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ASCO 2022: Fixed-duration (FD) Ibrutinib (I) + Venetoclax (V) for First-Line (1L) Treatment (tx) of Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): Three-Year Follow-Up from the FD Cohort of the Phase 2 CAPTIVATE Study

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At the American Society of Clinical Oncology (ASCO) Annual Meeting in 2022, Dr. Bill Wierda of MDACC presented the follow-up three-year data of the fixed duration (FD) ibrutinib (I) + venetoclax (V) for first-line (1L) treatment (treatment) of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

CAPTIVATE is a large and vital multicenter phase 2 study of 1L I+V in CLL, and the two-year results were presented last year at ASCO 2021. Those results can be found here.

Results from ASCO 2022:

  • 159 patients were studied with a median age of 60 years old. They included patients with significant high-risk features including del(17p)/TP53 mutation (17%), unmutated IGHV (uIGHV; 56%), and complex karyotype (19%).
  • 147 (92%) and 149 (94%) patients completed treatment with I and V, respectively.
  • With one year of additional follow-up, the median time in the trial was 39 months.
  • The overall response rate (ORR) was 96%, the same in patients with high-risk features.
  • The number of complete responses (CR) in patients only increased slightly from 55% to 57% of all patients when going from two years to three.
  • Encouragingly, among patients achieving CR, 93% had durable responses lasting ≥12 months post-treatment.
  • Of patients with undetectable measurable (minimal) residual disease or uMRD in peripheral blood at 3-month post-treatment, 66/85 (78%) evaluable patients maintained uMRD through 12-mo post-treatment.
  • At 36 months, progression-free survival (PFS) was 88% (95% CI 82–92), and OS was 98% (95% CI 94–99). regardless of the presence of high-risk features.
  • All patients are off treatment; no new serious adverse events were noted in the third year.
  • As of January 2022, 12 patients were retreated with ibrutinib alone after their disease progressed (treatment duration range 3-29 months). Of those with data, 7/9 had partial responses, and 2/9 had stable disease.

Conclusions:

This trial offers more good news. Fixed duration I+V provides deep, durable responses and significant time without progression, including those with high-risk markers. I+V ticks all the boxes as a chemotherapy-free, all oral, once-a-day, fixed duration first-line therapy for almost anyone with CLL/SLL. The extra 12 months of follow-up provided no surprises. There were no new deaths or serious side effects in the third year. Though the numbers were small, it was also encouraging to see that retreatment with ibrutinib was largely effective in those whose disease had progressed.

The odds are good that I+V will soon be a welcomed approved frontline therapy in CLL/SLL in Europe and the USA based on this and the GLOW trial where I+V was compared to chlorambucil and obinutizumab.

That said, we still need to study whether taking two drugs together is the best approach or does sequencing therapies provide better overall survival. Those analyses are happening, but they will be slow to read out. And let’s also not forget that these two costly medications must be affordable for all who might benefit.

Watch my monologue on the abstract below:

Here is the link to the actual ASCO abstract: Fixed-duration (FD) ibrutinib (I) + venetoclax (V) for first-line (1L) treatment (tx) of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Three-year follow-up from the FD cohort of the phase 2 CAPTIVATE study.

Stay strong. We are all in this together.

Brian

Brian Koffman MDCM (retired) MS Ed (he, him, his)
Co-Founder, Executive VP, and Chief Medical Officer, CLL Society, Inc.

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