Tags

Type your tag names separated by a space and hit enter

A pilot study of pembrolizumab in smoldering myeloma: report of the clinical, immune, and genomic analysis.
Blood Adv 2019; 3(15):2400-2408BA

Abstract

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-γ 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.

Authors+Show Affiliations

Department of Lymphoma/Myeloma.Department of Genomic Medicine.Department of Lymphoma/Myeloma.Department of Biostatistics.Department of Lymphoma/Myeloma.Department of Lymphoma/Myeloma.Department of Lymphoma/Myeloma.Department of Diagnostic Radiology, Division of Diagnostic Imaging.Department of Lymphoma/Myeloma.Genomics Platform, and.Department of Genomic Medicine.Department of Genomic Medicine.Department of Genomic Medicine.Department of Genomic Medicine.Genomics Platform, and.Department of Biostatistics.Department of Biostatistics.Department of Genomic Medicine.Department of Genomic Medicine.Department of Lymphoma/Myeloma.Department of Lymphoma/Myeloma. Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31405950

Citation

Manasanch, Elisabet E., et al. "A Pilot Study of Pembrolizumab in Smoldering Myeloma: Report of the Clinical, Immune, and Genomic Analysis." Blood Advances, vol. 3, no. 15, 2019, pp. 2400-2408.
Manasanch EE, Han G, Mathur R, et al. A pilot study of pembrolizumab in smoldering myeloma: report of the clinical, immune, and genomic analysis. Blood Adv. 2019;3(15):2400-2408.
Manasanch, E. E., Han, G., Mathur, R., Qing, Y., Zhang, Z., Lee, H., ... Orlowski, R. Z. (2019). A pilot study of pembrolizumab in smoldering myeloma: report of the clinical, immune, and genomic analysis. Blood Advances, 3(15), pp. 2400-2408. doi:10.1182/bloodadvances.2019000300.
Manasanch EE, et al. A Pilot Study of Pembrolizumab in Smoldering Myeloma: Report of the Clinical, Immune, and Genomic Analysis. Blood Adv. 2019 Aug 13;3(15):2400-2408. PubMed PMID: 31405950.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A pilot study of pembrolizumab in smoldering myeloma: 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, PY - 2019/04/15/received PY - 2019/07/01/accepted PY - 2019/8/14/entrez PY - 2019/8/14/pubmed PY - 2019/8/14/medline SP - 2400 EP - 2408 JF - Blood advances JO - Blood Adv VL - 3 IS - 15 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 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-γ 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. SN - 2473-9537 UR - https://www.unboundmedicine.com/medline/citation/31405950/A_pilot_study_of_pembrolizumab_in_smoldering_myeloma:_report_of_the_clinical,_immune,_and_genomic_analysis L2 - http://www.bloodadvances.org/cgi/pmidlookup?view=long&pmid=31405950 DB - PRIME DP - Unbound Medicine ER -