Paolo Ghia, MD, PhD, Professor of Medical Oncology at the Università Vita-Salute San Raffaele in Milan, Italy, discusses data comparing ibrutinib plus venetoclax combination therapy with chlorambucil + obinutuzumab combination therapy in patients with chronic lymphocytic leukemia (CLL).
CLL is a rare cancer that affects the white blood cells, specifically B cells. In patients with CLL, the cancer mainly manifests in the bloodstream. Early signs and symptoms may include swollen lymph nodes, fatigue, weight loss, fever, night sweats and/or frequent infections. The underlying cause is thought to be a combination of genetic and other unknown factors.
Ibrutinib is a tyrosine kinase inhibitor and venetoclax is a B-cell lymphoma 2 protein inhibitor, both approved by the U.S. Food and Drug Administration (FDA) for the treatment of CLL. The combination ibrutinib plus venetoclax (Ibr+Ven) is an oral, once-daily, chemotherapy-free first-line treatment for CLL. The CAPTIVATE clinical trial (NCT02910583) was a phase 2, multicenter, 2-cohort study evaluating Ibr+Ven for the treatment of treatment-naïve patients with CLL. The GLOW clinical trial (NCT03462719) was a phase 3 randomized, open-label, study in patients with CLL treated with Ibr+Ven versus chlorambucil (Clb) + obinutuzumab (Obi).
Data on Ibr+Ven benefit across genomic subgroups in patients with CLL was recently presented at the 2025 American Society of Hematology (ASH) Annual Meeting.
Incidence of baseline genomic aberrations were similar in patients treated with Ibr+Ven in CAPTIVATE and GLOW. IGHV was unmutated (uIGHV) in 41.8% and 58.8% and mutated (mIGHV) in 56.3% and 31.8%. The most frequently mutated genes were SF3B1, PCLO, NOTCH1-ICD, ATM, IGLL5, and TP53.
Complete response rates were higher with Ibr+Ven versus Clb+Obi across all genomic subgroups in GLOW. In patients treated with Ibr+Ven in both CAPTIVATE and GLOW, complete response, overall response rate, and undetectable MRD (uMRD) rates 3 months after treatment across subgroups were generally similar to those observed in all patients treated with Ibr+Ven.
There were no statistically significant differences in progression-free survival between mutant versus wild-type subgroups, except for lower rates in patients with uIGHV versus mIGHV, and lower rates in patients with TP53 mutant versus wild-type. Additionally, there were no statistically significant differences in overall survival between mutant versus wild-type subgroups, except for IGHV and TP53.
At baseline, BCNX mutations were found in 13.9% of pts in the CAPTIVATE FD cohort and 13.4% of pts in the MRD cohort. There were no statistically significant differences in progression-free survival or overall survival between BCNX mutant versus wild-type subgroups in the FD cohort, but progression-free survival and overall survival were significantly longer in the BCNX wild-type versus mutant subgroup in the MRD cohort.
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To learn more about CLL and other rare hematologic conditions, visit https://checkrare.com/diseases/hematologic-disorders/