therapy for MZL
    • 1st-line therapy of patients with splenic, extranodal (MALT) and nodal MZL and for the sequential chemoimmunotherapy of monomorphic (B-cell type) and polymorphic PTLD
    • Maintenance therapy of MCL patients after high-dose autologous stem cell rescue or less aggressive therapy
    • In combination with high-dose Methotrexate for primary CNS PTLD (B-cell type)
  • Treatment option in the following:
    • For CLL/SLL patients without del(17p)/TP53 mutation aged ≥65 years and younger with significant comorbidities or frail with significant comorbidity or intolerant to purine analogs
    • 1st-line therapy of patients with extranodal MALT and nodal MZL
    • 2nd-line/subsequent therapy of patients with MZL with longer duration of remission and for DLBCL
    • Refractory/relapsed HCL
  • Also recommended for patients with indolent NHL in relapse
    • Studies show a response rate of 40-50% in patients with indolent NHL
    • May also be combined with other chemotherapeutic drugs
  • Several studies have shown that maintenance therapy with Rituximab improves overall survival in FL patients
Antimetabolites (Folic acid/Purine/Pyrimidine Analogs)
  • Eg 2-Chlorodeoxyadenosine, Cladribine, Fludarabine, Gemcitabine, Methotrexate, Pentostatin, Pralatrexate
  • Recommended for patients with indolent noncontiguous stage II/III/IV NHL
  • Cladribine is a purine analog recommended for initial therapy of HCL and for relapsed/refractory disease with or without Rituximab 
  • Fludarabine may also be combined with Chlorambucil
  • Gemcitabine is recommended in the systemic 1st-line therapy of MF/SS
  • Methotrexate may be used as 2nd-line systemic therapy for patients with MF/SS a for DLBCL with CNS disease and for DLBCL with CNS disease
  • Pentostatin is a purine analog recommended for initial therapy and relapsed/refractory HCL disease with or without Rituximab and may be used as 2nd-line therapy for patients with MF/SS
  • Pralatrexate (preferred) and Gemcitabine are 2nd-line and subsequent therapies for patients with PTCL, and systemic 1st-line therapy for patients with MF/SS
    • Pralatrexate is also recommended for relapsed/refractory EKNL
Denileukin diftitox
  • Recombinant interleukin fusion toxin combination of interleukin-2 and diphtheria toxin
  • Studies have shown 25% objective response rate in aggressive B-cell NHL patients
Lenalidomide
  • Used in the 2nd-line treatment of MCL as monotherapy or in combination with Rituximab
  • Recommended in the 2nd-line and subsequent therapy of patients with ATLL and as an alternative 2nd-line and subsequent therapy for patients with PTCL
  • May be considered for maintenance therapy in high-risk CLL/SLL patients without del(17p)/TP53 mutation after 1st-line treatment
  • Treatment option for the following:
    • CLL/SLL patients without del(17p)/TP53 mutation with relapsed/refractory disease and as post 2nd-line maintenance therapy in patients with complete or partial response after relapsed/refractory treatment
    • 2nd-line and subsequent treatment of patients with FL where anti-CD20 monoclonal antibody treatment is not appropriate
    • 1st-line consolidation therapy in patients aged 60-80 years with DLBCL
Other Antineoplastic Agents
  • Eg Acalabrutinib, Belinostat, Bortezomib, Copanlisib, Duvelisib, Ibrutinib, Idelalisib, Mogamulizumab, Moxetumomab pasudotox, Nivolumab, Pembrolizumab, Romidepsin, Vemurafenib, Venetoclax, Vorinostat, Zanubrutinib
  • Belinostat has been approved for the treatment of relapsed/refractory PTCL and as an alternative 2nd-line and subsequent therapy for ATLL and relapsed/refractory EKNL
  • Bortezomib may be used alone or in combination with Rituximab as 2nd-line therapy of patients with MCL or MF/SS, as 2nd-line and subsequent therapy for PTCL patients who are against organ transplant and for ATLL
  • Mogamulizumab is recommended in the 2nd-line and subsequent therapy of patients with ATLL and systemic 1st-line therapy of MF/SS
  • Moxetumomab pasudotox is recommended for progressive HCL after relapsed/refractory treatment
  • Nivolumab monotherapy or in combination with Brentuximab vedotin is a treatment option for relapsed/refractory PBML and EKNL
  • Pembrolizumab is indicated for patients with relapsed/refractory PBML, EKNL and MF/SS
