Characterization And Outcomes Of The Spanish Patients

Topic: Chronic lymphocytic leukemia and related disorders — Clinical

Background:The combination of fixed duration (FD) ibrutinib and venetoclax (I+V) was approved for patients withpreviously untreated chronic lymphocytic leukemia (CLL) based on two pivotal studies. However, there islimited data on the outcomes and management of I+V in Spanish CLL patients.

Aims:To describe the baseline characteristics, efficacy, and safety outcomes of previously untreated CLL patients whoreceived FD ibrutinib plus venetoclax (I+V) in GLOW or CAPTIVATE FD studies and were recruited in Spain.Methods:Post-hoc analysis of pooled data from Spanish CLL patients enrolled in the pivotal studies GLOW andCAPTIVATE FD cohort were performed to characterize and evaluate the outcomes for patients recruited in thesetrials in Spain. Only the patients that received fixed duration I+V were analyzed. Efficacy outcomes includedinvestigator assessed progression-free survival (PFS), overall survival (OS), time to next treatment (TTNT) wereevaluated with Kaplan-Meier methodology and overall response rate (ORR) was reported. Safety data was alsoassessed.

Results:Phase III RCT (Randomized Clinical Trial) GLOW and phase II clinical trial CAPTIVATE FD cohort included 10 and17 patients from Spain, respectively; therefore, the study size for this analysis is 27 patients. In this cohort,median age was 64 years old, 14.8% of patients had del(17p) and 70.4% of patients had unmutated IGHV, aslightly higher proportion of high-risk characteristics than in the main cohorts of the trials. With a medianfollow-up of 49.7 months, median PFS, OS and TTNT were not reached. The 4-year PFS, OS and TTNT estimateswere 80.0%, 96.0% and 83.6%, respectively. ORR was 96.3%, with 63.0% of patients achieving CR/CRi. Thesafety profile was consistent with previous findings for both Ibrutinib and venetoclax, with mostly manageableadverse events reported. Regarding TEAEs (Treatment Emergent Adverse Events) of interest, the most commonany grade adverse events were neutropenia (55.6%), diarrhea (40.7%) and thrombocytopenia (29.6%) with themost common grade 3–4 events being also neutropenia (48.1%), thrombocytopenia (14.8%) and diarrhea(7.4%). Hypertension of any grade was reported in 7 patients, however, only 1 patient experienced a grade ≥3event. No fatal events among all TEAE occurred, and no cases of atrial fibrillation, cardiac arrest, cardiac failure,sudden death nor ischemic stroke were reported.

Summary/Conclusion:Given the absence of real-world evidence of I+V, this analysis represents a relevant sample of the results forpatients treated with the fixed-duration combination of I+V in Spain in the context of a clinical trial. The resultsof this analysis suggest that I+V was efficacious and well tolerated in this cohort of patients from Spain withpreviously untreated CLL, findings consistent with the main cohorts of the GLOW and CAPTIVATE clinical trials.These results may contribute to the understanding of treatment outcomes and management specific to the CLLpopulation in Spain. The key limitation of this analysis is the low number of enrolled patients.

https://clin.larvol.com/abstract-detail/EHA 2024/70978920