Long-term immune changes in patients with relapsed/refractory chronic lymphocytic leukemia following treatment with venetoclax plus rituximab.

Immune dysregulation is a hallmark of chronic lymphocytic leukemia (CLL). Anti-CD20 antibodies (e.g., rituximab [R]) can be combined with venetoclax (Ven) to treat CLL. However, anti-CD20 antibodies can increase hypogammaglobulinemia risk, while the effects of Ven on immune dysregulation are still uncertain. We report long-term immune changes in VenR- and bendamustine-R (BR)-treated patients with relapsed/refractory CLL in the MURANO trial (NCT02005471). Patients were randomized to fixed-duration VenR (2 years Ven; VenR for the first 6 months) or BR (6 months). Immune cell levels were evaluated at the end of combination treatment (EOCT), end of treatment (EOT; VenR arm only), and 12 and 24 months post-EOCT. Overall, 130/194 VenR- and 134/195 BR-treated patients completed treatment without progressive disease. In patients who completed VenR combination therapy, median immunoglobulin (Ig)G and IgM levels decreased from baseline to EOT ( p  ≤ 0.01 and p  ≤ 0.0001, respectively); by 24 months, post-EOT IgG had returned to baseline level and IgM had increased from baseline ( p  ≤ 0.001). Median IgA levels increased from baseline to 12 ( p  ≤ 0.0001) and 24 months post-EOT ( p  ≤ 0.0001). In BR-treated patients, changes in IgG, IgA, and IgM levels across the assessed time points were not significant, and by 24 months, post-EOCT IgG, IgA, and IgM were above baseline levels. Grade ≥3 infection rates on treatment were low. Overall, immune recovery was observed with VenR and BR, with stabilization of Ig levels after treatment. Post-treatment infection rates were generally low, making these very tolerable therapies for CLL.
Competing Interests: Arnon P. Kater: AbbVie, AstraZeneca, BMS, Janssen, Roche/Genentech—research funding; Janssen, LAVA—patents & royalties pending; AstraZeneca, BMS, Roche/Genentech, Janssen, AbbVie, LAVA—membership on an entity's board of directors or advisory committees; AbbVie, AstraZeneca, Janssen—speakers fee. Barbara F. Eichhorst: Janssen, AbbVie, Lilly, AstraZeneca, BeiGene, MSD, Roche—consultancy; Janssen, AbbVie, BeiGene, AstraZeneca, Gilead, Lilly—research funding; Janssen, Roche, AbbVie, BeiGene, AstraZeneca—speakers bureau; Beigene—travel support. Carolyn J. Owen: AbbVie, Novartis, Janssen, AstraZeneca, Merck, Roche, Gilead, Incyte, Beigene—Honoraria. Ulrich Jaeger: Roche—consultancy, honoraria, and research funding; AbbVie, Beigene, AstraZeneca, Novartis, Miltenyi Biomedicine—membership on an entity's board of directors or advisory committees. Gilead, Sanofi—Honoraria. Brenda Chyla: AbbVie—current employment and holder of stock options in a privately held company. Michelle Boyer: Roche—current employment, stock ownership, and honoraria. Marcus Lefebure: Roche—current employment and equity holder in a publicly traded company and divested equity in a private or publicly traded company in the past 24 months. Rosemary Millen: Roche—current employment. Yanwen Jiang: Roche/Genentech—current employment; Roche—current equity holder in a publicly traded company. Maria Thadani‐Mulero: Roche Products Ltd.—current employment; Roche Group—current equity holder in a publicly traded company. John F. Seymour: Celgene, Roche, TG Therapeutics—consultancy.
(© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)