B-Cell Lymphomas Treatment Regimens: Follicular Lymphoma (Grade 1-2)

B-Cell Lymphomas Treatment Regimens: Follicular Lymphoma (Grade 1-2)

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Note: All recommendations are category 2A unless otherwise indicated.

▶First Line Therapy1,a

REGIMEN

DOSING

Preferred Regimensb

Bendamustine + Obinutuzumab2-5,c-d

Day 1-2: Bendamustine 90mg/m2 IV over 10-30 minutes

Days 1,8,15 (Cycle 1): Obinutuzumab 1000mg IV, followed by:

Day 1 (Cycles 2-6): Obinutuzumab 1000mg IV.

Repeat cycle every 4 weeks for 6 cycles, followed by maintenance therapy with:

Day 1: Obinutuzumab 1000mg IV.

Repeat cycle every 8 weeks for a maximum of 2 years.

Bendamustine + Rituximab2,6-8,d-f

Days 1-2: Bendamustine 90mg/m2 IV over 10-30 minutes

Day 1: Rituximab 375mg/m2 IV.

Repeat cycle every 4 weeks for 6 cycles.

CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) + Obinutuzumab3,9-13,c,g-j

Day 1: Cyclophosphamide 750mg/m2 IV over 30 minutes

Day 1: Doxorubicin 50mg/m2 IV push

Day 1: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5-10 minutes

Days 1-5: Prednisone 100mg orally once daily

Days 1,8,15 (Cycle 1): Obinutuzumab 1,000mg IV, followed by:

Day 1(Cycles 2-6): Obinutuzumab 1,000mg IV.

Repeat cycle every 3 weeks for 6 cycles.

CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) + Rituximab6,9-12,14,15,f-j

Day 1: Cyclophosphamide 750mg/m2 IV over 30 minutes

Day 1: Doxorubicin 50mg/m2 IV push

Day 1: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5-10 minutes

Days 1-5: Prednisone 100mg orally once daily

Day 1: Rituximab 375mg/m2 IV.

Repeat cycle every 3 weeks for 6-8 cycles.

CVP (Cyclophosphamide, Vincristine, Prednisone) + Obinutuzumab3,9-13,c,g-i

Day 1: Cyclophosphamide 750mg/m2 IV over 30 minutes

Day 1: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5-10 minutes

Days 1-5: Prednisone 100mg orally once daily

Days 1,8,15 (Cycle 1): Obinutuzumab 1000mg IV, followed by:

Day 1 (Cycles 2-6): Obinutuzumab 1000mg IV.

Repeat cycle every 3 weeks for 8 cycles.

CVP (Cyclophosphamide, Vincristine, Prednisone) + Rituximab6,9-12,16-18,f-i

Day 1: Cyclophosphamide 750mg/m2 IV over 30 minutes OR

Day 1: Cyclophosphamide 1,000mg/m2 IV over 30 minutes.

Day 1: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5-10 minutes

Days 1-5: Prednisone 100mg orally once daily

Day 1: Rituximab 375mg/m2 IV.

Repeat every 3 weeks for 6-8 cycles.

Lenalidomide + Rituximab6,19-22,f,k

Days 2-22: Lenalidomide 20mg orally once daily

Days 1,8,15,22 (Cycle 1): Rituximab 375mg/m2 IV, followed by:

Day 1 (Cycles 2-6): Rituximab 375mg/m2 IV.

Repeat cycle every 4 weeks for 6 cycles, conditionally followed by:

Days 1-28: Lenalidomide 10mg once daily (for patients achieving a complete response [CR]).

Repeat cycle every 4 weeks for 12 cycles, with:

Day 1: Rituximab 375 mg/m2 IV.

Repeat cycle every 8 weeks for 6 cycles.

OR

Days 2-22: Lenalidomide 20mg orally once daily

Days 1,8,15,22 (Cycle 1): Rituximab 375mg/m2 IV, followed by:

Day 1 (Cycles 2-6): Rituximab 375mg/m2 IV

Repeat cycle every 4 weeks for 6 cycles, conditionally followed by:

Days 1-28: Lenalidomide 20mg orally once daily (for patients achieving a partial response [PR] until CR is achieved), followed by:

Days 1-28: Lenalidomide 10mg orally once daily to complete a total of 12 cycles.

