The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
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 www.clincialtrials.gov as #NCT02289222.
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“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]
Citations
Cites
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PD-1 blockade induces responses by inhibiting adaptive immune resistance
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Improved survival in multiple myeloma and the impact of novel therapies
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Immunologic Correlates of the Abscopal Effect in a Patient with Melanoma
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Self-citationMolecular and Biochemical Aspects of the PD-1 Checkpoint Pathway
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Pneumonitis in Patients Treated With Anti–Programmed Death-1/Programmed Death Ligand 1 Therapy
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Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma
Chari, A., Suvannasankha, A., Fay, J. W., Arnulf, B., Kaufman, J. L., Ifthikharuddin, J. J., Weiss, B. M., Krishnan, A. Y., Lentzsch, S., Comenzo, R. L., et al. (2017) · Blood · doi:10.1182/blood-2017-05-785246 · Cited by 444
Constantinidou, A., Alifieris, C., & Trafalis, D. T. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.09.008 · Cited by 342
Mateos, M., Blacklock, H. A., Schjesvold, F. H., Oriol, A., Simpson, D., George, A., Goldschmidt, H., Larocca, A., Chanan-Khan, A. A., Sherbenou, D. W., et al. (2019) · The Lancet Haematology · doi:10.1016/s2352-3026(19)30110-3 · Cited by 259
Usmani, S. Z., Schjesvold, F., Oriol, A., Karlin, L., Cavo, M., Rifkin, R. M., Yimer, H. A., LeBlanc, R., Takezako, N., McCroskey, R. D., et al. (2019) · The Lancet Haematology · doi:10.1016/s2352-3026(19)30109-7 · Cited by 251
Metadata
- 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
- 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
- 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 › Clinical Neurology › 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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