免疫失调是慢性淋巴细胞白血病（CLL）的一个标志。抗 CD20 抗体（例如利妥昔单抗 [R]）可与维奈托克 (Ven) 联合治疗 CLL。然而，抗CD20抗体会增加低丙种球蛋白血症的风险，而Ven对免疫失调的影响仍不确定。我们在 MURANO 试验 (NCT02005471) 中报告了接受 VenR 和苯达莫司汀 R (BR) 治疗的复发/难治性 CLL 患者的长期免疫变化。患者被随机分配接受固定期限 VenR（2 年 Ven；前 6 个月 VenR）或 BR（6 个月）。在联合治疗 (EOCT) 结束、治疗结束（EOT；仅 VenR 组）以及 EOCT 后 12 个月和 24 个月时评估免疫细胞水平。总体而言，130/194 名 VenR 治疗患者和 134/195 名 BR 治疗患者完成治疗，且疾病未进展。在完成 VenR 联合治疗的患者中，中位免疫球蛋白 (Ig)G 和 IgM 水平从基线降低至 EOT（分别为 p≤≤0.01 和 p≤≤0.0001）；到 24 个月时，EOT 后 IgG 已恢复至基线水平，IgM 较基线有所增加 (p≤≤0.001)。中位 IgA 水平从基线增加至 12 (p ≤ 0.0001) 和 EOT 后 24 个月 (p ≤ 0.0001)。在接受 BR 治疗的患者中，在评估的时间点内 IgG、IgA 和 IgM 水平的变化并不显着，并且到 24 个月时，EOCT 后 IgG、IgA 和 IgM 高于基线水平。治疗时≥3级感染率较低。总体而言，VenR 和 BR 观察到免疫恢复，治疗后 Ig 水平稳定。治疗后感染率普遍较低，这使得这些治疗 CLL 的方法非常容易耐受。© 2024 作者。约翰·威利 (John Wiley) 出版的 HemaSphere

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.© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.