B-Cell Lymphoma Treatment & Management

Updated: Mar 31, 2023
  • Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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Approach Considerations

Treatment of B-cell lymphoma varies according to the disease type. See Guidelines for first- and second-line treatment recommendations. 

Chimeric antigen receptor (CAR) T-Cell therapy

In CAR T-cell therapy, the patient's own T-cells are genetically engineered to express a specific CAR; in the case of B-cell lymphoma, this is typically CD19. After a blood sample has been obtained from the patient, the CAR molecule is introduced into the patient’s T cells through viral or nonviral approaches. The cells undergo a brief round of expansion in the laboratory and are then infused back into the patient.

The infused T cells become activated when they recognize the target antigen on the surface of the tumor. Once activated, the T cells undergo massive expansion in the body, proliferating and producing multiple different cytokines. These cytokines improve the T cells’ function, helping them traffic to the tumor site and start killing the tumor cells by expressing cytotoxic molecules (eg, granzymes and perforins).

Cytokine release syndrome is a potentially life-threatening adverse effect of CAR T-cell therapy. Tocilizumab is approved for the treatment of   severe or life-threatening cytokine release syndrome induced by CAR T-cell therapy. [17]

For full discussion of CAR T-cell therapy, see Cancer Immunotherapy with Chimeric Antigen Receptor (CAR) T-Cells

Axicabtagene ciloleucel 

In 2017, the US Food and Drug Administration (FDA) approved axicabtagene ciloleucel (Yescarta), a CD19-directed CAR T-cell therapy, for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after at least two other lines of systemic treatment have failed. It is not indicated for the treatment of patients with primary central nervous system lymphoma.

FDA approval was based on results from the ZUMA-1 study, an open-label, multicenter trial that enrolled 111 patients from 22 institutions. Study patients received the target dose of axicabtagene ciloleucel (2 × 106 cells/kg) after low-dose conditioning with cyclophosphamide and fludarabine for 3 days. The modified intention-to-treat population involved 101 patients who received axicabtagene ciloleucel. In adults with R/R DLBCL, the response rates were approximately 60-80%, with complete responses seen in 40-70% of patients. After receiving axicabtagene ciloleucel, 40% of patients maintained their complete response at 6-month follow-up. [18, 19]

The trial had a median survival follow-up of 8.7 months. Common adverse reactions included cytokine release syndrome, hypotension, encephalopathy and febrile neutropenia. In addition, prolonged cytopenias, hypogammaglobulinemia, and serious infections can occur. [18]


Tisagenlecleucel (Kymriah) is approved for treatment of R/R DLBCL in adult patients who have received 2 or more lines of systemic therapy. Indications include DLBCL not otherwise specified, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Approval was based on the single-arm, open-label, multicenter, phase 2 JULIET trial in adults with R/R DLBCL and DLBCL after transformation from follicular lymphoma. Eligible patients must have been treated with at least 2 prior lines of therapy, including an anthracycline and rituximab, or relapsed following stem cell transplantation. [20]

Study patients received a single infusion of tisagenlecleucel following completion of lymphodepleting chemotherapy. The overall response rate for the 68 evaluable patients was 50% (95% CI: 37.6, 62.4) with a complete response (CR) rate of 32% (95% CI: 21.5, 44.8). With a median follow-up time of 9.4 months, the duration of response (DOR) was longer in patients with a best overall response of CR, as compared with a best overall response of partial response (PR). In patients who achieved CR, the estimated median DOR was not reached (95% CI: 10.0 months, not estimable [NE]). The estimated median response duration in patients in PR was 3.4 months (95% CI: 1.0, NE). Common adverse reactions included cytokine release syndrome, hypogammaglobulinemia, infections, and encephalopathy. [21]

Lisocabtagene maraleucel

Lisocabtagene maraleucel (Breyanzi) is a CD19-directed CAR T-cell therapy for adults with R/R large B-cell lymphoma (LBCL) after two or more lines of systemic therapy, including DLBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. It is not indicated for primary CNS lymphoma.

