Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Department of Internal Medicine, Södersjukhuset, Stockholm, Sweden.
Eur J Haematol. 2023 Nov;111(5):715-721. doi: 10.1111/ejh.14065. Epub 2023 Jul 27.
We examined the efficacy and toxicity of the PI3Kδ inhibitor idelalisib in combination with rituximab salvage therapy in consecutively identified Swedish patients with chronic lymphocytic leukemia (CLL).
Thirty-seven patients with relapsed/refractory disease were included. The median number of prior lines of therapy was 3 (range 1-11); the median age was 69 years (range 50-89); 22% had Cumulative Illness Rating Scale (CIRS) >6 and 51% had del(17p)/TP53 mutation. The overall response rate was 65% (all but one was partial response [PR]). The median duration of therapy was 9.8 months (range 0.9-44.8). The median progression-free survival was 16.4 months (95% CI: 10.4-26.3) and median overall survival had not been reached (75% remained alive at 24 months of follow-up). The most common reason for cessation of therapy was colitis (n = 8, of which seven patients experienced grade ≥3 colitis). The most common serious adverse event was grade ≥3 infection, which occurred in 24 patients (65%).
Our real-world results suggest that idelalisib is an effective and relatively safe treatment for patients with advanced-stage CLL when no other therapies exist. Alternative dosing regimens and new PI3K inhibitors should be explored, particularly in patients who are double-refractory to inhibitors of BTK and Bcl-2.
我们研究了 PI3Kδ 抑制剂idelalisib 联合利妥昔单抗挽救疗法在连续确诊的瑞典慢性淋巴细胞白血病（CLL）患者中的疗效和毒性。
共纳入 37 例复发/难治性疾病患者。先前治疗线数中位数为 3 （范围 1-11）；中位年龄为 69 岁（范围 50-89）；22%的患者累积疾病评分量表（CIRS）>6，51%的患者存在 del(17p)/TP53 突变。总体缓解率为 65%（所有患者均为部分缓解[PR]）。中位治疗持续时间为 9.8 个月（范围 0.9-44.8）。中位无进展生存期为 16.4 个月（95%CI：10.4-26.3），中位总生存期尚未达到（75%的患者在 24 个月随访时仍存活）。停药的最常见原因是结肠炎（n=8，其中 7 例患者发生≥3 级结肠炎）。最常见的严重不良事件是≥3 级感染，发生在 24 例患者（65%）中。
我们的真实世界研究结果表明，idelalisib 是晚期 CLL 患者在无其他治疗方法时的一种有效且相对安全的治疗选择。应探索替代剂量方案和新的 PI3K 抑制剂，特别是在对 BTK 和 Bcl-2 抑制剂双重耐药的患者中。