Repeat cycle every 4 weeks for 3-6 cycles until complete clinical response followed by 6-9 cycles after CR achieved, with:

Day 1: Rituximab 375mg/m2 IV.

Repeat every 8 weeks for 6 cycles.

Other Recommended Regimens

Lenalidomide + Obinutuzumab (Category 2B)3,19,23,24,c,k

Days 1-21 (Cycles 1-6): Lenalidomide 20mg orally once daily

Days 1,8,15 (Cycle 1): Obinutuzumab 1000mg IV, followed by:

Day 1 (Cycles 2-6): Obinutuzumab 1000mg IV.

Repeat cycle every 4 weeks for 6 cycles, followed by:

Days 1-21 (Cycles 7-18): Lenalidomide 10mg orally once daily

Day 1 (odd numbered cycles beginning with Cycle 7): Obinutuzumab 1000mg IV.

Repeat cycle every 4 weeks for a maximum of 12 cycles, followed by:

Day 1: Obinutuzumab 1000mg IV.

Repeat cycle every 8 weeks for 6 cycles.

Rituximab (consider for low tumor burden)6,25-27,f

Days 1,8,15,22: Rituximab 375mg/m2 IV.

Administer for one 4-week cycle.

▶First-Line Therapy for Elderly or Infirm (if none of the above regimens are expected to be tolerable in the opinion of the treating physician)1,a

Preferred Regimens

Rituximab6, 25-27,f

Days 1,8,15,22: Rituximab 375mg/m2 IV.

Administer for one 4-week cycle.

Other Recommended Regimens

Chlorambucil28-30,l

Days 1-28: Chlorambucil 0.1mg/kg orally once daily.

Repeat cycle every 4 weeks.

OR

Day 1: Chlorambucil 40mg/m2 orally once daily.

Repeat cycle every 4 weeks.

Chlorambucil + Rituximab6,28,31,32,f,l

Days 1,8,15,22: Rituximab 375mg/m2 IV, with:

Day 1-42: Chlorambucil 6mg/m2 IV orally once daily.

Administer for one 6-week cycle, conditionally followed by consolidation therapy with:

Day 1: Rituximab 375mg/m2 IV, with:

Days 1-14: Chlorambucil 6mg/m2 IV orally once daily.

Repeat cycle every 4 weeks for 4 cycles (for patients who have had a response after first cycle).

Cyclophosphamide9,33,i

Days 1-28: Cyclophosphamide 50-100mg/m2 orally once daily.

Repeat cycle every 4 weeks.

Cyclophosphamide + Rituximab6,9,33,f,i

Day 1: Rituximab 375mg/m2 IV

Day 1: Cyclophosphamide 750mg/m2 IV over 30 minutes OR

Day 1: Cyclophosphamide 1000mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 6-8 cycles.

Ibritumomab tiuxetan (Category 2B)34,35,m

See NCCN B-Cell Lymphoma guidelines (Follicular Lymphoma [grade 1-2])1

▶First-Line Consolidation or Extended Dosing (optional)1,a

Preferred Regimens Following Chemoimmunotherapy

Rituximab Maintenance (Category 1; for patients initially presenting with high tumor burden)6,36-38,f

Day 1: Rituximab 375mg/m2 IV.

Repeat cycle every 8-12 weeks for 2 years.

Obinutuzumab Maintenance3-5,c

Day 1: Obinutuzumab 1000mg IV.

Repeat cycle every 8 weeks for 12 doses.

Other Recommended Regimens

Rituximab Consollidation (if initially treated with single-agent Rituximab)6,36-38,f

Day 1: Rituximab 375mg/m2 IV.

Repeat cycle every 8 weeks for 4 cycles.

Ibritumomab tiuxetan (Category 2B)34,35,m

See NCCN B-Cell Lymphoma guidelines (Follicular Lymphoma [grade 1-2])1

▶Second-Line and Subsequent Therapy1,a

Preferred Regimensb

Bendamustine + Obinutuzumab (not recommended for patients treated with prior Bendamustine)2-5,c-e,n

Day 1-2: Bendamustine 90mg/m2 IV over 10-30 minutes

Days 1,8,15 (Cycle 1): Obinutuzumab 1000mg IV, followed by:

Day 1 (Cycles 2-6): Obinutuzumab 1000mg IV.

