Patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy who achieved a complete response (CR) after a year went on to have good long-term overall survival (OS) and progression-free survival (PFS), according to findings that were presented at the 66th American Society of Hematology Annual Meeting and Exposition.
The data suggest, researchers say, that despite the difficulty of treating these patients, some do go on to achieve something resembling a cure.
Trials have found that CAR-T therapy has produced durable responses in some patients with R/R CLL, but the data have been limited for longer-term outcomes. In this analysis, researchers assessed how patients fared after enrollment in two CAR-T trials.
Thirty-eight of the patients had R/R CLL with at least two prior treatments and then received anti-CD19 CAR-T treatment. Another 19 patients, in a different trial, had R/R CLL with at least one prior treatment and at least six months of ibrutinib treatment, which was continued during and after the CAR-T treatment. An analysis was performed on the 31 patients who had achieved at least a partial response (PR) without progression after a year.
Patients were an average of 62 years old at infusion and had received a median of three prior therapy lines, and 90.3% had an adverse cytologic or molecular marker. The median follow-up was 9.1 years for those treated with CAR-T alone, 6.1 years for those treated with concurrent ibrutinib, and 6.5 years across all patients.
At five years after their infusions, the PFS for those who achieved one year of PR or better was 57.1% after CAR-T alone (95% CI 22.0-92.3) and 64.7% with concurrent ibrutinib (95% CI 37.2-92.2). The OS for these patients five years after infusion was 78.6% after CAR-T alone (95% CI 53.9-100) and 70.6% with concurrent ibrutinib (95% CI 44.8-96.4).
“There were no relapses among patients who achieved four years of PFS,” said study author Bejamin Frost, MD, a clinical fellow in medicine at Brigham and Women’s Hospital in Boston, who presented the findings. “Thus, CAR-T responses are durable and possibly curative for patients with R/R CLL.”
Of these 31 patients, 71% achieved a CR, and 29% had less than a CR in the first year after their infusions. Both the OS and the PFS were higher for patients with a CR than those with less than a CR (p=0.014 and 0.046, respectively).
“This suggests that even among patients who have a prolonged response to CAR-T therapy, achieving a CR is prognostically important,” Dr. Frost said.
Hypogammaglobulinemia was common, with 90.3% of patients receiving IVIG at least once and 67.7% still requiring IVIG at their last follow-up, researchers reported.
Dr. Frost was asked by an audience member whether the persistence of the CAR-T transgene should simply be considered continued therapy, and therefore the word “cure” might be a stretch; after all, those on ibrutinib with no detectable measurable residual disease after 10 years aren’t considered cured because they’re still on treatment.
Dr. Frost said some patients on trial had persistence of the CAR-T transgene but also recovery of B-cell counts, suggesting that maybe there is some escape of the B cells, so they don’t have recurrence of their CLL.
“Maybe,” he said, “in those patients we could say ‘cure.’”
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Frost BF, Frey N, Hexner EO, et al. Curing CLL: long-term outcomes of chronic lymphocytic leukemia patients with at least one year of response to CART-19 therapy. Abstract 588. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 8, 2024; San Diego, California.
