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VTD-melphalan is well tolerated and results in very high rates of stringent CR and MRD-negative status in multiple myeloma

Authors Nadiminti K, Singh Abbi KK, Mott SL, Dozeman L, Tricot A, Schultz A, Behrends S, Zhan F, Tricot G

Received 10 May 2016

Accepted for publication 10 August 2016

Published 6 January 2017 Volume 2017:10 Pages 217—226

DOI https://doi.org/10.2147/OTT.S112423

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Jia Fan

Peer reviewer comments 2

Editor who approved publication: Dr Yao Dai

Kalyan Nadiminti,1,2 Kamal Kant Singh Abbi,2,3 Sarah L Mott,2 Lindsay Dozeman,2 Annick Tricot,2 Allyson Schultz,2 Sonya Behrends,2,3 Fenghuang Zhan,2,3 Guido Tricot2,3

1Division of Hematology/Oncology, 2Holden Comprehensive Cancer Center, 3Department of Internal Medicine, Blood and Marrow Transplantation, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Abstract: The addition of cytotoxic drugs to high-dose melphalan as a preparative regimen for autologous stem cell transplantation in multiple myeloma has not resulted in superior activity. Although novel agents have significantly improved outcome in multiple myeloma, their role in preparative regimens remains largely unknown. We have evaluated the toxicity and efficacy of combining bortezomib, thalidomide, and dexamethasone with high-dose melphalan. An institutional review board-approved retrospective analysis was performed on 100 consecutive patients receiving 153 transplants; 53 had tandem transplants; 64 patients received early transplants; and 36 had salvage transplantation. Endpoints were treatment-related toxicity and mortality, and quality of response post-transplantation with assessment of stringent complete remission (sCR) and minimal residual disease (MRD) status. Median age was 61 years, and median follow-up was 16.2 months. At 6 months, sCR was attained in 56% of patients and CR in 20%. An MRD status, assessed by sensitive (10-4) multiparameter flow cytometry, was achieved in 85%. The 100-day mortality rate was 2.6% (4/153); 1.8% for early transplants and 4.5% for salvage transplants. Grade 3–5 non-hematologic toxicities were mainly related to metabolism/nutrition; gastrointestinal and infectious problems. Median time to absolute neutrophil count of >500/µL was 12 days for both early and salvage transplantations. No significant differences in quality of response were observed between early and salvage transplantation or between single and tandem autologous stem cell transplantation. Since both sCR and MRD are excellent early surrogate markers for progression-free and overall survival, this regimen will likely be superior to melphalan alone, but it needs to be formally assessed in a randomized study.

Keywords: multiple myeloma, autologous transplantation, response, toxicity, mortality, minimal residual disease
 

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