Phase II study of dose-attenuated bortezomib, cyclophosphamide and dexamethasone ("VCD-Lite") in very old or otherwise toxicity-vulnerable adults with newly diagnosed multiple myeloma.

OBJECTIVES: Multiple myeloma (MM) primarily strikes older adults, but full-dose chemotherapy such as bortezomib (Velcade), cyclophosphamide and dexamethasone (VCD) is often excessively toxic to very old or frail adults and those with substantial comorbidities. We piloted dose-attenuated VCD ("VCD-Lite") in such vulnerable adults with newly diagnosed MM (NDMM). MATERIALS AND METHODS: Subjects with NDMM and a high risk of therapy-related toxicity due to factors above received bortezomib 1.3mg/m2 subcutaneously, cyclophosphamide 300mg/m2 and dexamethasone 40mg orally, all on days 1, 8, and 15 of a 28day cycle for eight cycles, followed by indefinite, alternating bortezomib and lenalidomide maintenance. Toxicity, overall response rate (ORR), progression-free and overall survival (PFS and OS) were determined. The Cancer and Aging Research Group geriatric assessment (CARG GA) was administered at baseline in an exploratory manner as a predictor of severe toxicity. RESULTS: 14 patients went on the study, which was closed early due to slow accrual. Intention-to-treat ORR was 64%. 64% of patients experienced grade ≥3 adverse events, the majority of which were unlikely therapy-related. Median PFS was 24.2months and OS 29.7months, with 14%, 36% and 29% of patients discontinuing study drugs due to toxicity, MM progression and other reasons respectively. Baseline CARG GA was successfully completed by all subjects but one. CONCLUSION: VCD-Lite is a viable option for vulnerable adults with NDMM. CARG GA is feasible. Further studies to optimize therapy and to explore CARG GA as a toxicity predictor are vital.

Duke Scholars

Author Carlos Manuel de Castro III Medicine, Hematologic Malignancies and Cellular Therapy

Author Joseph Odell Moore Medicine, Hematological Malignancies

Author Zhiguo Li Biostatistics & Bioinformatics, Division of Biostatistics

Author Yubin Kang Medicine, Hematologic Malignancies and Cellular Therapy

Author Gwynn Douglas Long Medicine, Hematologic Malignancies and Cellular Therapy

Author Cristina Gasparetto Medicine, Hematologic Malignancies and Cellular Therapy