Fixed-Duration Regimen Substantially Benefits PFS in Patients With CLL/SLL

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Researchers at the 2024 ASCO Annual Meeting presented long-term survival outcomes of patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) who were treated with ibrutinib (Ibr) plus venetoclax (Ven).

The phase 2 CAPTIVATE study assessed the efficacy of the first-line combination of these agents in two cohorts: minimal residual disease (MRD)-guided randomized discontinuation and fixed duration. William G. Wierda, MD, PhD, and colleagues focused on outcomes in patients with high-risk genomic features from the fixed duration cohort. They also presented retreatment results for the fixed duration cohort and MRD cohort placebo arm.

Patients aged 70 or younger with untreated CLL/SLL received three cycles of Ibr, followed by 12 cycles of Ibr+Ven, regardless of genomic risk factors. Retreatment options included single-agent Ibr or Ibr+Ven for patients who experienced disease progression more than two years post-treatment.

In the fixed duration cohort (n=159), with a median follow-up of 61.2 months (range, 0.8-66.3), the 5-year progression-free survival (PFS) and overall survival (OS) rates were 67% and 96%, respectively (95% CI).

At 3 months post-treatment, patients had higher 5-year PFS rates with undetectable MRD in peripheral blood and bone marrow (83% and 84%) compared with those who had detectable MRD (48% and 50%).

Five-year PFS rates (95% CI) among patients with high-risk genomic features were:
• del(17p)/mutated TP53: 41%;
• complex karyotype: 57%;
• del(11q): 64%; and
• unmutated IGHV: 68%.

The researchers noted 18 secondary malignancies in 13 patients, with ten events occurring during fixed duration Ibr+Ven treatment, six after treatment, and two during retreatment. Of the 202 patients who received Ibr+Ven (fixed duration cohort n=159; MRD cohort placebo arm n=43), 63 experienced disease progression, with 68% of these cases occurring more than two years post-treatment. Thirty-two patients reinitiated treatment, with 25 receiving Ibr and seven receiving Ibr+Ven.

The median treatment duration for patients who were retreated with Ibr was 21.9 months (range, 0.03-50.4), and the overall response rate (ORR) was 86% among 22 evaluable patients. The best responses included one complete response, one nodular partial response, 17 partial responses, two stable diseases, and one progression (Richter transformation).

For patients who were retreated with Ibr+Ven, the median duration was 13.8 months (range, 3.7-15.1), with an ORR of 71% among seven evaluable patients, including one complete response, four partial responses, one partial response with lymphocytosis, and one stable disease.

The researchers concluded that the fixed-duration Ibr+Ven regimen provided substantial long-term PFS benefits in patients with high-risk genomic features and the broader population of patients with CLL/SLL. Dr. Wierda and colleagues added, “Ibr-based retreatment provides promising responses in patients needing subsequent therapy after the all-oral fixed duration regimen of Ibr+Ven.”

Pharmacyclics LLC funded the study.