Repeat cycle every 4 weeks for 6 cycles, followed by maintenance therapy with:

Day 1: Obinutuzumab 1000mg IV.

Repeat cycle every 8 weeks for a maximum of 2 years.

Bendamustine + Rituximab (not recommended for patients treated with prior Bendamustine)2,6-8,d-f

Days 1-2: Bendamustine 90mg/m2 IV over 10-30 minutes

Day 1: Rituximab 375mg/m2 IV.

Repeat cycle every 4 weeks for 6 cycles.

CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) + Obinutuzumab3,9-13,c,g-j,n

Day 1: Cyclophosphamide 750mg/m2 IV over 30 minutes

Day 1: Doxorubicin 50mg/m2 IV push

Day 1: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5-10 minutes

Days 1-5: Prednisone 100mg orally once daily

Days 1,8,15 (Cycle 1): Obinutuzumab 1,000mg IV, followed by:

Day 1 (Cycles 2-6): Obinutuzumab 1,000mg IV.

Repeat cycle every 3 weeks for 6 cycles.

CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) + Rituximab6,9-12,14,15,f-j

Day 1: Cyclophosphamide 750mg/m2 IV over 30 minutes

Day 1: Doxorubicin 50mg/m2 IV push

Day 1: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5-10 minutes

Days 1-5: Prednisone 100mg orally once daily

Day 1: Rituximab 375mg/m2 IV.

Repeat cycle every 3 weeks for 6-8 cycles.

CVP (Cyclophosphamide, Vincristine, Prednisone) + Obinutuzumab3,9-13,c,g-I,n

Day 1: Cyclophosphamide 750mg/m2 IV over 30 minutes

Day 1: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5-10 minutes

Days 1-5: Prednisone 100mg orally once daily

Days 1,8,15 (Cycle 1): Obinutuzumab 1000mg IV, followed by:

Day 1 (Cycles 2-6): Obinutuzumab 1000mg IV.

Repeat cycle every 3 weeks for 8 cycles.

CVP (Cyclophosphamide, Vincristine, Prednisone) + Rituximab6,9-12,16-18,f-i

Day 1: Cyclophosphamide 750mg/m2 IV over 30 minutes OR

Day 1: Cyclophosphamide 1,000mg/m2 IV over 30 minutes

Day 1: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5-10 minutes

Days 1-5: Prednisone 100mg orally once daily.

Day 1: Rituximab 375mg/m2 IV.

Repeat every 3 weeks for 6-8 cycles.

Lenalidomide + Rituximab6,19,39,f,k

Days 1-21 (Cycles 1-12): Lenalidomide 20mg orally once daily.

Day 1,8,15,22 (Cycle 1): Rituximab 375mg/m2 IV, followed by:

Day 1 (Cycles 2-5): Rituximab 375mg/m2 IV.

Repeat cycle every 4 weeks for 12 cycles.

Other Recommended Regimenso

Ibritumomab tiuxetan34,40,41,m

See NCCN B-Cell Lymphoma guidelines (Follicular Lymphoma [grade 1-2])1

Lenalidomide (if not a candidate for anti-CD20 monoclonal antibody therapy)19,42,k

Days 1-21: Lenalidomide 25mg orally once daily.

Repeat cycle every 4 weeks for 12 cycles.

Lenalidomide + Obinutuzumab3,19,23,24,c,k

Days 1-21 (Cycles 1-6): Lenalidomide 20mg orally once daily.

Days 1,8,15 (Cycle 1): Obinutuzumab 1000mg IV, followed by:

Day 1 (Cycles 2-6): Obinutuzumab 1000mg IV.

Repeat cycle every 4 weeks for 6 cycles, followed by:

Days 1-21 (Cycles 7-18): Lenalidomide 10mg orally once daily

Day 1 (odd numbered cycles beginning with Cycle 7): Obinutuzumab 1000mg IV.

Repeat cycle every 4 weeks for a maximum of 12 cycles, followed by:

Day 1: Obinutuzumab 1000mg IV.

Repeat cycle every 8 weeks for 6 cycles.

Obinutuzumab3,43,c

Days 1,8,15,22: Obinutuzumab 1000mg IV.

