Long-Term Outcomes of CAR T-Cell Therapy in Patients With CLL

Treatment with CD19-directed chimeric antigen receptor (CAR) T-cell therapy appeared to cure a “significant subset” of a large cohort of patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to data presented at the 66th American Society of Hematology Annual Meeting & Exposition by Benjamin F. Frost, of the Perelman School of Medicine at University of Pennsylvania in Philadelphia.

The analysis included 31 total patients from two separate studies. Of the patients, 14 patients received CD19-directed CAR T-cell monotherapy and 17 patients received CAR T-cell therapy with at least six months of ibrutinib during and after infusion.

The monotherapy cohort had a median follow-up after infusion of 9.1 years (range, 1.2-13.4), while the CAR T-cell with ibrutinib cohort had a median follow-up of 6.1 years (range, 1.4-7.3). The overall cohort had a median follow-up of 6.5 years (range, 1.2-13.4).

Can CLL Be Cured by CAR T-Cell Therapy?

Among patients who achieved one year of partial response or more after infusion, the five-year progression-free survival (PFS) rate was 57.1% (95% CI, 22.0-92.3) with monotherapy and 64.7% (95% CI, 37.2-92.2) with concurrent ibrutinib. The five-year overall survival (OS) rates with monotherapy and combination therapy were 78.6% (95% CI, 53.9-100) and 70.6% (95% CI, 44.8-96.4), respectively.

Overall, 24 patients (77.4%) who achieved one year without disease progression remained progression free at their last follow-up, including 19 patients who had follow-up longer than five years.

In the first year after infusion, 22 patients (71%) were in complete response (CR) while nine had less than a CR. The study found patients with a CR had significantly higher PFS (P=.014) and OS (P=.046) versus patients with less than a CR.

In the concurrent ibrutinib group, 11 of the 17 patients (64.7%) discontinued ibrutinib while in clinical remission, of which 10 (91%) remained in remission without further treatment. The median time to ibrutinib discontinuation was 1.2 years (range, 0.4-5.5) after CAR T-cell infusion.

“We report long-term follow-up on a large cohort of CLL patients treated with CD19-directed CAR T-cells,” Frost and colleagues summarized. “Despite the poor prognosis of these patients at time of treatment, these long-term follow-up data suggest a significant subset of patients have been cured of relapsed or refractory CLL with CD19-directed CAR T-cell therapy.”

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 & Exposition. December 7-10; San Diego, California.