Anti-CD19 CAR T-Cell Therapy Shows ‘Clinically Significant’ Response Rates in Richter’s Transformation

Anti-CD19 chimeric-antigen receptor (CAR) T-cell therapy leads to clinically significant response rates and manageable safety in patients with Richter’s transformation, according to a retrospective multicenter study presented at the 66^th American Society of Hematology Annual Meeting & Exposition in San Diego, California.

Fifty-four patients (median age, 62.6 years) across the United States and Europe were treated with anti-CD19 CAR-T cells; 20 (37%) with tisagenlecleucel, four (7%) with axicabtagene ciloleucel, and one (2%) with lisocabtagene maraleucel. Forty-six (85%) patients received fludarabine with cyclophosphamide as lymphodepletion, while eight (15%) received bendamustine. Before lymphodepletion, 39 (72%) patients had an Eastern Cooperative Oncology Group (ECOG) score of 0-1, and 15 (28%) had an ECOG score of 2-3. The cohort had a median of two prior lines of treatment, including Bruton tyrosine kinase inhibitors in 67% of patients.

The overall response rate (ORR) was 65%, and the complete response (CR) rate was 46% at one month and 50% at three months postinfusion. At a median follow-up of 20.2 months, the median overall survival (OS) was 14.4 months (95% CI, 8.8-19.2). The six-month progression-free survival (PFS) was 56% (95% CI, 42%–70%), and the 12-month PFS was 41% (95% CI, 27%-56%). The median PFS was 24.6 months (95% CI, 16-32) for those who achieved CR or partial response, compared to 1.2 months (95% CI, 0.92-1.6) for those with stable or progressive disease.

Forty-seven (87%) patients experienced cytokine release syndrome (CRS) of any grade, while 10 (21%) experienced grades 3 or 4 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 12 (22%) patients, with five (42%) being high-grade. Twenty-two (41%) patients had an infection, most commonly bacterial (71%). Among the seven (13%) patients who proceeded to allogeneic hematopoietic stem cell transplant after CAR-T cell infusion, four (57%) died due to either transplant-related toxicities (75%) or progressive disease (25%).

High disease burden, determined by lactate dehydrogenase levels before CAR-T infusion (150 vs 274 mU/ml), was associated with a higher incidence of toxicity related to CAR-T. Mortality was “significantly associated” with the development of ICANS (P=.027), an ECOG performance status of 2-3 at the time of CAR-T infusion (P<.001), and no response at one month after CAR-T infusion (P=.001), according to an univariable analysis. Genetic aberrations such as deletion 17p, 13q, 11q, trisomy 12, TP53 mutations, or IGHV mutational status did not significantly affect response rates.

“These findings could potentially pave the way for new treatment paradigms in the management of this high-risk and challenging patient population,” the researchers concluded.

Reference

Beyar-Katz O, Benjamini O, Delgado J, et al. “CD19 CAR-T cell therapy is effective in richter transformation: a multicenter retrospective analysis by the European research initiative on chronic lymphocytic leukemia.” Abstract #4504. Presented at the 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.