Last updated March 15, 2022

Immunotherapy for the Treatment of Lymphoma

Panel recommendations

Hodgkin Lymphoma

For the first-line therapy of stage I–II (favorable or unfavorable risk) cHL, there was consensus that patients should receive ABVD.

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For the first-line therapy of stage III–IV cHL, the panel did not reach consensus on a single preferred regimen. Options for treatment include ABVD and A-AVD.

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For the second-line treatment of cHL, there was consensus that patients should receive salvage chemotherapy or immunotherapy, and should receive autoSCT, if eligible. Treatment options for pre-autoSCT chemotherapy or immunotherapy include BV+bendamustine, ifosfamide+carboplatin+etoposide (ICE), BV+nivolumab, or BV monotherapy. The panel noted that BV is FDA-approved for consolidation treatment following autoSCT, but that the trial supporting this data only examined patients who were BV-naïve, and that BV consolidation in patients who have previously received BV is still investigational.

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For the third-line treatment of cHL, the panel did not reach consensus on a single preferred regimen. Options for treatment include salvage chemotherapy or immunotherapy+autoSCT (if transplant-eligible), PD-1 inhibitor therapy, or BV, depending on prior therapies received and patient status.

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Non-Hodgkin Lymphoma

Diffuse Large B-cell Lymphoma

There was consensus that the first-line regimen for newly diagnosed DLBCL in adult patients should be R-CHOP.

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For pediatric patients with newly diagnosed DLBCL, there was consensus that first-line treatment should consist of rituximab with French-American-British (FAB) backbone chemotherapy.

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For the second-line therapy of DLBCL, there was consensus that transplant-eligible patients should receive a chemoimmunotherapy regimen that includes rituximab (such as rituximab+ICE (R-ICE) or rituximab+dexamethsone+cytarabine+cisplatin (R-DHAP)), followed by autoSCT consolidation if CR is achieved.

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In transplant-eligible patients who receive salvage therapy and exhibit PR, the panel did not reach consensus on a preferred consolidation regimen. Options include anti-CD19 CAR T cell therapy or autoSCT.

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For second-line therapy of DLBCL in patients who are transplant-ineligible, the panel did not reach consensus on a salvage chemotherapy or immunotherapy regimen. Treatment options include lenalidomide, lenalidomide+tafasitamab-cxix, polatuzumab vedotin-piiq+BR or an appropriate salvage chemoimmunotherapy regimen (including R-GemOx or R-GDP).

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There was consensus that the third-line treatment for DLBCL in fit patients should be anti-CD19 CAR T cell therapy (axicabtagene ciloleucel or tisagenlecleucel).

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There was consensus that patients who are ineligible for third-line anti-CD19 CAR T cell therapy should instead receive polatuzumab vedotin-piiq+BR.

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Mantle Cell Lymphoma

The panel did not reach consensus on first-line treatment for patients with MCL who are eligible for transplant. Options include chemoimmunotherapy with autoSCT or chemoimmunotherapy alone. The standard of care for first-line MCL treatment includes an anti-CD20 mAb as part of the chemoimmunotherapy regimen.

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Patients who receive autoSCT for MCL should also receive rituximab maintenance.

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For transplant-ineligible patients with MCL, there was consensus that first-line treatment should consist of an appropriate chemoimmunotherapy regimen with rituximab as maintenance therapy.

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The panel did not reach consensus on second-line or later lines of treatment for patients with MCL. Treatment options include brexucabtagene autoleucel, proteasome inhibitors, BTK inhibitors, BTK inhibitors+rituximab, or lenalidomide+rituximab.

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Follicular Lymphoma

The panel did not reach consensus on a preferred treatment for patients with low tumor burden FL (once treatment is indicated). Treatment options include rituximab monotherapy, lenalidomide+rituximab, or chemoimmunotherapy (eg, R-CHOP or BR).

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In patients with high tumor burden FL, there was consensus that first-line treatment should consist of an appropriate chemoimmunotherapy regimen (eg, R-CHOP or BR).

