Patients with aggressive B-cell lymphomas (BCL) whose disease relapses after chimeric antigen receptor (CAR) T-cell therapy experience poor outcomes, particularly among patients who relapse within 30 days, according to the results of study published in the journal Blood.

“Treatment of patients with relapsed/refractory aggressive BCL after failure of anti-CD-19 CAR T-cell constitutes an unmet medical need, and further innovative strategies are needed,” the authors wrote in their report.

In this study, data of 550 patients from the DESCAR-T registry were evaluated for outcomes after receiving anti-CD19-CAR T-cell therapy with either axicabtagene ciloleucel or tisagenlecleucel. The median follow-up was 7.9 months.


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The majority of patients in the cohort had diffuse large B-cell lymphoma, 57% of patients had more than 3 lines of prior treatment, and 19% had a prior autologous transplant. There were 39% of patients with a lactate dehydrogenase (LDH) prior to infusion above the upper normal limit (UNL).

There were 58% of patients who achieved a complete remission, 11% who experienced a partial remission, and 1% with stable disease. There were 43.3% who had progressive disease. The overall progression-free survival (PFS) for the entire cohort was 4.6 months and median overall survival (OS) was 11.1 months.

The median time to CAR T-cell failure was 2.7 months, with the majority of patients developing relapse at 2 months or later. There were 22.7% of patients who experienced progression within 30 days, 42.9% between days 31 and 90, and 34.5% after day 90. The median PFS after failure was 2.8 months and the median OS was 5.2 months. For patients whose disease relapsed within 30 days of CAR T-cell therapy, the median PFS and OS were 1.7 months and 1.9 months, respectively.

There were data available for 154 patients who were treated after CAR T-cell therapy, which most commonly included lenalidomide and targeted therapy, with bispecific antibodies, radiotherapy, and combined immunochemotherapy to a lesser extent.

Response to subsequent treatment was low, with an overall rate of 14.1% and a complete remission rate of 6.6%. There were 70.8% of patients whose disease progressed.

Shorter OS after CAR T-cell failure was associated with several factors in a multivariate analysis, including a LDH level greater than the UNL prior to infusion (hazard ratio [HR], 2.10; 95% CI, 1.16-3.78; P =.0136), C-reactive protein level higher than the UNL prior to infusion (HR, 1.11; 95% CI, 1.04-1.19; P =.0027), and progression or relapse within 30 days (HR, 2.93; 95% CI, 1.56-5.50; P =.0009). Treatment with lenalidomide after failure was associated with longer OS (HR, 0.42; 95% CI, 0.21-0.82; P =.0116).

The authors concluded that “this DESCAR-T registry study confirms that outcomes of patients following failure of CAR T-cell treatment remain extremely poor, and outcome are worse in the event of failure within the first month.”

Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.

Reference

Di Blasi R, Le Gouill S, Bachy E, et al. Outcomes of patients with aggressive B-cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T analysis. Blood. 2022;140:2584-2593. doi: 10.1182/blood.2022016945