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

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2020-12, Vol.20 (12), p.e961-e985
• Main Authors: Narayan, Rupa, Galligan, Derek, Lazar, Ann A., Kim, Sarah, Fong, Richard, Tan, Marisela, Lo, Mimi, Arora, Shagun, Shah, Nina, Wong, Sandy W., Martin, Thomas, Wolf, Jeffrey
• Format: Article
• Language: English
• Subjects: Bortezomib; Carfilzomib; Chemotherapy; Renal failure; Renal insufficiency
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/j.clml.2020.07.015

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. Cytotoxic chemotherapy is often used for aggressive or relapsed/refractory multiple myeloma. We retrospectively studied the clinical outcomes of 131 patients who received modified hyper-CVAD with or without proteasome inhibitors (mCAD) for multiple myeloma. We found that mCAD regimens were often used by providers for clinical stabilization and as a bridge to future therapy, including autologous stem cell transplantation.