Conditioning chemotherapy followed by chimeric antigen receptor (CAR) T-cell therapy may be acceptably tolerated by heavily pretreated patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphoma (B-NHL), according to results from a phase 1 trial published in JCI Insight.
The trial investigated the long-term safety and tolerability of therapy with CD19-targeted CAR T-cells that included a CD28 costimulatory domain with or without conditioning chemotherapy for patients with R/R CLL and indolent B-NHL.
The study included results from 20 patients: 16 patients had R/R CLL and 4 had R/R indolent B-NHL. Overall, 70% of patients were male, and patients had a median age of 63 years. Of the 20 patients, 17 received cyclophosphamide, bendamustine, or fludarabine- and cyclophosphamide-containing conditioning chemotherapy prior to CAR T-cell infusion, and 5 patients with CLL received ibrutinib during autologous T-cell collection or CAR T-cell infusion.
Ibrutinib therapy was found to modulate autologous T-cell phenotype. Ex vivo expansion of T-cells (median 143.3-fold vs 26.1-fold; P =.040), as well as proportions of CD4+ (median 58.4% vs 5.6%; P =.0061) and CD8+ CAR T-cells (median 29.0% vs 1.9%; P =.047) with a CD62L+CD127+ immunophenotype, were significantly greater in patients on ibrutinib at time of leukapheresis compared with ibrutinib-naive patients.
Of 12 evaluable patients with CLL receiving conditioning chemotherapy, 3 achieved complete response (CR); 2 of these patients were negative for measurable residual disease. At a median follow-up of 53 months, all patients who had achieved CR remained progression-free, and a subgroup of patients achieved durable CR.
All 20 patients experienced cytokine release syndrome, resulting in the second infusion being withheld in 6 of 11 patients receiving split-dose CAR T-cell infusions. However, few patients experienced grades 3 and 4 CRS (10%) or neurological events (10%).
1. Geyer MB, Rivière I, Sénéchal B, et al. Safety and tolerability of conditioning chemotherapy followed by CD19-targeted CAR T cells for relapsed/refractory CLL [published online April 2, 2019]. JCI Insight. doi:10.1172/jci.insight.122627