Isatuximab monotherapy in relapsed/refractory multiple myeloma: A Japanese, multicenter, phase 1/2, safety and efficacy study.
Kazutaka SunamiKenshi SuzukiMasaki RiMorio MatsumotoChihiro ShimazakiHideki AsaokuHirohiko ShibayamaKenichi IshizawaHiroyuki TakamatsuTakashi IkedaDai MaruyamaHitomi KanekoMichihiro UchiyamaToru KiguchiSatoshi IyamaHirokazu MurakamiKeishiro TakahashiKeisuke TadaSandrine MacéHélène Guillemin-PaveauShinsuke IidaPublished in: Cancer science (2020)
Isatuximab, an anti-CD38 monoclonal antibody, targets cells that strongly express CD38 including malignant plasma cells. This open-label, single-arm, multicenter, phase 1/2 trial investigated the tolerability/safety and efficacy of isatuximab monotherapy in Japanese patients with heavily pretreated, relapsed/refractory multiple myeloma (RRMM). In Phase 1, patients were sequentially assigned to receive isatuximab once weekly (QW) in cycle 1 (4 weeks) and every 2 weeks (Q2W) in subsequent cycles. Cohort 1 (n = 3) received 10 mg/kg QW/Q2W; cohort 2 (n = 5) received 20 mg/kg QW/Q2W. No dose-limiting toxicities occurred; the recommended dose for the single-arm phase 2 study (n = 28) was 20 mg/kg QW/Q2W. The overall safety profile was consistent with the current knowledge of isatuximab. The most common adverse events were infusion reactions (42.9%; 12/28); all were grade 1/2 and generally occurred during the first infusion. The overall response rate with 20 mg/kg QW/Q2W isatuximab was 36.4% (12/33); patients with high-risk cytogenetic abnormalities had comparable results. In phase 2, the median progression-free survival was 4.7 (95% confidence interval, 3.75 to not reached) months. Median overall survival was not reached. Isatuximab monotherapy was well tolerated and effective in patients with heavily pretreated RRMM including high-risk cytogenetic patients. This trial is registered at ClinicalTrials.gov as NCT02812706.
Keyphrases
- open label
- multiple myeloma
- end stage renal disease
- free survival
- induced apoptosis
- phase ii
- clinical trial
- ejection fraction
- phase iii
- newly diagnosed
- chronic kidney disease
- monoclonal antibody
- acute myeloid leukemia
- low dose
- acute lymphoblastic leukemia
- peritoneal dialysis
- combination therapy
- prognostic factors
- healthcare
- cell cycle arrest
- cell death
- phase ii study
- radiation therapy
- squamous cell carcinoma
- high resolution
- patient reported