Terpos Evangelos, Gavriatopoulou Maria, Ntanasis-Stathopoulos Ioannis, Malandrakis Panagiotis, Fotiou Despina, Migkou Magdalini, Theodorakakou Foteini, Spiliopoulou Vasiliki, Kostopoulos Ioannis V, Syrigou Rodanthi-Eleni, Eleutherakis-Papaiakovou Evangelos, Gkolfinopoulos Stavros, Tsitsilonis Ourania E, Kastritis Efstathios, Dimopoulos Meletios A
Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens.
Department of Biology, School of Science, National and Kapodistrian University of Athens, Athens.
Haematologica. 2024 Aug 1;109(8):2594-2605. doi: 10.3324/haematol.2023.284347.
Preclinical and clinical data demonstrate synergy between belantamab mafodotin (belamaf) and immunomodulatory drugs with limited overlapping toxicities. We investigated the safety and efficacy of belamaf with lenalidomide 25 mg on days 1-21 every 28 days and dexamethasone 40 mg weekly (belamaf-Rd) in transplant-ineligible patients with newly diagnosed multiple myeloma. Thirty-six patients (median age, 72.5 years) were randomized to receive belamaf at three different doses (2.5, 1.9, or 1.4 mg/kg) every 8 weeks. The dosing schedule was extended to every 12 weeks to mitigate ocular toxicity. Most common grade ≥3 adverse events were fatigue (n=21, 58.3%), rash (n=6, 16.7%), diarrhea (n=8, 22.2%) and COVID-19 (n=5, 13.9%). Grade 3-4 ocular adverse events, comprising visual acuity decline from baseline and/or keratopathy, were reported in 39/216 (18.1%), 33/244 (13.5%), and 26/207 (12.6%) ophthalmological assessments in the 2.5, 1.9, and 1.4 mg/kg cohorts, respectively. Importantly, grade 3-4 keratopathy was identified in 9/216 (4.2%), 1/244 (0.4%) and 1/207(0.5%) assessments. Most patients (32/36, 88.9%) were treated with the extended, every-12-week schedule, during which 40, 33 and 16 doses were withheld due to ocular adverse events in the 2.5, 1.9, and 1.4 mg/kg cohorts, respectively. Overall, the rates of very good partial response and better and complete response and better were 83.3% and 52.8%, respectively, without significant differences among cohorts. Over a median follow-up of 20.3 months no disease progression was reported; six patients discontinued treatment due to infection-related death (4 cases of COVID-19, 2 cases of pneumonia) and one patient withdrew consent. Based on the toxicity/efficacy balance, the recommended phase II dose was 1.9 mg/kg every 8 weeks, extended to every 12 weeks because of toxicity. In conclusion, Belamaf-Rd, with the extended schedule for belamaf, showed important clinical activity and a significant improvement of ocular adverse events with minimal impact on vision-related functioning in an elderly, non-transplant eligible population.
临床前和临床数据表明，贝兰他单抗马福多汀（belamaf）与免疫调节药物之间存在协同作用，且毒性重叠有限。我们研究了在每28天的第1 - 21天使用25 mg来那度胺和每周使用40 mg地塞米松（belamaf-Rd方案）的情况下，belamaf对新诊断的不适于移植的多发性骨髓瘤患者的安全性和疗效。36例患者（中位年龄72.5岁）被随机分配，每8周接受三种不同剂量（2.5、1.9或1.4 mg/kg）的belamaf治疗。给药方案延长至每12周以减轻眼部毒性。最常见的≥3级不良事件为疲劳（n = 21，58.3%）、皮疹（n = 6，16.7%）、腹泻（n = 8，22.2%）和新型冠状病毒肺炎（COVID-19，n = 5，13.9%）。在2.5、1.9和1.4 mg/kg队列中，分别有39/216（18.1%）、33/244（13.5%）和26/207（12.6%）的眼科评估报告了3 - 4级眼部不良事件，包括视力较基线下降和/或角膜病变。重要的是，在9/216（4.2%）、1/244（0.4%）和1/207（0.5%）的评估中发现了3 - 4级角膜病变。大多数患者（32/36，88.9%）接受了延长至每12周的给药方案，在此期间，2.5、1.9和1.4 mg/kg队列分别因眼部不良事件而有40、33和16剂药物未给药。总体而言，非常好的部分缓解及以上和完全缓解及以上的比例分别为83.3%和52.8%，各队列之间无显著差异。在中位随访20.3个月期间，未报告疾病进展；6例患者因感染相关死亡（新型冠状病毒肺炎4例，肺炎2例）停止治疗，1例患者撤回同意。基于毒性/疗效平衡，推荐的II期剂量为每8周1.9 mg/kg，因毒性原因延长至每12周。总之，采用延长的belamaf给药方案的Belamaf-Rd方案在老年、不适于移植的人群中显示出重要的临床活性，眼部不良事件有显著改善，对视力相关功能影响最小。
