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

• Published in: Journal of geriatric oncology 2017-05, Vol.8 (3), p.165-169
• Main Authors: Tuchman, Sascha A, Moore, Joseph O, DeCastro, Carlos D, Li, Zhiguo, Sellars, Emily, Kang, Yubin, Long, Gwynn, Gasparetto, Cristina G
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Bortezomib - administration & dosage; Bortezomib - adverse effects; Chemotherapy; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Dose-Response Relationship, Drug; Early Termination of Clinical Trials; Elderly; Female; Frail; Geriatric Assessment; Hematology, Oncology and Palliative Medicine; Humans; Induction Chemotherapy - methods; Intention to Treat Analysis; Internal Medicine; Kaplan-Meier Estimate; Male; Multiple Myeloma - drug therapy; Multiple Myeloma - pathology; Myeloma; Risk Factors; Senior; Toxicity
• ISSN: 1879-4068; 1879-4076
• DOI: 10.1016/j.jgo.2017.02.004

Abstract 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 1.3 mg/m2 subcutaneously, cyclophosphamide 300 mg/m2 and dexamethasone 40 mg orally, all on days 1, 8, and 15 of a 28 day 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 24.2 months and OS 29.7 months, 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.