Year in Review: Diffuse Large B-Cell Lymphoma

Second-line treatment for diffuse large B-cell lymphoma (DLBCL) got a big boost in 2022 with new indications for a pair of chimeric antigen receptor (CAR) T-cell therapies, while an antibody-drug conjugate moved one step closer to shaking up treatment in the first-line setting.

CAR-T Products Move to Second-Line

In April, axicabtagene ciloleucel (axi-cel; Yescarta) became the first CAR T-cell therapy approved as initial treatment for relapsed or refractory large B-cell lymphoma. Then in June, the FDA approved lisocabtagene maraleucel (liso-cel; Breyanzi) for a similar group of patients.

The FDA’s thumbs up moved CAR T-cell therapy to the earliest approved line of treatment since the class reached the market a half-decade ago. Both approvals apply to patients with disease that has proven refractory to or has relapsed within 12 months of first-line chemoimmunotherapy.

Axi-cel’s approval was based on findings from the ZUMA-7 trial, in which nearly 70% of the 359 randomized patients had DLBCL. After 2 years of follow-up, those treated with axi-cel had a median event-free survival (EFS) of 8.3 months, which was significantly longer than the 2.0 months with standard care (chemotherapy and stem-cell transplantation for patients who responded). EFS rates at 2 years were 40.5% with axi-cel and 16.3% with standard care.

Liso-cel’s approval was based on findings from the TRANSFORM and PILOT studies, and here again a majority of patients in both trials had DLBCL.

In the phase III TRANSFORM study, which included 184 large B-cell lymphoma patients with primary refractory or early relapsed disease, median EFS was significantly prolonged with liso-cel — 10.1 months versus 2.3 months with standard therapy. EFS rates at 1 year were 45% and 24%, respectively.

Liso-cel also picked up an indication for treating relapsed large B-cell lymphoma patients who are ineligible for stem-cell transplantation, due to comorbidities or age, based on findings from the PILOT study. In the phase II trial of 61 patients, 80% responded to the CAR T-cell therapy, including complete responses in 54%.

Polatuzumab Vedotin Takes Another Step Toward First Line

In August, drugmaker Genentech announced that the FDA had accepted its supplemental biologics licence application for a polatuzumab vedotin (Polivy) indication as part of a first-line regimen for DLBCL.

Support for the proposed indication came from the phase III POLARIX trial. At a median 28.2 months follow-up, investigator-assessed progression-free survival (PFS) was significantly improved when vincristine in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone) was replaced by polatuzumab vedotin, a recently approved antibody-drug conjugate.

At 2 years, PFS rates were 76.7% with the so-called pola-R-CHP regimen versus 70.2% with standard R-CHOP (stratified HR 0.73, 95% CI 0.57-0.95, P=0.02), according to findings presented at last year’s American Society of Hematology meeting.

A cost-effectiveness analysis published earlier this year suggested pola-R-CHP would be cost effective with a 5-year PFS rate of at least 66.1%.

Allo-Transplant Promising After CAR T-Cell Failure

Durable remissions were seen with allogeneic stem-cell transplantation after CAR T-cell failure for patients with relapsed or refractory large B-cell lymphoma, data from a multicenter study showed.

Among 88 patients, median PFS and overall survival (OS) reached 10 and 21 months, respectively, according to findings presented by Joanna Zurko, MD, of the Medical College of Wisconsin in Milwaukee, at the Transplantation & Cellular Therapy Meetings.

Both outcomes compared favorably with historical results for post-CAR-T progression, which is associated with a median OS of less than 6 months from the time of progression.

The study results may help inform decisions related to one of the key challenges of CAR T-cell therapy for large B-cell lymphoma, said Zurko. Although the therapy produces response rates north of 80% in patients with relapsed or refractory disease, these responses are durable in only 30% to 40% of cases.

Senior editor Charles Bankhead and staff writer Mike Bassett contributed to this year in review.