Current treatment regimens with oral agents ibrutinib (Ibr) and venetoclax (Ven) in various combinations and durations are being studied to find the optimum benefit with tolerable side effects or adverse events (AE). Because these two oral targeted drugs work in very different or orthogonal ways, there is good reason to expect excellent results. The ideal would be to reach undetectable minimal residual disease (uMRD) is explained in this Bloodline. In addition, fixed duration combined therapies such as Ibr plus Ven during the current Covid 19 pandemic would offer the advantage of avoiding the immune suppression caused by the CD20 inhibitor, obinutuzumab, which is currently used in combination with Ven as a dual agent fixed duration treatment.
At the annual meeting of the American Society of Hematology (ASH) 2021, Dr. Mathew Davids from the Dana-Farber Cancer Institute in Boston interviews Dr. Bill Wierda from the MD Anderson Cancer Center in Houston. They discuss the 2-year results of the Captivate Study evaluating outcomes in previously untreated CLL patients receiving oral therapy with Ibr and Ven therapy in CLL patients.
- There were 164 patients averaging 58 years old with no prior treatment evaluated in the study. Many had various high-risk markers. All patients first received 3 cycles of Ibr followed by 12 cycles of Ibr plus Ven.
- Eighty-six of the 149 or 58% of the randomized patients reached uMRD after the scheduled 15 months of therapy.
- At the start of cycle 16, those 86 with uMRD were randomized into two groups, including 43 patients who received continued therapy with Ibr and 43 who received placebo.
- Of those who reached MRD (as opposed to uMRD) by the start of cycle 16, 32 patients received additional treatment with Ibr plus Ven, while 32 received Ibr plus placebo.
- After 24 months in the post-16th cycle, those who achieved uMRD had similar excellent responses to subsequent treatment with Ibr as with placebo. The estimated 36-month progression-free survival (PFS) was 100%. The hope is that treatment can be discontinued if uMRD is achieved within the initial 15 cycles.
- At 24 months after the initial 15 cycles, those who had achieved only MRD received either continued Ibr plus Ven or Ibr with placebo. Those receiving the Ibr plus Ven were more likely to achieve uMRD in blood and bone marrow than those treated with Ibr plus placebo. However, the estimated PFS at three years was 97% in both groups Ibr plus placebo and Ibr plus Ven.
- Patient side effects (AE) of the more severe or higher type 3 included neutropenia or decreased neutrophils in 36%, hypertension or high blood pressure in 10%, decreased platelets in 5%, and diarrhea in 5% of patients.
Conclusions: In previously untreated patients with CLL, there is great hope for a durable treatment-free remission following fixed duration combination therapy with Ibr plus Ven. At three years, none of the patients who achieved uMRD at 15 months had progressed.
For those who do not achieve uMRD with the initial 15 rounds of combined therapy, continued treatment with Ibr combined with Ven provides the best hope for better uMRD.
The hope is that with this type of tailored therapy using uMRD as a surrogate marker telling us when it is wise to stop therapy, we can give patients their best duration and combination of therapy to safely stop treatment and achieve a significant disease-free period off the drugs.
Please enjoy this interview with Dr. Wierda from the virtual ASH meeting held in December 2021.
Be strong. We are all in this together.
Dr. Michael R. Green, MD and CLL patient