Multiple myeloma is an incurable B-cell hematologic malignancy managed by combination systemic therapy of bortezomib, liposomal doxorubicin, and dexamethasone (VDD).
The multi-agent combination demonstrated significant anti-myeloma activity in relapsed/ refractory disease; however, the management of patients with high-risk myeloma remains a challenge.
Investigators conducted a phase 1 and 2 trial to evaluate whether the incorporation of an alkylator, cyclophosphamide, to VDD (CVDD) may increase response and improve long term outcome in newly diagnosed both standard-risk and high-risk patients with multiple myeloma.
The primary objective of the phase 1 study was to evaluate the safety and tolerability of maximum planned dose (MPD) and the phase 2 was to assess the overall response rate. There were 49 patients treated at MPD, and patients received 6-8 cycles of CVDD at four dose levels.
Of the 49 patients, 22% had high-risk multiple myeloma. The overall response and complete response rates were 91% and 26% in standard-risk, and 100% and 58% in the high-risk cohort, respectively. The median progression-free survival was 31.3 months after a median follow-up of 34 months.
Overall, the four-drug combination, CVDD, was well tolerated and produced high quality response in newly diagnosed multiple myeloma patients. The authors conclude that all patients after CVDD induction therapy can safely and successfully undergo stem cell mobilization and collection.
The authors conducted a phase 1/2 trial evaluating the combination of cyclophosphamide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone (CVDD) for newly diagnosed multiple myeloma (MM). The 2-year overall survival was 91.1% in the standard-risk and 88.9% in the high-risk cohort, respectively.