Anti-CD19 CAR-T cells trigger durable remissions of CLL, B-cell lymphoma
Anti-CD19 CAR-T cells led to highly durable remissions in chronic lymphocytic leukemia and B-cell lymphoma, according to data from the longest follow-up study of patients who received this treatment presented at ASCO20 Virtual Scientific Program.
“Chimeric antigen receptors targeting CD19 have been shown in multicenter trials to cause complete remissions,” Kathryn Cappell, MD, PhD, fellow of Medical Oncology Service at National Cancer Institute/National Institutes of Health, said in the presentation. “The complete remission rate with the approved anti-CD19 CAR T cell products is 40% to 54%. However, the long-term durability of these responses is unclear.”
To examine the long-term durability of remissions and long-term adverse effects after anti-CD19 CAR T-cell therapy, Cappell and colleagues evaluated 43 patients with anti-CD19 CAR T cells preceded by conditioning chemotherapy of cyclophosphamide plus fludarabine between 2009 and 2015. Patients were grouped into three cohorts for treatment, which differed in the CAR T-cell production process and conditioning chemotherapy dose.
Of the 43 patients, 65% had diffuse large B-cell lymphoma or primary mediastinal B cell lymphoma; 19% had low-grade lymphoma; 16% had chronic lymphocytic leukemia; 49% had chemotherapy-refractory lymphoma and 19% had received autologous transplant as their last treatment before enrollment, according to the presentation.
The ORR was 76%, 58% of the treatments had a best response or complete response and 23% had a best response or partial response, Cappell said in her presentation. Of the 25 patients who achieved CR, 60% were evaluable and ongoing at the last follow-up appointment, with their duration of response ranging from 43 to 113 months.
The researchers found that median event-free survival was 55 months and the median OS was not reached, but there was no observed difference in event-free survival or OS based on lymphoma type or cohort.
Cappell also reported that patients who achieved a complete response had higher peak CAR levels compared with patients who did not, and those who reached a duration of response of greater than 3 years also had higher peak CAR levels. Further, long-term adverse effects were rare, excluding B-cell depletion and hypogammaglobulinemia; however, these both improved over time, according to the abstract.
“Overall, the very durable responses seen in our study raise the possibility, but do not prove, that anti-CD19 CAR T cells may be curative for some types of B-cell lymphoma,” Cappell concluded in her presentation.
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Cappell K, et al. Abstract 3012. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.