Administer for one 4-week cycle, conditionally followed by:

Day 1: Obinutuzumab 1,000mg IV.

Repeat cycle every 8 weeks for a maximum of 12 cycles (stable disease or objective response to therapy).

Rituximab6,25-27,f

Days 1,8,15,22: Rituximab 375mg/m2 IV.

Administer for one 4-week cycle.

▶Second-Line and Subsequent Therapy for Elderly or Infirm (if none of the above regimens are expected to be tolerable in the opinion of the treating physician)1,a

Preferred Regimens

Rituximab6,25-27,f

Days 1,8,15,22: Rituximab 375mg/m2 IV.

Administer for one 4-week cycle.

Other Recommended Regimens

Chlorambucil28-30,l

Days 1-28: Chlorambucil 0.1mg/kg orally once daily.

Repeat cycle every 4 weeks.

OR

Day 1: Chlorambucil 40mg/m2 orally once daily.

Repeat cycle every 4 weeks.

Chlorambucil + Rituximab6,28,31,32,f,l

Days 1,8,15,22: Rituximab 375mg/m2 IV, with:

Day 1-42: Chlorambucil 6mg/m2 IV orally once daily.

Administer for one 6-week cycle, followed by consolidation therapy with:

Day 1: Rituximab 375mg/m2 IV

Days 1-14: Chlorambucil 6mg/m2 IV orally once daily.

Repeat cycle every 4 weeks for 4 cycles (for patients who have had a response after first cycle).

Cyclophosphamide9,33,i

Days 1-28: Cyclophosphamide 50-100mg/m2 orally once daily.

Repeat cycle every 4 weeks.

Cyclophosphamide + Rituximab6,9,33,f,i

Day 1: Rituximab 375mg/m2 IV

Day 1: Cyclophosphamide 750mg/m2 IV over 30 minutes OR

Day 1: Cyclophosphamide 1000mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 6-8 cycles.

Ibritumomab tiuxetan (Category 2B)34,40,41,m

See NCCN B-Cell Lymphoma guidelines (Follicular Lymphoma [grade 1-2])1

▶Second-Line Consolidation or Extended Dosing (optional)1,a

Preferred Regimens

Rituximab Maintenance (Category 1)6,36-38,f

Day 1: Rituximab 375mg/m2 IV.

Repeat cycle every 12 weeks for 2 years.

Obinutuzumab Maintenance (for Rituximab-refractory disease)3-5,c

Day 1: Obinutuzumab 1000mg IV.

Repeat cycle every 8 weeks for 12 doses.

Other Recommended Regimens

• High-dose therapy with autologous stem cell rescue

• Allogeneic hematopoietic cell transplant for highly selected patients

▶Third-Line and Subsequent Therapy1,a

Preferred Regimens

Copanlisib (Relapsed/refractory after 2 prior therapies)44-46,p

Days 1,8,15: Copanlisib 60mg IV over 60 minutes.

Repeat cycle every 4 weeks.

Duvelisib (Relapsed/refractory after 2 prior therapies)47,48,q

Days 1-28: Duvelisib 25mg orally twice daily.

Repeat cycle every 4 weeks.

Idelalisib (Relapsed/refractory after 2 prior therapies)49-51,r

Days 1-28: Idelalisib 150mg orally twice daily.

Repeat cycle every 4 weeks.

Umbralisib (Relapsed/refractory after 3 prior therapies)52,53,s

Day 1: Umbralisib 800mg orally once daily.

Repeat every 4 weeks.

Tazemetostat (EZH2 mutation positive relapsed/refractory disease after 2 prior therapies; EZH2 wild type or unknown relapsed/refractory disease in patients who have no satisfactory alternative treatment options)54,55,t

Day 1: Tazemetostat 800mg orally twice daily.

Repeat cycle every 4 weeks.

Axicabtagene ciloleucel56-59

See NCCN B-Cell Lymphomas guidelines (Follicular Lymphoma [grade 1-2])1

▶Third-Line and Subsequent Therapy for Elderly or Infirm1,a

Preferred Regimens

Umbralisib (Relapsed/refractory after 3 prior regimens)52,53,s

Day 1: Umbralisib 800mg orally once daily.

Repeat cycle every 4 weeks.

