TY - JOUR
T1 - A pilot study of pembrolizumab in smoldering myeloma
T2 - Report of the clinical, immune, and genomic analysis
AU - Manasanch, Elisabet E.
AU - Han, Guangchun
AU - Mathur, Rohit
AU - Qing, Yun
AU - Zhang, Zheng
AU - Lee, Hans
AU - Weber, Donna M.
AU - Amini, Behrang
AU - Berkova, Zuzana
AU - Eterovic, Karina
AU - Zhang, Shaojun
AU - Zhang, Jianhua
AU - Song, Xingzhi
AU - Mao, Xizeng
AU - Morgan, Margaret
AU - Feng, Lei
AU - Baladandayuthapani, Veera
AU - Futreal, Andrew
AU - Wang, Linghua
AU - Neelapu, Sattva S.
AU - Orlowski, Robert Z.
N1 - Publisher Copyright:
© 2019 by The American Society of Hematology.
PY - 2019
Y1 - 2019
N2 - 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 1024 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-g 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. This trial was registered at www.clinicaltrials.gov as #NCT02603887.
AB - 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 1024 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-g 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. This trial was registered at www.clinicaltrials.gov as #NCT02603887.
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U2 - 10.1182/bloodadvances.2019000300
DO - 10.1182/bloodadvances.2019000300
M3 - Article
C2 - 31405950
AN - SCOPUS:85070769114
SN - 2473-9529
VL - 3
SP - 2400
EP - 2408
JO - Blood Advances
JF - Blood Advances
IS - 15
ER -