This content was current as of the date it was released. In science and medicine, information is constantly changing and may become out-of-date as new data emerge.
The CAPTIVATE study data has been highly anticipated. At ASH 2020, we got important results. Dr. Wierda presented the results of Minimal (Measurable) Residual Disease (MRD) cohort using MRD status to guide therapy: Undetectable MRD (uMRD) was achieved in >2/3 of patients with 12 cycles of I+V, and the 30 months progression free survival or PFS rates was an impressive ≥95%.
For more on the design of the CAPTIVATE trial and the results of the MRD cohort, here is my interview with Dr. Wierda soon after ASH 2020. For a patient’s perspective, catch Mark Hoffman’s discussion of his positive experience in the trial.
Now at ASCO (American Society of Clinical Oncology) 2021 Annual meeting, held virtually, Dr. Paolo Ghia reports the results of the fixed duration or FD arm.
Pts aged ≤70 yrs. with treatment naive CLL/SLL, received 3 cycles of I followed by 12 cycles of I+V. The ibrutinib lead in was to reduce tumor burden and thus the risk of tumor lysis syndrome too that comes when too much cancer is killed too fast.
- 159 pts were enrolled whose median age was 60.
- High-risk features included del(17p) or TP53 mutation in 17%; del(11q) in 18%; complex karyotype in 19%; and unmutated IGHV in 56%.
- Most patients were able to complete the planned treatment with 147 (92%) and 149 (94%) pts completing I and V, respectively.
- Median time on study was 27.9 months.
- With fixed-duration I+V, CR rate was 55% in the overall population and was consistent across high-risk subgroups.
- Of the 88 pts who achieved CR, 78 (89%) had durable CR (duration ≥1 y); 1 died 7 months after CR, and 9 with <1 y follow-up were not evaluable.
- ORR was 96%.
- uMRD response was achieved in 77% of patients in peripheral blood (PB) and 60% of pts in bone marrow (BM).
- 24-mo PFS was 95%; 24-mo OS was 98%.
- The purpose for the three month I lead in was to reduce the tumor burden and thus the risk of tumor lysis syndrome (TLS) when too much cancer is killed too quickly, overwhelming the kidney’s ability to detoxify the blood. Of 34 pts with high baseline TLS risk based on tumor burden, 32 (94%) shifted to medium or low risk after I lead-in; no TLS occurred.
- Adverse events (AEs) or side effects were primarily mild. The most common serious common AEs were neutropenia (dangerously low neutrophil counts) in one third, hypertension in 6%, and milder neutrophil count decreased in 5%. AEs led to discontinuation of I in 4% and V in 2%.
First line I+V is an oral, once-daily, chemotherapy-free, fixed-duration treatment option that provides deep, durable responses in CLL patients, including those with high-risk features such as del(17p). PFS at 2 years of 95% seems similar to the uMRD arm at 30 months of ≥95%. While it is clearly simpler to have a FD therapy and the two-year results presented at ASCO are encouraging, longer term data are needed to determine if uMRD guided therapy will improve OS over FD. Another bigger unanswered question is if sequential drug use or using complementary combinations upfront, is the best choice. More research is coming, but one thing we know for sure is that I+V is a potent therapy, even for high-risk patients.
Here is the link to the ASCO 2021 abstract.
Stay strong. We are all in this together.
Brian Koffman MDCM (retired) MS Ed
Co-Founder, Executive VP and Chief Medical Officer
CLL Society, Inc.