▶Histologic Transformation to Diffuse Large B-Cell Lymphoma (DLBCL)1,a

Axicabtagene ciloleucel (only after ≥2 prior chemoimmunotherapy regimens)57-59,u,v

See NCCN B-Cell Lymphomas guidelines (Follicular Lymphoma [grade 1-2])1

Lisocabtagene maraleucel (only after ≥2 prior chemoimmunotherapy regimens)60,61,u,v

See NCCN B-Cell Lymphomas guidelines (Follicular Lymphoma [grade 1-2])1

Tisagenlecleucel (only after ≥2 prior chemoimmunotherapy regimens)62,63,u,v

See NCCN B-Cell Lymphomas guidelines (Follicular Lymphoma [grade 1-2])1

  a The choice of therapy requires consideration of many factors, including age, comorbidities, and future treatment possibilities (eg, HDT [high-dose therapy] with ASCR [autologous stem cell rescue]). Therefore, treatment selection is highly individualized.

  b Generally, a first-line treatment is not repeated

  c Obinutuzumab requires premedication with diphenhydramine, acetaminophen, and a corticosteroid.

  d This regimen may be associated with a risk of tumor lysis syndrome in patients with high-risk features, including extensive disease or underlying renal insufficiency.

  e Secondary malignancies have been associated with Bendamustine

  f Rituximab requires premedication with diphenhydramine and acetaminophen. Rituximab and hyaluronidase human injection for subcutaneous use may be substituted for Rituximab after patients have received the first full dose of Rituximab by intravenous infusion. The substitution cannot be made with used in combination with ibritumomab tiuxetan.

  g Myeloid growth factor therapy may be considered as primary prophylaxis based on the febrile neutropenia risk of the regimen

  h Vincristine is for intravenous use only and usually results in death or serious neurological damage if given via other routes.

  i Cyclophosphamide has been associated with secondary malignancies.

  j Doxorubicin has been associated with secondary malignancies.

  k Lenalidomide can be taken with or without food. Secondary malignancies have been associated with Lenalidomide. Participation in the risk evaluation and mitigation strategy (REMS) program is required for Lenalidomide.

  l Chlorambucil should be taken on an empty stomach. Secondary malignancies have been associated with Chlorambucil.

  m Selection of patients requires adequate marrow cellularity >15% and <25% involvement of lymphoma in bone marrow, and platelets >100000. In patients with prior autologous stem cell rescue, referral to a tertiary care center is highly recommended for ibritumomab tiuxetan.

  n Obinutuzumab is preferred in patients with Rituximab refractory disease, which includes disease progressing on or within 6 months of prior Rituximab therapy.

  o See second-line therapy for diffuse large b-cell lymphoma without regard to transplantability.

  p Copanlisib has multiple potential drug-drug and/or drug-food interactions. Review patient medical profile and drug package insert for specific drug and food interactions and recommendations.

  q Duvelisib has multiple potential drug-drug and/or drug-food interactions. Review patient medical profile and drug package insert for specific drug and food interactions and recommendations.

  r Idelalisib can be taken with or without food. Idelalisib has multiple potential drug-drug and/or drug-food interactions.

  s Umbralisib should be taken with food. Swallow tablet whole. Do not crush, break, cut, or chew tablets.

  t Tazemetostat can be taken with or without food. Tazemetostat has multiple potential drug-drug and/or drug-food interactions.

  u In patients intended to receive CAR T-cell therapy, Bendamustine should be used with caution unless after leukapheresis prior to CAR T-cell therapy, since it could impact the success of the patient’s T-cell collection.

  v Patients should have received at least one anthracycline or anthracenedione-based regimen, unless contraindicated.

References

1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V4.2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdff. Accessed July 25, 2021.

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30. Rai KR, Peterson BL, Appelbaum FR, et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000;343(24):1750-1757.

31. Martinelli G, Laszlo D, Bertonlini F, et al. Chlorambucil in combination with induction and maintenance rituximab is feasible and active in indolent non-Hodgkin’s lymphoma. Br J Haematol. 2003;123(2):271-277.

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33. Peterson BA, Petroni GA, Frizzera G, et al. Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the cancer and leukemia group B. J Clin Oncol. 2003;21(1):5-15.

