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Cited by 197Multiple Myeloma Research and TreatmentsCancer Immunotherapy and BiomarkersMultiple Sclerosis Research Studies

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

Badros, Ashraf, Hyjek, Elizabeth, Ma, Ning, Lesokhin, Alexander, Dogan, Ahmet, Rapoport, Aaron P., Kocoglu, Mehmet, Lederer, Emily +5 more·2017·Blood
DOI 10.1182/blood-2017-03-775122
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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 www.clincialtrials.gov as #NCT02289222.

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Crossref · 10.1182/blood-2017-03-775122

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  • Combining pembrolizumab with lenalidomide or pomalidomide and dexamethasone showed efficacy in single-arm trials but was associated with severe hematological and infectious toxicities and immune-related adverse events that led to termination of some clinical trials.

    “Although single-agent activity was limited, combining pembrolizumab with lenalidomide or pomalidomide and dexamethasone showed efficacy in single-arm trials. However, these combinations were associated with severe hematological and infectious toxicities, as well as immune-related adverse events such as pneumonia, hypothyroidism, adrenal insufficiency, hepatitis, and vitiligo. These adverse events”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [180]

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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.
Affiliations
  • University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (US)
  • University of Chicago (US)
  • Memorial Sloan Kettering Cancer Center (US)
  • Memorial Sloan Kettering Cancer Center, New York, NY
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2017-09-07
Volume
130
Issue
10
Pages
1189-1197
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2017-03-775122
OpenAlex
W2610269487
Cited by
197
References
38
Citations by year
2026: 4 · 2025: 8 · 2024: 10 · 2023: 10 · 2022: 12 · 2021: 24 · 2020: 31 · 2019: 34 · 2018: 46 · 2017: 16 · 2016: 1
FWCI
26.76
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords
pembrolizumab, pomalidomide, low-dose dexamethasone, relapsed/refractory multiple myeloma, PD-1 inhibitors, PD-L1 expression, immune evasion, combination immunotherapy, T cell infiltration, progression-free survival, adverse events, pneumonitis, hypothyroidism, hematologic toxicity, hyperglycemia
MeSH terms
Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Demography, Dexamethasone, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Multiple Myeloma, Pneumonia, Thalidomide, Biomarkers, Tumor, Treatment Outcome, Kaplan-Meier Estimate, Intention to Treat Analysis, Antibodies, Monoclonal, Humanized

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