Doxorubicin Hydrochloride, Lenalidomide, and Dexamethasone versus Bortezomib, Lenalidomide, and Dexamethasone Prior to Scheduled Stem-Cell Transplant in Newly Diagnosed Myeloma
Although autologous stem-cell transplant (SCT) remains a standard of care in younger patients with newly diagnosed multiple myeloma (MM), chemotherapy induction triplets with 1 of the newer compounds is currently recommended prior to SCT. Studies have shown that the chemotherapy induction triplet of bortezomib (V), lenalidomide (R), and dexamethasone (D; VRD) ranks among the most effective treatments for these patients at this stage. This chemotherapy induction triplet plus SCT has shown superior efficacy over chemotherapy alone. The DSMM XIV study researchers look to examine RAD triplet therapy: RD and Adriamycin (doxorubicin) plus SCT versus VRD induction therapy in patients with newly diagnosed MM.
The DSMM XIV study was set up using a double 2 x 2 factorial design to enroll patients with newly diagnosed MM who were up to 65 years of age. The efficacy end point for the initial study phase was postinduction (PI) complete response (CR) rate. The researchers hypothesized that the CR rate with RAD would be noninferior to an estimated 20% CR with VRD. The study was powered to confirm the noninferiority of RAD at a 10% margin, with a one-sided α level of 0.05.
A total of 476 patients were included in this study, with a median age of 55 years (range, 32-65 years). Of them, 469 patients were randomized to receive at least 1 dose of the study drug. Baseline characteristics were well-balanced between the 2 groups. Patients were randomized to receive either 3 four-week RAD cycles (n = 232) or 3 three-week VRD cycles (n = 237). A total of 89.7% of the patients receiving RAD versus 93.2% of patients receiving VRD completed all induction therapy cycles. The PI CR rate was 11.8% with RAD versus 13.0% with VRD (P = 0.697). The number of patients experiencing treatment-emergent serious adverse events was statistically similar in the 2 groups (P = 0.144). Overall mortality was 0.2%. The end point was met with comparable PI CR rates for RAD and VRD, respectively.
Although this study may be the first to compare 2 lenalidomide-based triplets prior to SCT in patients with newly diagnosed MM, additional studies are necessary to better understand the time-dependent end points of the pretransplant induction regimens.
Knop S, et al. ASCO Abstract 8001.