  • Romidepsin is indicated for patients with cutaneous T-cell lymphoma, 2nd-line and subsequent therapy of PTCL and 1st-line systemic therapy for patients with MF/SS or in relapsed/refractory EKNL
  • Vemurafenib is recommended in relapsed/refractory HCL and progressive disease after treatment of relapsed/refractory HCL
  • Vorinostat is recommended in the systemic 1st-line therapy of MF/SS
  • Zanubrutinib is recommended in the 2nd-line treatment of patients with MCL 
  • There are ongoing studies investigating the use of these drugs for other types of cancer
Acalabrutinib
  • Recommended for untreated CLL/SLL patients without del(17p)/TP53 mutation or with relapsed/refractory disease regardless of age and comorbidities and for CLL/SLL patients with del(17p)/TP53 mutation with relapsed/refractory disease
  • Recommended in the 2nd-line treatment of patients with MCL
Copanlisib
  • Treatment option for patients in the 2nd-line and subsequent therapy of patients with refractory/relapsed FL and MZL, after 2 previous treatments
Duvelisib
  • Recommended for CLL/SLL patients without del(17p)/TP53 mutation with relapsed/refractory disease who are frail with significant comorbidity or aged <65 years without significant comorbidities and ≥65 years and younger with significant comorbidities and those with del(17p)/TP53 mutation with relapsed/refractory disease
  • Treatment option in the 2nd-line/subsequent therapy of patients with relapsed/refractory FL and MZL, after 2 previous therapies
Ibrutinib
  • Recommended in the following:
    • Untreated CLL/SLL patients without del(17p)/TP53 mutation or with relapsed/refractory disease who are intolerant to purine analogs, frail with significant comorbidity or aged ≥65 years and younger with significant comorbidities and <65 years without significant comordities
    • Untreated CLL/SLL patients with del(17p)/TP53 mutation or with relapsed/refractory disease
    • 2nd-line systemic therapy for patients with MCL
    • 2nd-line and subsequent treatment of MZL
      • One of the preferred regimens for elderly or infirm patients who cannot tolerate other treatment regimens
  • Treatment option in the 2nd-line and subsequent treatment of non-germinal center B-cell (GCB) DLBCL and in the treatment of progressive HCL after relapsed/refractory therapy
  • Associated with transient increase in lymphocyte count, grade 2 bleeding and hypertension
Idelalisib
  • Recommended for patients with relapsed/refractory CLL/SLL with or without del(17p)/TP53 mutation regardless of age and comorbidities
  • Treatment option in the 2nd-line and subsequent therapy of patients with relapsed/refractory FL and MZL, after 2 previous treatments
Venetoclax
  • Recommended for CLL/SLL patients with or without del(17p)/TP53 mutation with relapsed/refractory disease regardless of age and comorbidities
  • Treatment option in the 2nd-line treatment of MCL
Chemotherapeutic Combinations
  • Acalabrutinib ± Obinutuzumab
    • Recommended for CLL/SLL patients without del(17p)/TP53 mutation who are intolerant to purine analogs, frail with significant comorbidity or aged ≥65 years and younger with significant comorbidity or <65 years without significant comorbidities or untreated CLL/SLL patients with del(17p)/TP53 mutation
  • Alemtuzumab ± Rituximab
    • Recommended for CLL/SLL patients without del(17p)/TP53 mutation with relapsed/refractory disease aged ≥65 years and younger with significant comorbidities or <65 years without significant comorbidities and treatment option for untreated CLL/SLL patients with del(17p)/TP53 mutation or with relapsed/refractory disease
  • Bendamustine, Bortezomib, Rituximab
    • Treatment option for relapsed/refractory MCL
  • Bendamustine + Obinutuzumab
    • Recommended in the 1st- and 2nd-line and subsequent treatment of FL
    • Recommended in the 2nd-line and subsequent treatment of MZL in patients not previously treated with Bendamustine
  • Bendamustine + Rituximab
    • Used for patients with indolent noncontiguous stage II/III/IV NHL
    • Recommended in the 1st-line and 2nd-line and subsequent treatment of patients with FL, MZL in patients without previous treatment with Bendamustine and for CLL/SLL patients without del(17p)/TP53 mutation aged without significant comorbidities and ≥65 years and younger with significant comorbidities
