Modified Hyper-CVAD With Proteasome Inhibition for Multiple Myeloma: A Single-Center Retrospective Analysis.


Journal

Clinical lymphoma, myeloma & leukemia
ISSN: 2152-2669
Titre abrégé: Clin Lymphoma Myeloma Leuk
Pays: United States
ID NLM: 101525386

Informations de publication

Date de publication:
12 2020
Historique:
received: 17 06 2020
revised: 20 07 2020
accepted: 26 07 2020
pubmed: 26 8 2020
medline: 20 11 2021
entrez: 26 8 2020
Statut: ppublish

Résumé

Although novel agents have changed the treatment landscape of multiple myeloma (MM), cytotoxic chemotherapy regimens continue to have a role in aggressive or rapidly progressive disease. In such cases, our institution has utilized a hyperfractionated cyclophosphamide regimen (termed mCAD), similar to hyper-CVAD, in which vincristine is omitted or replaced with a proteasome inhibitor (PI), either bortezomib or carfilzomib. On occasion, doxorubicin is also omitted because of patient history and provider preference. We retrospectively reviewed the charts of adult patients with MM receiving mCAD regimens at our institution between 2012 and 2016 and analyzed utilization patterns, toxicity profiles, and clinical outcomes. A total of 131 patients received mCAD, including 9% for newly diagnosed MM (NDMM), 18% attempting to optimize response to frontline therapy (OPT-MM), and 73% for treatment of relapsed/refractory MM (RRMM). Renal dysfunction was common; 31% had estimated glomerular filtration rate < 50 mL/min and 14% were dialysis dependent. The overall response rate was 83%, 63%, and 67% with a median progression-free survival of 17.4, 23.7, and 4.2 months, respectively, for NDMM, OPT-MM, and RRMM. Median overall survival was not reached for NDMM or OPT-MM, and was 15.2 months for RRMM. Most patients (90%) bridged to subsequent therapy, including 32% who proceeded to autologous transplantation. Hematologic, infectious, and cardiac toxicities were common and were similar to those expected for cytotoxic chemotherapy. mCAD regimens were safe and active across patient groups, including patients with renal dysfunction. Most patients were able to bridge to subsequent therapy.

Sections du résumé

BACKGROUND
Although novel agents have changed the treatment landscape of multiple myeloma (MM), cytotoxic chemotherapy regimens continue to have a role in aggressive or rapidly progressive disease. In such cases, our institution has utilized a hyperfractionated cyclophosphamide regimen (termed mCAD), similar to hyper-CVAD, in which vincristine is omitted or replaced with a proteasome inhibitor (PI), either bortezomib or carfilzomib. On occasion, doxorubicin is also omitted because of patient history and provider preference.
PATIENTS AND METHODS
We retrospectively reviewed the charts of adult patients with MM receiving mCAD regimens at our institution between 2012 and 2016 and analyzed utilization patterns, toxicity profiles, and clinical outcomes.
RESULTS
A total of 131 patients received mCAD, including 9% for newly diagnosed MM (NDMM), 18% attempting to optimize response to frontline therapy (OPT-MM), and 73% for treatment of relapsed/refractory MM (RRMM). Renal dysfunction was common; 31% had estimated glomerular filtration rate < 50 mL/min and 14% were dialysis dependent. The overall response rate was 83%, 63%, and 67% with a median progression-free survival of 17.4, 23.7, and 4.2 months, respectively, for NDMM, OPT-MM, and RRMM. Median overall survival was not reached for NDMM or OPT-MM, and was 15.2 months for RRMM. Most patients (90%) bridged to subsequent therapy, including 32% who proceeded to autologous transplantation. Hematologic, infectious, and cardiac toxicities were common and were similar to those expected for cytotoxic chemotherapy.
CONCLUSION
mCAD regimens were safe and active across patient groups, including patients with renal dysfunction. Most patients were able to bridge to subsequent therapy.

Identifiants

pubmed: 32839138
pii: S2152-2650(20)30376-1
doi: 10.1016/j.clml.2020.07.015
pii:
doi:

Substances chimiques

Proteasome Inhibitors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e961-e985

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Rupa Narayan (R)

Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA.

Derek Galligan (D)

Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA.

Ann A Lazar (AA)

Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA.

Sarah Kim (S)

School of Pharmacy, University of California, San Francisco, San Francisco, CA.

Richard Fong (R)

School of Pharmacy, University of California, San Francisco, San Francisco, CA.

Marisela Tan (M)

School of Pharmacy, University of California, San Francisco, San Francisco, CA.

Mimi Lo (M)

School of Pharmacy, University of California, San Francisco, San Francisco, CA.

Shagun Arora (S)

Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA.

Nina Shah (N)

Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA.

Sandy W Wong (SW)

Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA.

Thomas Martin (T)

Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA.

Jeffrey Wolf (J)

Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA. Electronic address: Jeffrey.Wolf@ucsf.edu.

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Classifications MeSH