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Patients with CLL Lack Known Resistance Mechanisms After Disease Progression

By Patrick Daly Last Updated: November 28, 2023

Patients with chronic lymphocytic leukemia (CLL) who experienced disease progression after fixed-duration ibrutinib plus venetoclax did not exhibit mutations in BTK, PLCG2, and BCL2 associated with treatment resistance, suggesting that ibrutinib with or without venetoclax could be effective for retreatment, according to a pooled analysis of phase II trial patients.

“First-line fixed-duration combination treatment with ibrutinib plus venetoclax may mitigate development of resistance mechanisms associated with continuous single-agent targeted therapies,” wrote first author, Nitin Jain, MD, of the University of Texas MD Anderson Cancer Center in Houston, in Clinical Cancer Research.

Dr. Jain and colleagues reviewed 191 patients with CLL with or without progressive disease after completing the phase II CAPTIVATE study. The study intervention was three cycles of ibrutinib followed by 12 or 13 cycles of ibrutinib plus venetoclax.

Researchers reviewed risk factors present at baseline including del(11q), del(13q), del(17p), trisomy 12, complex karyotype, unmutated IGHV, and mutations in TP53, ATM, BIRC3, BRAF, CHD2, EZH2, FBXW7, MYD88, NOTCH1, POT1, RPS15, SF3B1, and XPO1. Additionally, variations and mutations associated with treatment resistance in BTK, PLCG2, and BCL2 were assessed at disease progression.

Over a median follow-up of 38.9 months, 29 out of 191 (15%) patients developed progressive disease. No baseline risk factors or mutations were significantly correlated with disease progression, and no BTK, PLCG2, or BCL2 mutations associated with treatment resistance were present at time of progression in 25 patients with available samples.

Among the 29 patients with progression, 16 were retreated with ibrutinib monotherapy and three with ibrutinib plus venetoclax. Of the 19 retreated patients, 17 achieved a partial response or better, one achieved stable disease, and one was pending evaluation.


Jain N, Croner LJ, Allan JN, et al. Absence of BTK, BCL2, and PLCG2 mutations in chronic lymphocytic leukemia relapsing after first-line treatment with fixed-duration ibrutinib plus venetoclax. Clin Cancer Res. 2023; doi:10.1158/1078-0432.CCR-22-3934

Original Source: Patients with CLL Lack Known Resistance Mechanisms After Disease Progression | Blood Cancers Today

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