What follows is our patient-friendly summary of this research.
Remissions remained durable in both treatment-naive (TN) and relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) patients treated with a fixed duration of obinutuzumab, ibrutinib, and venetoclax, but the triplet does lead to low blood counts in most patients,
Who Performed the Research and Where Was it Presented:
At the American Society of Clinical Oncology (ASCO) Annual Meeting in 2022, Dr. Kerry Rogers of OSU presented the results of the four-year follow-up from a phase 2 study of obinutuzumab, ibrutinib, and venetoclax in CLL.
Targeted therapies have revolutionized the management of CLL, but the best sequencing or combinations of therapies is not yet defined. This study looks at a potent triple combination for a fixed period of time.
Methods and Participants:
Initially, 25 TN and 25 R/R patients with CLL were enrolled. A later cohort added another 25 TN CLL patients. The average age was 58, 64% were men, and 8% had del(17p).
Treatment was given for over a year (14 cycles of 28-day each).
For those who were followed for 48 months, the estimated progression-free survival (PFS) and overall survival (OS) for the TN RR cohorts were 96%, and in the R/R cohort, they were 85% and 100%, respectively. Unfortunately, there was a death of a R/R at 51 months.
The most frequent adverse events were low neutrophils seen in 95%, with 73% having a severe drop. Similar but fewer severe decreases in counts were seen in the total white blood cells, lymphocytes, and platelets. Hypertension was seen in 85% and was more severe in 39%. Atrial fibrillation occurred in 11% of patients.
Conclusions and Comments:
This is a powerful combination with impressively durable responses in both TN and R/R patients.
The price of these strong responses is the high levels of low blood counts, a special concern during the pandemic. However, it is reassuring that infection was not listed as a common adverse event.
The unanswered question is whether these triplet results are better than that doublet of ibrutinib and venetoclax (I+V) already studied in the CAPTIVATE and GLOW trials. Also, does adding the obinutuzumab improve outcomes, or is it just making patients more immunosuppressed? More follow-up and research are needed to give the answers.
Links and Resources:
Watch my monologue on the abstract below:
Here is the ASCO publication: Four-year Follow-Up From a Phase 2 Study of Obinutuzumab, Ibrutinib, and Venetoclax in CLL.
Here is an interview with Dr. Rogers with more up-to-date data from VJ Onc.
Stay strong. We are all in this together.
Brian Koffman MDCM (retired) MS Ed (he, him, his)
Co-Founder, Executive VP, and Chief Medical Officer, CLL Society, Inc.