Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma Journal Article

Authors: Badros, A.; Hyjek, E.; Ma, N.; Lesokhin, A.; Dogan, A.; Rapoport, A. P.; Kocoglu, M.; Lederer, E.; Philip, S.; Milliron, T.; Dell, C.; Goloubeva, O.; Singh, Z.
Article Title: Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma
Abstract: Programmed death 1 (PD-1) receptor and its ligand (PD-L1) facilitate immune evasion in multiple myeloma (MM). We hypothesized that pembrolizumab, PD-1-antibody, can enhance antimyeloma cellular immunity generated by pomalidomide, leading to improved clinical responses. In this single-center, phase 2 study, 48 patients with relapsed/refractory MM (RRMM) received 28-day cycles of pembrolizumab, 200 mg IV every 2 weeks, pomalidomide 4 mg daily for 21 days, and dexamethasone 40 mg weekly. Patients had a median of 3 (range: 2-5) lines of therapy, median age 64 (range: 35-83) years, and had received both an immune modulatory drug (IMiD) and proteasome inhibitor: (35 [73%] of 48) were refractory to both; (31 [70%]) had received an autologous transplant, and (30 [62%]) had high-risk cytogenetics. Adverse events grade 3 to 4 occurred in (19 [40%] of 48 patients), including hematologic toxicities (19 [40%]), hyperglycemia (12 [25%]), and pneumonia (7 [15%]). Autoimmune events included pneumonitis (6 [13%]) and hypothyroidism (5 [10%]), mostly £ grade 2. Objective responses occurred in (29 [60%] of 48) patients, including stringent complete response/complete response (4 [8%]), very good partial response (9 [19%]), and partial response (16 [33%]); median duration of response was 14.7 months. At median follow-up of 15.6 months, progression-free survival (PFS) was 17.4 months and overall survival was not reached. Analyses of pretreatment marrow samples revealed a trend for increased expression of PD-L1 in responding patients and longer PFS with increased T-lymphocyte infiltrates, irrespective of PD-1 expression. Pembrolizumab, pomalidomide, and low-dose dexamethasone have acceptable safety and durable responses in RRMM patients. This trial was registered at as #NCT02289222. © 2017 by The American Society of Hematology.
Journal Title: Blood
Volume: 130
Issue: 10
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2017-09-07
Start Page: 1189
End Page: 1197
Language: English
DOI: 10.1182/blood-2017-03-775122
PROVIDER: scopus
PUBMED: 28461396
Notes: Article -- Export Date: 2 October 2017 -- Source: Scopus
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MSK Authors
  1. Alexander Meyer Lesokhin
    106 Lesokhin
  2. Ahmet Dogan
    162 Dogan