Authored by Brian Koffman, MDCM (retired), MSEd
Bottom Line:
Ibrutinib+Venetoclax is approved in 78 countries from trials, but real world (RW) data are limited. This prospective CLL study reports safety and efficacy.
Who Performed the Research and Where Was it Presented:
Dr. Catherine Thieblemont from Saint Louis Hospital, Paris, France and colleagues including CLL Society’s Dr. Brian Koffman presented the results at the American Society for Hematology (ASH) Annual Meeting in 2025.
Background and Methods:
Ibrutinib+Venetoclax (I+V) is an all-oral fixed duration frontline therapy for chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL /SLL). More than five years of follow-up has shown significant progression-free (PFS) and overall survival (OS) benefits in clinical trials, but there is a need to see if the combination performs as well outside of trials in the community where results may not be as strong. This article pools data from two RW large prospective trials, REALITY-WW (international) and REALITY-2 (in Germany) to understand the “usage, factors for therapy decision, clinical response, and safety of FD Ibr+Ven in routine clinical practice.”
Results:
- Median time on study was 6.4 (0.1-19.0) months.
- Median age was 65 and 62.8% were male.
- TP53 mutations were seen in 7.4% of patients; 52.8% had an unmutated IGHV status.
- Overall response rate (ORR) was assessed in the 44 patients with ≥ 1 post-baseline assessment in REALITY-WW. Of these, 39 showed a response by the end of 6 cycles and 5 had stable disease.
- ORR at 6 months was 88.6% including complete responses (CR) in 29.5%.
- Among 129 treated patients, adverse events were reported in 61.2%; diarrhea was the most common at 14%. The most common serious adverse event was myocardial infarction (heart attack) in 1.6%.
- The dose was reduced in 13.2% (I) and 2.3% (V) of patients, respectively.
- There were no serious adverse events from tumor lysis syndrome (TLS) and no hospitalizations due to TLS.
- The most common factors associated with prescribers’ decision to initiate FD I+V were it being all-oral (91.3%), overall health status (87.3%), anticipated superior efficacy (84.1%), and general risk factors such as high tumor burden/genetic risk factors (81.0%).
Conclusions:
Frontline fixed-duration ibrutinib plus venetoclax in CLL achieves ORR of 81–97%, CR rates of 43–74%, and uMRD rates (<10⁻⁴) of 52–82% across clinical trials. At first that seems much better than achieved in the RW data where only 3 in 10 achieved a CR at 6 months, but those trials were all at least a year and responses deepen over time. And with the ORR similar (88.6% in the RW), it’s reasonable that the other measures of efficacy and safety could also be similar in and out of trials. That would be reassuring. Time will tell. Other all-oral combinations are now approved or in trials, offering CLL / SLL patients more options for care.
Links and Resources:
You can learn more details and read the actual abstract @ Real-world (RW) use of fixed-duration (FD) ibrutinib+venetoclax (Ibr+Ven) in patients (patients) with previously untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL / SLL): Pooled analysis of REALITY-worldwide (WW) and REALITY-2 prospective cohort studies.
