Rosenberg Aaron S, Maverakis Emanual, Costello Caitlin, Brem Elizabeth A, Wieduwilt Matthew Joseph, Luxardi Guillaume, Kaesberg Paul, Abedi Keon, Herbert Samantha, Tuscano Joseph
Division of Malignant Hematology/Cellular Therapy and Transplantation, University of California Davis School of Medicine, Sacramento, CA.
Department of Dermatology, University of California Davis School of Medicine, Sacramento, CA.
Blood Neoplasia. 2025 Jan 16;2(3):100067. doi: 10.1016/j.bneo.2025.100067. eCollection 2025 Aug.
Clarithromycin is a macrolide antibiotic with anti-multiple myeloma (MM) activity when combined with dexamethasone and immunomodulatory agents. This phase 1/2 study of clarithromycin, ixazomib, pomalidomide, and dexamethasone (ClIPd) assessed tolerability and efficacy in relapsed/refractory MM. The primary end points were the maximal tolerated and recommended phase 2 dose. Key secondary end points were the overall response rate (ORR) (≥partial response), disease control rate (DCR) (≥stable disease), progression-free survival (PFS), and overall survival (OS). All 4 medications were given at full dose for 6 cycles. Pomalidomide, ixazomib, and dexamethasone were given at reduced doses with full-dose clarithromycin in subsequent maintenance cycles until unacceptable toxicity or progression. Clarithromycin was withheld during weeks 1 to 2 of cycle 1 to facilitate correlative studies. A total of 28 patients were evaluable for response/survival. The ORR was 75%; DCR was 100%; 56% achieved ≥very good partial response (VGPR), whereas 14% achieved complete response (CR)/stringent CR. High-risk cytogenetics were not associated with ORR (Fisher exact test, = 1) or ≥VGPR rates (Fisher exact test, = .42). The median PFS was 22.2 months (95% confidence interval [CI], 13.3 to not reached [NR]). There was no difference in the median PFS between patients with del(17p) (26.8 months; 95% CI, 10.2 to NR) and those without (22.2 months; 95% CI, 13.3 to NR; log rank, = .4). The median OS was NR. ClIPd combines convenient oral administration, a tolerable side effect profile, and long duration of disease control. This trial was registered at www.clinicaltrials.gov as #NCT02542657.
克拉霉素是一种大环内酯类抗生素，与地塞米松和免疫调节剂联合使用时具有抗多发性骨髓瘤（MM）的活性。这项关于克拉霉素、伊沙佐米、泊马度胺和地塞米松（ClIPd）的1/2期研究评估了复发/难治性MM患者的耐受性和疗效。主要终点是最大耐受剂量和推荐的2期剂量。关键次要终点是总缓解率（ORR）（≥部分缓解）、疾病控制率（DCR）（≥病情稳定）、无进展生存期（PFS）和总生存期（OS）。所有4种药物均全剂量给药6个周期。在随后的维持周期中，泊马度胺、伊沙佐米和地塞米松减量给药，克拉霉素全剂量给药，直至出现不可接受的毒性或疾病进展。在第1周期的第1至2周停用克拉霉素，以方便进行相关性研究。共有28例患者可评估缓解/生存情况。ORR为75%；DCR为100%；56%达到≥非常好的部分缓解（VGPR），而14%达到完全缓解（CR）/严格CR。高危细胞遗传学与ORR（Fisher精确检验，P = 1）或≥VGPR率（Fisher精确检验，P = 0.42）无关。中位PFS为22.2个月（95%置信区间[CI]，13.3至未达到[NR]）。伴有del(17p)的患者（26.8个月；95%CI，10.2至NR）和不伴有del(17p)的患者（22.2个月；95%CI，13.3至NR；对数秩检验，P = 0.4）的中位PFS无差异。中位OS未达到。ClIPd具有口服给药方便、副作用可耐受和疾病控制时间长的特点。本试验在www.clinicaltrials.gov上注册，注册号为#NCT02542657。
