A phase II trial demonstrated that fixed-duration ibrutinib (Ibr) plus venetoclax (Ven) provides durable progression-free survival (PFS) in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with effective retreatment options after disease progression. Researchers presented their findings at the Society of Hematologic Oncology 2024 Annual Meeting.
The CAPTIVATE study evaluated first-line treatment with Ibr and Ven in patients with CLL or SLL. The study focused on two cohorts: a measurable residual disease (MRD)-guided randomized discontinuation cohort (MRD cohort) and a fixed-duration (FD) cohort. The primary objective was to assess outcomes for patients with high-risk genomic features in the FD cohort and to evaluate retreatment outcomes in both the FD cohort and the placebo arm of the MRD cohort.
In the FD cohort, patients received three cycles of Ibr followed by 12 cycles of Ibr+Ven. After the end of treatment (EOT), patients with progressive disease (PD) could receive retreatment with Ibr or Ibr+Ven if PD occurred more than two years after EOT.
The study included 159 patients in the FD cohort, with a median follow-up of 61.2 months. The five-year PFS rate was 67%, and the overall survival rate was 96%. Patients with undetectable MRD three months after EOT had significantly higher five-year PFS rates—83% for those with undetectable MRD in peripheral blood and 84% in bone marrow—compared with 48% and 50% in those with detectable MRD. In high-risk subgroups, five-year PFS rates varied, with 41% for patients with del(17p)/mutated TP53, 57% for those with complex karyotype, 64% for patients with del(11q), and 68% for those with unmutated immunoglobulin heavy chain variable.
Of 202 patients who completed Ibr+Ven (159 in the FD cohort and 43 in the MRD cohort’s placebo arm), 63 experienced PD, and 32 initiated retreatment with Ibr (25 patients) or Ibr+Ven (seven patients). Among the 22 patients evaluable for Ibr retreatment, the overall response rate (ORR) was 86%, with one complete response (CR), 17 partial responses (PRs), one nodular PR, two cases of stable disease (SD), and one case of PD due to Richter transformation. In the seven evaluable patients for Ibr+Ven retreatment, the ORR was 71%, with one CR, four PRs, one PR with lymphocytosis, and one SD.
“With up to [five and a half] years of follow-up, FD Ibr+Ven continues to provide clinically meaningful PFS overall and in patients with high-risk genomic features,” the study concluded. “Ibr-based retreatment provides promising responses in patients needing subsequent therapy after the all-oral FD regimen of Ibr+Ven.”
Reference
Wierda WG, Jacobs R, Barr PM, et al. Outcomes in high-risk subgroups after fixed-duration ibrutinib (Ibr) + venetoclax (Ven) for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): up to 5.5 years of follow-up in the phase 2 CAPTIVATE study. Abstract #CLL-057. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.