The PI3Kδ inhibitor zandelisib on intermittent dosing in relapsed/refractory follicular lymphoma: Results from a global phase 2 study

IF 7.6 2区 医学 Q1 HEMATOLOGY HemaSphere Pub Date : 2024-08-06 DOI:10.1002/hem3.138
Andrew D. Zelenetz, Wojciech Jurczak, Vincent Ribrag, Kim Linton, Graham P. Collins, Javier L. Jiménez, Mark Bishton, Bhagirathbhai Dholaria, Andrea Mengarelli, Tycel J. Phillips, Nagendraprasad Sungala, Gerardo Musuraca, Oonagh Sheehy, Eric Van Den Neste, Mitsuhiko Odera, Lu Miao, Daniel P. Gold, Richard G. Ghalie, Pier L. Zinzani
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Abstract

In this global phase 2 study in patients with relapsed/refractory follicular lymphoma (FL), zandelisib was administered on intermittent dosing to mitigate immune-related adverse events and infections that have been reported with oral PI3Kδ inhibitors administered daily continuously. Eligible patients with measurable disease and progression after at least two prior therapies were administered zandelisib until disease progression or intolerability. The primary efficacy endpoint was objective response rate (ORR) and the key secondary efficacy endpoint was duration of response (DOR). We report on 121 patients with FL administered zandelisib on intermittent dosing after 8 weeks of daily dosing for tumor debulking. The median number of prior therapies was 3 (range, 2–8) and 45% of patients had refractory disease. The ORR was 73% (95% confidence interval [CI], 63.9–80.4), the complete response (CR) rate was 38% (95% CI, 29.3–47.3), and the median DOR was 16.4 months (95% CI, 9.5–not reached). With a median follow-up of 14.3 months (range, 1–30.5), the median progression-free survival was 11.6 months (95% CI, 8.3–not reached). Twenty-one patients (17%) discontinued therapy due to an adverse event. Grade 3–4 class-related toxicities included 6% diarrhea, 5% lung infections, 3% colitis (confirmed by biopsy or imaging), 3% rash, 2% AST elevation, and 1% non-infectious pneumonitis. Zandelisib achieved a high rate of durable responses in heavily pretreated patients with relapsed/refractory FL. The intermittent dosing resulted in a relatively low incidence of severe class-related toxicities, which supports the evaluation of zandelisib as a single agent and in combination with indolent B-cell malignancies.

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PI3Kδ抑制剂zandelisib在复发/难治性滤泡性淋巴瘤中的间歇用药:一项全球性2期研究的结果。
在这项针对复发性/难治性滤泡性淋巴瘤(FL)患者的全球性二期研究中,赞德利西布采用间歇给药的方式,以减轻口服PI3Kδ抑制剂每日连续给药时出现的免疫相关不良事件和感染。符合条件的患者如果患有可测量的疾病,且在之前接受过至少两种疗法后病情出现进展,将接受赞德利西布治疗,直至病情恶化或无法耐受。主要疗效终点是客观反应率(ORR),关键的次要疗效终点是反应持续时间(DOR)。我们报告了121例FL患者的治疗情况,这些患者在经过8周的肿瘤剥脱每日给药后,采用间歇给药的方式服用赞德利西布。既往治疗次数的中位数为 3 次(范围为 2-8 次),45% 的患者患有难治性疾病。ORR为73%(95%置信区间[CI],63.9-80.4),完全应答(CR)率为38%(95% CI,29.3-47.3),中位DOR为16.4个月(95% CI,9.5-未达到)。中位随访时间为 14.3 个月(1-30.5 个月),中位无进展生存期为 11.6 个月(95% CI,8.3-未达到)。21名患者(17%)因不良事件中断治疗。3-4级相关毒性包括:6%腹泻、5%肺部感染、3%结肠炎(活检或影像学确诊)、3%皮疹、2%AST升高和1%非感染性肺炎。Zandelisib在重度预处理的复发/难治FL患者中取得了较高的持久应答率。间歇性给药导致严重类相关毒性的发生率相对较低,这为评估Zandelisib作为单药或与不活跃B细胞恶性肿瘤联合用药提供了支持。
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来源期刊
HemaSphere
HemaSphere Medicine-Hematology
CiteScore
6.10
自引率
4.50%
发文量
2776
审稿时长
7 weeks
期刊介绍: HemaSphere, as a publication, is dedicated to disseminating the outcomes of profoundly pertinent basic, translational, and clinical research endeavors within the field of hematology. The journal actively seeks robust studies that unveil novel discoveries with significant ramifications for hematology. In addition to original research, HemaSphere features review articles and guideline articles that furnish lucid synopses and discussions of emerging developments, along with recommendations for patient care. Positioned as the foremost resource in hematology, HemaSphere augments its offerings with specialized sections like HemaTopics and HemaPolicy. These segments engender insightful dialogues covering a spectrum of hematology-related topics, including digestible summaries of pivotal articles, updates on new therapies, deliberations on European policy matters, and other noteworthy news items within the field. Steering the course of HemaSphere are Editor in Chief Jan Cools and Deputy Editor in Chief Claire Harrison, alongside the guidance of an esteemed Editorial Board comprising international luminaries in both research and clinical realms, each representing diverse areas of hematologic expertise.
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