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There was consensus that second-line (or later) treatment regimens for patients with FL will vary, and should be decided on a case-by-case basis using factors that include prior therapies, time of relapse, tumor bulk, age, and comorbidity status. Ibritumomab tiuxetan may be used in this context, if deemed appropriate.

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  • There was consensus that when anti-CD20 antibody therapy is indicated, rituximab should be used over obinutuzumab when possible, since obinutuzumab has not demonstrated an OS benefit in comparison to rituximab.

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In patients who have been treated with rituximab, if relapse occurs less than 6 months after the last dose of rituximab, there was consensus that obinutuzumab should be used (if anti-CD20 antibody therapy is indicated). If relapse occurs more than 6 months after the last dose of rituximab, there was consensus that rituximab should be administered again (if anti-CD20 antibody therapy is indicated).

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Marginal Zone Lymphoma

There was consensus that first-line treatment of advanced stage, low tumor burden MZL should consist of rituximab monotherapy.

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There was consensus that first-line treatment of advanced stage, high tumor burden MZL should consist of an appropriate chemoimmunotherapy regimen.

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There was consensus that second-line (or later) treatment regimens for patients with MZL will vary, and should be decided on a case-by-case basis using factors that include prior therapies, time of relapse, tumor bulk, age, and comorbidity status.

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Primary Mediastinal B-cell Lymphoma

There was consensus that first-line treatment of PMBCL should consist of DA-R-EPOCH.

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There was consensus that second-line treatment of PMBCL should be identical to the recommendations listed for DLBCL (see earlier).

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The panel did not reach consensus on a specific treatment regimen for the third-line treatment of PMBCL. Treatment options include axicabtagene ciloleucel, BV+pembrolizumab, or appropriate salvage chemotherapy regimens.

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Burkitt’s Lymphoma

There was consensus that first-line treatment of BL in children, adolescents, and young adults should consist of a rituximab-containing chemoimmunotherapy regimen, either rituximab+FAB chemotherapy backbone or rituximab+Berlin-Frankfurt-Münster (BFM) chemotherapy backbone.

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There was consensus that second-line treatment of BL in children, adolescents, and young adults should consist of a rituximab-containing chemoimmunotherapy regimen (eg, R-ICE or rituximab, cytarabine, etoposide (R-CYVE)).

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There was consensus that children, adolescents, and young adults who achieve PR or CR should receive stem cell transplantation as consolidation therapy (if eligible). In the event of prior bone marrow involvement, allogeneic stem cell transplant (alloSCT) is indicated, whereas autoSCT is recommended in all other cases.

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There was consensus that first-line treatment of BL in adults should consist of a rituximab-containing chemoimmunotherapy backbone. Options include rituximab+Lymphome Malins de Burkitt (R-LMB), rituximab+cyclophosphamide+doxorubicin+methotrexate / ifosfamide+etoposide+cytarabine (R-CODOXM/IVAC), DA-R-EPOCH, rituximab+ German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia Protocol (R-GMALL), and rituximab+cyclophosphamide+vincristine+doxorubicin+dexamethasone alternating with rituximab+methotrexate+cytarabine (R-HyperCVAD).

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There was consensus that second-line treatment of BL in adults should consist of rituximab-containing chemoimmunotherapy regimens similar to those recommended for the first-line treatment of BL, with consolidation being identical to recommendations for consolidation in patients with DLBCL.

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T-cell Lymphoma

The panel did not reach consensus on a single recommended regimen for the first-line treatment of CD30+ PTCL. Treatment options include BV with cyclophosphamide+doxorubicin+prednisone (CHP), chemotherapy alone, or chemotherapy+autoSCT (if eligible).

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There was consensus that first-line treatment for CD30-negative PTCL should consist of an appropriate chemotherapy regimen+autoSCT.

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The panel did not reach consensus on a single recommended regimen for second-line treatment of PTCL in patients eligible for stem cell transplant. Treatment options include chemotherapy+autoSCT, chemotherapy+alloSCT, or HDAC inhibitors.

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There was consensus that second-line treatment for CD30+ PTCL in patients ineligible for stem cell transplant should consist of BV, up to 16 total doses.

