Journal
BLOOD ADVANCES
Volume 3, Issue 15, Pages 2400-2408Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/bloodadvances.2019000300
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Funding
- Anderson Cancer Center Support Grant (National Institutes of Health, National Cancer Institute) [P30 CA016672]
- Leukemia and Lymphoma Society Specialized Center of Research (LLS SCOR)
- Dr Miriam and Sheldon G. Adelson Medical Research Foundation
- Multiple Myeloma Research Foundation
- University of Texas Anderson Moon Shot Program
- The trial collaborator (Merck)
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Multiple myeloma is, in most patients, an incurable cancer. Its precursors can be identified with routine tests setting the stage for early intervention to prevent active myeloma. We investigated the efficacy and safety of pembrolizumab, an antiprogrammed cell death 1 antibody, in smoldering myeloma patients with intermediate/high risk of progression to symptomatic myeloma. Thirteen patients were treated with a median number of 8 cycles. One patient achieved a stringent complete response with bone marrow next-generation sequencing negativity at 10(-4) that is ongoing at 27 months (8%); 11 had stable disease (85%), and 1 progressed (8%). Three patients discontinued therapy due to immune-related adverse events: 2 with transaminitis and 1 due to tubulointerstitial nephritis. Immune profiling of bone marrow samples at baseline showed markers associated with a preexisting immune response in the responder compared with nonresponders and features of increased T-cell exhaustion in nonresponders. Consistent with this, transcriptome sequencing of bone marrow samples at baseline revealed an increased interferon-gamma signature in the responder compared with the nonresponders. In summary, our results suggest that smoldering myeloma may be immunogenic in a subset of patients, and therapies that enhance antitumor T-cell responses may be effective in preventing its progression.
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