Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma

作者：Chari, Ajai^*; Suvannasankha, Attaya; Fay, Joseph W.; Arnulf, Bertrand; Kaufman, Jonathan L.; Ifthikharuddin, Jainulabdeen J.; Weiss, Brendan M.; Krishnan, Amrita; Lentzsch, Suzanne; Comenzo, Raymond; Wang, Jianping; Nottage, Kerri; Chiu, Christopher; Khokhar, Nushmia Z.; Ahmadi, Tahamtan; Lonial, Sagar

来源：Blood, 2017, 130(8): 974-981.

DOI：10.1182/blood-2017-05-785246

• MONOTHERAPY
• LENALIDOMIDE
• COMBINATION
• BORTEZOMIB
• SURVIVAL
• CRITERIA
• CELLS
• CD38

Daratumumab plus pomalidomide and dexamethasone (pom-dex) was evaluated in patients with relapsed/refractory multiple myeloma with >= 2 prior lines of therapy who were refractory to their last treatment. Patients received daratumumab 16 mg/kg at the recommended dosing schedule, pomalidomide 4 mg daily for 21 days of each 28-day cycle, and dexamethasone 40 mg weekly. Safety was the primary end point. Overall response rate (ORR) and minimal residual disease (MRD) by next-generation sequencing were secondary end points. Patients (N = 103) received a median (range) of 4 (1-13) prior therapies; 76% received >= 3 prior therapies. The safety profile of daratumumab plus pomdex was similar to that of pom-dex alone, with the exception of daratumumab-specific infusion-related reactions (50%) and a higher incidence of neutropenia, although without an increase in infection rate. Common grade >= 3 adverse events were neutropenia (78%), anemia (28%), and leukopenia (24%). ORR was 60% and was generally consistent across subgroups (58% in double-refractory patients). Amongpatients with a complete response or better, 29% were MRD negative at a threshold of 10(-5). Among the 62 responders, median duration of response was not estimable (NE; 95% confidence interval [CI], 13.6-NE). At a median follow-up of 13.1 months, the median progression-free survival was 8.8 (95% CI, 4.6-15.4) months andmedian overall survival was 17.5 (95% CI, 13.3-NE) months. The estimated 12-month survival ratewas 66% (95% CI, 55.6-74.8). Aside from increased neutropenia, the safety profile of daratumumab plus pom-dex was consistent with that of the individual therapies. Deep, durable responses were observed in heavily treated patients. The study was registered at www.clinicaltrials.gov as # NCT01998971.

• 出版日期2017-8-24