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There was consensus that second-line treatment for CD30-negative PTCL should consist of HDAC inhibitors.

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Patients with anaplastic large cell lymphoma that is anaplastic lymphoma kinase-positive (ALK+) should not receive autoSCT.

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The panel did not reach consensus on a single recommended regimen for the first-line treatment of cutaneous TCL. Treatment options include BV, HDAC inhibitors, and an appropriate chemotherapy regimen.

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The panel did not reach consensus on a single recommended regimen for the second-line treatment of cutaneous TCL. Treatment options include HDAC inhibitors, an appropriate chemotherapy regimen (such as pralatrexate), and BV.

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Post-transplant Lymphoproliferative Disorder

The panel did not reach consensus on a preferred regimen for the treatment of B cell PTLD. Treatment options include the withdrawal of immunosuppression, rituximab, appropriate chemoimmunotherapy regimens, and antiviral agents.

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The panel did not reach consensus on a preferred regimen for the treatment of T cell PTLD. Treatment options include the withdrawal of immunosuppression, appropriate chemotherapy regimens, HDAC inhibitors, and antiviral agents.

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Chronic Lymphocytic Leukemia

The panel did not reach consensus on preferred regimens for the first-line or second-line treatment of CLL. Options include targeted therapy (if eligible) and chemoimmunotherapy regimens, which may include rituximab, obinutuzumab, ofatumumab, and alemtuzumab.

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Integration of Hematopoietic Stem Cell Transplant and Immunotherapies

There was consensus that ICI and CAR T cell therapy are both acceptable after a patient has received autoSCT. The panel did not reach consensus on the subject of whether ICIs or CAR T cell therapy should be administered prior to autoSCT.

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There was consensus that CAR T cell therapy is safe and could be considered following alloSCT, if the patient does not have active GVHD or require immunosuppression. Caution should also be exercised for patients with a history of severe GVHD.

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The panel did not reach consensus on the subject of whether ICIs should be considered contraindicated before or after alloSCT.

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Patient Considerations for Immunotherapy in the Treatment of Lymphoma

There was consensus that patients with an existing autoimmune disorder that requires immunosuppressive therapy should not receive ICIs.

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The panel did not reach consensus on the subject of whether patients with active bacterial infections should receive ICI therapy. There was consensus that patients with active bacterial infections should not receive CAR T therapy, autoSCT, or alloSCT.

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The panel did not reach consensus on the subject of whether patients with active viral infections should receive ICI therapy or autoSCT. There was consensus that patients with active viral infections should not receive CAR T therapy or alloSCT.

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Patients with HIV and lymphoma should be considered for immunotherapy, provided that their HIV infection is well controlled.

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Patients should be evaluated for HBV and HCV prior to initiating immunotherapy. If patients are positive for HBV or HCV, immunotherapy may be considered provided that an appropriate antiviral is initiated.

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There was consensus that patients with active inflammatory disorders should not receive CAR T cell therapy.

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There was consensus that elderly patients should be considered for immunotherapy and for stem cell transplant.

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Patient Support and Quality of Life Issues

There was consensus that patient reporting on toxicity and QOL issues should be emphasized for patients receiving immunotherapy, and that these patients should receive educational tools regarding immunotherapy and these potential issues.

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There was consensus that financial burden influences the availability and scheduling of immunotherapy treatments. Insurance coverage was noted as a major financial barrier.

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There was consensus that the extended time needed for cell therapy manufacturing and high financial burden are likely to impair clinical trials of cell-based therapies, such as CAR T cell therapy.

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Recommendation Grading

Overview

Title

Immunotherapy for the Treatment of Lymphoma

Authoring Organization

Publication Month/Year

January 1, 2021

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Male, Adult

Health Care Settings

Ambulatory, Emergency care, Hospital

Intended Users

Social worker, physician, nurse, nurse practitioner, physician assistant

Scope

Treatment

Diseases/Conditions (MeSH)

D008223 - Lymphoma

Keywords

lymphoma, Hodgkin lymphoma, non-Hodgkin lymphoma