    • May be used with or without Ibrutinib or Idelalisib for CLL/SLL patients without del(17p)/TP53 mutation with refractory/relapsed disease regardless of age and comorbidities
    • May be used for induction and in the 2nd-line treatment of MCL and in the 2nd-line and subsequent treatment of DLBCL
  • Chlorambucil + Rituximab
    • Recommended for CLL/SLL patients without del(17p)/TP53 mutation with refractory/relapsed disease ≥65 years and younger with significant comorbidities or frail with significant comorbidity
    • Also used in the 1st- and 2nd-line and subsequent therapy for elderly or infirm patients who cannot tolerate any treatment regimens for FL and MZL 
  • CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone)
    • Recommended in the 1st-line treatment for PTCL and ATLL
    • In combination with Etoposide (CHOEP) is used in the 1st-line treatment of PTCL and ATLL
    • In combination with Obinutuzumab is recommended in the 1st- and 2nd-line/subsequent treatment of FL
    • Part of the sequential chemoimmunotherapy of monomorphic and polymorphic PTLD if PET/CT scan is negative
  • CODOX-M (Cyclophosphamide, Doxorubicin, Vincristine, intrathecal Methotrexate and Cytarabine)
    • Followed by systemic Methotrexate and Rituximab, is recommended for induction therapy of patients <60 years old with low-risk BL
    • Followed by systemic Methotrexate alternating with Ifosfamide, Cytarabine, Etoposide and intrathecal Methotrexate (IVAC) + Rituximab, is recommended for induction therapy of patients <60 years with high-risk BL
  • CVP (Cyclophosphamide, Vincristine and Prednisone/Prednisolone)
    • Patients may be given Rituximab as maintenance therapy after treatment
    • In combination with Obinutuzumab is recommended in the 1st- and 2nd-line/subsequent treatment of FL
    • Treatment option for frail patients with monomorphic (T-cell type) PTLD who are intolerant of anthracyclines
  • Cyclophosphamide ± Rituximab
    • Treatment option in the 1st- and 2nd-line and subsequent therapy of elderly or infirm patients who cannot tolerate other treatment regimens for FL and MZL
  • Cytarabine + Rituximab
    • May be used in high doses for patients with relapsed BL
  • DHAX (Dexamethasone, Cytarabine, Oxaliplatin) ± Rituximab
    • Recommended in the 2nd-line and subsequent treatment of DLBCL
  • EPOCH-R (Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin) + Rituximab (dose-adjusted)
    • Recommended in the following:
      • 1st-line treatment for patients with primary mediastinal large B-cell lymphoma (PMBL), DLBCL, PTCL, and patients with ATLL excluding Rituximab
      • Induction therapy of patients with BL in combination with intrathecal Methotrexate
    • May also be used as 1st-line treatment in patients with DLBCL with poor LV function, for 2nd-line and subsequent treatment of DLBCL and for high-grade B-cell lymphomas (HGBL)
    • May be used as induction and 2nd-line therapy for patients with BL
  • ESHAP (Etoposide, Methylprednisolone, Cytarabine, Cisplatin) ± Rituximab
    • Recommended 2nd-line and subsequent treatment of patients with DLBCL, PTCL, ATLL and EKNL with Rituximab excluded
  • FCR (Fludarabine, Cyclophosphamide and Rituximab)
    • Recommended for patients with IGHV-mutated CLL patients without del(17p)/TP53 mutation aged <65 years without significant comorbidities or those with refractory/relapsed disease <65 years without significant comorbidities and in reduced-dose for ≥65 years old and younger with significant comorbidities
  • FC (Fludarabine, Cyclophosphamide) + Ofatumumab
    • Recommended for CLL/SLL patients without del(17p)/TP53 mutation with relapsed/refractory disease aged <65 years without significant comorbidities
  • FMC (Fludarabine, Mitoxantrone, Cyclophosphamide)
    • Indicated for T-PLL followed by Alemtuzumab
  • Gemcitabine, Vinorelbine ± Rituximab
    • Treatment option in the 2nd-line and subsequent treatment of DLBCL
  • GemOx (Gemcitabine, Oxaliplatin) ± Rituximab
    • Recommended 2nd-line and subsequent treatment for patients with DLBCL, PTCL, ATLL and EKNL with Rituximab excluded
    • In combination with Pegaspargase with Rituximab excluded, is recommended in the induction therapy of EKNL
  • GDP (Gemcitabine, Dexamethasone, Cisplatin/Carboplatin) ± Rituximab
    • Recommended 2nd-line and subsequent treatment for patients with DLBCL, PTCL, ATLL and EKNL with Rituximab excluded