34. Ibritumomab tiuxetan (Zevalin) [package insert]. East Windsor, NJ. Acrotech Biopharma LLC; September 2019.

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36. Salles G, Seymour JF, Offner F, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomized controlled trial. Lancet. 2011;377(9759):42-51.

37. Ghielmini M, Hsu Schmitz S-F, Cogliatti SB, et al. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2014;103(12):4416-4423.

38. van Oers MHJ, Van Glabbeke M, Giurgea L, et al. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin’s lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010;28(17):2853-2858.

39. Leonard JP, Trneny M, Izutsu K, et al. AUGMENT: A phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019;37(14):1188-1199.

40. Witzig TE, Flinn IW, Gordon LI, et al. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. J Clin Oncol. 2002;20(15):3262-3269.

41. Witzig TE, Gordon LI, Cabanillas F, et al. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. J Clin Oncol. 2002;20(10):2453-2463.

42. Witzig TE, Wiernik PH, Moore T, et al. Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin’s Lymphoma. J Clin Oncol. 2009;27(32):5404-5409.

43. Sehn LH, Coy A, Offner FC, et al. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non- Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015;33(10):3467-3474.

44. Copanlisib (Aliqopa) [package insert]. Whippany, NJ. Bayer HealthCare Pharmaceuticals Inc.; September 2017.

45. Dreyling M, Santoro A, Mollica L, et al. Phosphatidylinositol 3-kinase inhibition by copanlisib in relapsed or refractory indolent lymphoma. J Clin Oncol. 2017;35(35):3898-3905.

46. Dreyling M, Santoro A, Mollica L et al. Long-term efficacy and safety from the copanlisib CHRONOS-1 Study in patients with relapsed or refractory indolent B-cell lymphoma. Blood. 2018;132 (Supplement 1):1595.

47. Duvelisib (Copiktra) [package insert]. Needham, MA. Verastem, Inc.; September 2018.

48. Flinn IW, Miller CB, Ardeshna KM, et al. DYNAMO: A phase II study of duvelisib (IPI-145) in patients with refractory indolent non-Hodgkin lymphoma. J Clin Oncol. 2019;37(11):912-922.

49. Idelalisib (Zydelig) [package insert]. Foster City, CA. Gilead Sciences, Inc.; July 2014.

50. Gopal AK, Kahl BS, Wagner-Johnston ND, et al. PI3K inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370(11):1008-1018.

51. Salles G, Schuster SJ, de Vos S et al. Efficacy and safety of idelalisib in patients with relapsed, rituximab- and alkylating agent-refractory follicular lymphoma: a subgroup analysis of a phase 2 study. Haematologica. 2017;102(4):e156-e159.

52. Umbralisib (Ukoniq) [package insert]. Edison, NJ. TG Therapeutics, Inc.; February 2021.

53. Fowler NH, Samaniego F, Jurczak W, et al. Umbralisib, a dual PI3K/CK1 inhibitor in patients with relapsed or refractory indolent lymphoma. J Clin Oncol. 2021;39(15):1609-1618.

54. Tazemetostat (Tazverik) [package insert]. Cambridge, MA. Epizyme, Inc.; June 2020.

55. Morschhauser F, Tilly H, Chaidos A, et al. Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial. Lancet Oncol. 2020;21(11):1433-1442.

56. Axicabtagene ciloleucel (Yescarta) [package insert]. Cambridge, MA. Epizyme, Inc.; April 2021.

57. Jacobson C, Chavez JC, Sehgal AR, et al. Primary analysis of Zuma-5: A phase 2 study of axicabtagene ciloleucel (Axi-Cel) in patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). Blood. 2020. 136 (Supplement 1):40–41.

58. Neelapu SS, Lock FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531-2544.

59. Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single- arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019;20(1):31-42.

60. Lisocabtagene maraleucel (Breyanzi) [package insert]. Bothell, WA: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company; February 2021.

61. Abramson JS, Palomba MA, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396(10254):839-852

62. Tisagenlecleucel (Kymriah) [package insert]. East Hanover, NJ. Novartis Pharmaceuticals Corporation; December 2020.

63. Schuster SJ, Bishop MR, Tam CS et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56.

Revised 8/21; NCCN B-Cell Lymphoma Guidelines (Follicular Lymphoma [grade 1-2]) © 2021 by Haymarket Media, Inc.

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