Extended Follow-up Shows Sustained Benefits of Acalabrutinib-Based Therapy in CLL

Acalabrutinib with or without obinutuzumab had sustained safety and efficacy in patients with treatment-naïve chronic lymphocytic leukemia (CLL), including those with high-risk genetic features, over six years of follow-up in the ELEVATE-TN study.

Progression-free survival (PFS) was significantly longer with acalabrutinib plus obinutuzumab versus acalabrutinib monotherapy, and median overall survival (OS) was significantly longer with acalabrutinib plus obinutuzumab compared with obinutuzumab plus chlorambucil.

The data were presented by Jeff Sharman, MD, of Willamette Valley Cancer Institute and Research Center/US Oncology Research in Eugene, Oregon, at the 65th American Society of Hematology Annual Meeting & Exposition.

The study included 535 patients with CLL, of which 179 received acalabrutinib monotherapy, 179 received acalabrutinib plus obinutuzumab, and 177 received obinutuzumab plus chlorambucil. The cohort had a median age of 70 years, 63% had unmutated immunoglobulin heavy chain variable region, and 14% had del(17p), mutated TP53, or both.

Data Update Verifies Superiority of Acalabrutinib in CLL Treatment

At the data cutoff of March 3, 2023, the median follow-up was 74.5 months (range, 0-89). Median PFS was 27.8 months with obinutuzumab plus chlorambucil, and was not reached with acalabrutinib plus obinutuzumab (hazard ratio [HR], 0.14; P<.0001) or acalabrutinib alone (HR, 0.23; P<.0001). Acalabrutinib with obinutuzumab was superior to monotherapy (HR, 0.58; P=.0229).

The estimated PFS rates at 72 months were 78% with acalabrutinib plus obinutuzumab, 62% with acalabrutinib, and 17% with obinutuzumab plus chlorambucil, and respective estimated rates of 72-month OS were 68%, 72%, and 53%. Median OS was not reached in either the acalabrutinib combination or monotherapy groups versus 74.9 months in the obinutuzumab plus chlorambucil group.

Overall, acalabrutinib appeared to maintain safety and efficacy outcomes previously reported after 58.2 months in ELEVATE-TN patients with treatment-naïve CLL.

Related: Jennifer Woyach, MD, Highlights Novel CLL Therapies Presented at ASH 2023

Reference

Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib ± obinutuzumab vs obinutuzumab + chlorambucil in treatment-naive chronic lymphocytic leukemia: six-year follow-up of Elevate-TN. Abstract #636. Presented at the 65th American Society of Hematology Annual Meeting and Exposition; December 9-12, 2023; San Diego, California.