    • Recommended in the induction therapy of EKNL in combination with Pegaspargase (DDGP) excluding Rituximab
    • May be used in the 2nd-line treatment of BL in combination with Rituximab
  • GVD (Gemcitabine, Vinorelbine, liposomal Doxorubicin)
    • Recommended for 2nd-line and subsequent treatment of PTCL and ATLL
  • HMDP (High-dose Methylprednisolone) + Rituximab
    • Treatment option for all patients regardless of age and comorbidities with untreated CLL/SLL without del(17p)/TP53 mutation or with relapsed/refractory disease
    • Treatment option for patients with CLL/SLL with del(17p)/TP53 mutation
  • HyperCVAD (hyperfractionated Cyclophosphamide, Vincristine, Doxorubicin, Dexamethasone) + Rituximab
    • May be used as induction therapy for patients with MCL and <60 year-old patients with BL, alternating with high-dose Methotrexate and Cytarabine + Rituximab, 1st-line alternative therapy for PTCL patients, and for patients with ATLL alternating with high-dose Methotrexate and Cytarabine
  • Ibrutinib, Lenalidomide, Rituximab
    • Treatment option for refractory/relapsed MCL
  • Ibrutinib + Obinutuzumab
    • Treatment option for CLL/SLL patients without del(17p)/TP3 mutation who are frail with significant comorbidities, intolerant of purine analogs or aged ≥65 years and younger with significant comorbidities
  • Ibrutinib + Rituximab
    • Recommended in the 2nd-line treatment of patients with MCL with short response duration to previous chemoimmunotherapy
    • Treatment option for CLL/SLL patients without del(17p)/TP53 mutation aged <65 years without significant comorbidities
  • ICE (Ifosfamide, Carboplatin, Etoposide) ± Rituximab
    • May be used in the 1st-line therapy of PMBL after RCHOP regimen, as 2nd-line and subsequent therapy for patients with DLBCL, as 2nd-line therapy for patients with BL in combination with Rituximab, and 2nd-line and subsequent therapy for PTCL, ATLL and EKNL with Rituximab excluded (ICE)
  • Idelalisib + Rituximab
    • Recommended for CLL/SLL patients without del(17p)/TP53 mutation with relapsed/refractory disease who are frail with significant comorbidities or aged ≥65 years and younger with significant comorbidities or <65 years without significant comorbidities and for CLL/SLL patients with del(17p)/TP53 mutation with relapsed/refractory disease
  • Lenalidomide + Obinutuzumab
    • Treatment option in the 1st- and 2nd-line/subsequent treatment in patients with FL
  • Lenalidomide ± Rituximab
    • Recommended in the following:
      • For CLL/SLL patients with or without del(17p)/TP53 mutation with relapsed/refractory disease regardless of age and comorbidities
      • 1st- and 2nd-line/subsequent treatment of FL
      • For less aggressive induction and in the 2nd-line treatment of MCL
      • 2nd-line and subsequent treatment of MZL particulary in elderly and infirm patients who are intolerant of other treatment regimens
    • Treatment option in the 1st-line therapy of MZL and in the 2nd-line and subsequent treatment of patients with non-GCB DLBCL
  • MINE (Mesna, Ifosfamide, Mitoxantrone, Etoposide) ± Rituximab
    • Recommended 2nd-line and subsequent treatment for patients with DLBCL
  • Obinutuzumab + Chlorambucil
    • Treatment option as 1st line therapy for CLL/SLL patients without del (17p)/TP53 mutation who are frail with significant comorbidity, intolerant of purine analogs or ≥65 years and younger with significant comorbidities
  • Obinutuzumab + Venetoclax
    • Recommended 1st-line treatment for CLL/SLL patients without del(17p)/TP53 mutation who are intolerant to purine analogs or aged ≥65 years and younger with significant comorbidities and <65 years without significant comorbidities and for CLL/SLL patients with del(17p)/TP53 mutation
  • Polatuzumab vedotin ± Bendamustine ± Rituximab
    • Recommended in the 2nd-line and subsequent treatment of patients with DLBCL with ≥2 previous treatments
  • PCR (Pentostatin, Cyclophosphamide and Rituximab)
    • Treatment option for CLL/SLL patients without del(17p)/TP53 mutation aged <65 years without significant comorbidities, those with refractory/relapsed disease ≥65 years and younger with significant comorbidities (reduced-dose) and <65 years old without comorbidities
  • PEPC (Prednisone, Etoposide, Procarbazine, Cyclophosphamide) ± Rituximab