Safety and efficacy were evaluated in TRANSCEND, an open-label, multicenter, single-arm trial. Patients (n=268) with R/R large B-cell non-Hodgkin lymphoma after at least 2 lines of therapy. Study patients received a single infusion of lisocabtagene maraleucel following completion of lymphodepleting chemotherapy. Of those patients, 54% achieved CR (95% CI: 47%-61%) and 19% achieved PR (95% CI:14%-26%). Median duration of response for all responders was 16.7 months (CR was not reached; PR: 1.4 months [95% CI: 1.1-2.2 months). Among all responders, 65% had remission for at least six months and 62% had remission lasting at least nine months. Most common adverse reactions were fatigue, cytokine release syndrome, musculoskeletal pain, nausea, headache, encephalopathy, infections (pathogen unspecified), decreased appetite, diarrhea, hypotension, tachycardia, dizziness, cough, constipation, abdominal pain, vomiting, and edema. [22]

Natural killer cell therapy

Unlike anti-CD19 CAR T-cell therapy, treatment with natural killer (NK) cells that have been modified to express an anti-CD19 has been shown to promote no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline. A phase 1/2 trial of HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood, in 11 patients with relapsed or refractory CD19-positive cancer, reported response to treatment in the majority of cases, without the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease. [23]

Monoclonal antibodies

Polatuzumab vedotin-piiq (Polivy) is an FDA-approved anti-CD79b antibody drug indicated for multiply relapsed or refractory DLBCL. A clinical trial has shown longer duration of remission when polatuzumab is added to bendamustine and rituximab. Common reported adverse effects include progressive multifocal leukoencephalopathy (PML), peripheral neuropathy, tumor lysis syndrome and fetal toxicity. [24, 25]

Other monoclonal antibodies undergoing phase 2 clinical trials include the following:

  • Brentuximab vedotin 
  • Blinatumomab 
  • Tafasitamab 

Mosunetuzumab is the newest monoclonal antibody; it binds to CD3 and CD20. A phase 1/2 clinical trial showed long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphoma (NHL) who had received at least 1 prior therapy, who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and for whom there was no available therapy that would be expected to improve survival. Compared with patients who had already progressed despite CAR T-cell therapy, patients treated with mosunetuzumab showed better response (objective response rate 37%,complete remission 22%). Common adverse reaction included cytokine release syndrome, headache, and insomnia. [26]

Hematopoietic cell transplantation 

Patients with relapsed or refractory DLBC should be considered for autologous hematopoietic cell transplantation (HCT) when CAR T-cell therapy is not available. For transplant-ineligible patients, the goal of care should be limiting the symptoms. CAR T-cell therapy can be administered. Such patients can participate in newer clinical trials. [16]



Complications arising from therapy include the following:



Radiation oncologists are often consulted because radiation plays a role in management of B-cell lymphoma; it is considered the treatment of choice in early-stage indolent lymphoma and has a role in consolidation of treatment in localized aggressive lymphoma.

A surgical consultation is indicated when central venous access devices are employed, especially when stem cell or bone marrow transplantation is considered.



Patients with lymphoma who are being managed at peripheral health care facilities may require their care to be transferred to a tertiary care or research institute for access to clinical trials and investigational agents.

Patients who are profoundly ill or are experiencing significant complications from either the disease or its therapy also warrant transfer to a facility that is better equipped to handle such emergencies.



Typically, no dietary restrictions exist for patients with non-Hodgkin lymphoma (NHL). Patients with prolonged neutropenia following chemotherapy, especially those undergoing high-dose chemotherapy with hematopoietic precursor cell rescue, are provided with a reduced-bacteria diet. Patients with high tumor burden undergoing chemotherapy may be at risk for tumor lysis syndrome and sometimes require a diet low in uric acid and potassium.