    • May be used as 2nd-line therapy in patients with MCL and as 1st-line, 2nd-line and subsequent therapy in patients with DLBCL and those with poor LV function
    • May also be used for frail patients intolerant of anthracycline with monomorphic and polymorphic PTLD
  • R-ACVBP (Rituximab, Cyclophosphamide, Doxorubicin, Vindesine, Bleomycin and Prednisone)
    • May be used for patients with aggressive stage I/contiguous stage II NHL
  • RBAC (Rituximab, Bendamustine, Cytarabine)
    • Treatment option for less aggressive induction of MCL
  • RCHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone)
    • Recommended in the 1st- and 2nd-line/subsequent treatment for patients with FL, MZL, in the 1st-line treatment of PMBL and DLBCL, and for concurrent chemoimmunotherapy of monomorphic and polymorphic PTLD
    • Recommended for aggressive induction therapy of patients with MCL, alternating with RDHAP, for less aggressive induction, and in the 2nd-line treatment of MCL
      • Dose-intensified RCHOP (maxi-CHOP) alternating with high-dose Cytarabine is recommended for aggressive induction of MCL
    • Treatment option for HGBL
    • Combination with liposomal Doxorubicin (RCDOP) may be used as 1st-line treatment in DLBCL patients with poor LV function, frail or aged >80 years old with comorbidities
    • Used for patients with aggressive stage I/contiguous stage II (4-6 cycles), indolent noncontiguous stage II/III/IV, and aggressive noncontiguous stage II/III/IV NHL
    • Studies recommend a regimen of 3-6 cycles in patients with aggressive stage I and contiguous stage II NHL when given with IF-XRT
    • Studies have shown better treatment response (increased event-free survival and overall survival) to R-CHOP as compared to CHOP in advanced-stage DLBCL >60 years
  • R-CVP (Rituximab, Cyclophosphamide, Vincristine, and Prednisone)
    • Recommended for patients with indolent noncontiguous stage II/III/IV NHL, and in the 1st- and 2nd-line/subsequent treatment of patients with FL and MZL
    • Treatment option for concurrent treatment of frail patients with monomorphic and polymorphic PLTD who are intolerant of anthracyclines
    • Addition of Gemcitabine (RGCVP) or Etoposide (RCEOP) to this combination may be used in patients as 1st-line treatment in DLBCL patients with poor LV function
      • RGCVP may also be used in patients >80 years old with comorbidities
      • RCEOP may be used as 2nd-line and subsequent therapy for patients with DLBCL and for concurrent treatment of frail patients with monomorphic and polymorphic PLTD who are intolerant of anthracyclines
  • RDHAP (Rituximab, Dexamethasone, Cytarabine) + platinum (Carboplatin, Cisplatin or Oxaliplatin)
    • Recommended for aggressive induction therapy of patients with MCL, alternating with RCHOP, as 2nd-line and subsequent therapy for patients with DLBCL, and 2nd-line and subsequent therapy for PTCL, ATLL and ENKL with Rituximab excluded (DHAP)
  • R-F (Rituximab + Fludarabine)
    • Recommended for patients with indolent noncontiguous stage II/III/IV NHL and treatment option for CLL/SLL patients without del (17p)/TP53 mutation aged <65 years without significant comorbidities
  • R-FCM (Rituximab, Fludarabine, Cyclophosphamide and Mitoxantrone)
    • Recommended for patients with indolent noncontiguous stage II/III/IV NHL
  • R-FM (Rituximab, Fludarabine and Mitoxantrone)
    • Used for patients with indolent noncontiguous stage II/III/IV NHL
  • RIVAC (Rituximab, Ifosfamide, Cytarabine, Etoposide)
    • May be used in the 2nd-line treatment of BL
  • SMILE (steroid [Dexamethasone], Methotrexate, Ifosfamide, Pegaspargase, Etoposide) (modified)
    • Recommended in the induction therapy of advanced stage EKNL
  • Venetoclax + Ibrutinib
    • Treatment option for refractory/relapsed MCL
  • Venetoclax + Rituximab
    • Recommended for CLL/SLL patients without del(17p)/TP53 mutation with relapsed/refractory disease who are frail with significant comorbidity or aged ≥65 years and younger with significant comorbidities or <65 years without significant comorbidities and patients with del(17p)/TP53 mutation with relapsed/refractory disease
  • VR-CAP (Bortezomib, Rituximab, Cyclophosphamide, Doxorubicin, Prednisone)
    • Treatment option for less aggressive induction and in the 2nd-line treatment of MCL
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