Bortezomib and Pegylated Liposomal Doxorubicin as Induction Therapy for Adult Patients with Symptomatic Multiple Myeloma: Cancer and Leukemia Group B Study 10301.

Introduction: The proteasome inhibitor bortezomib in combination with pegylated, liposomal doxorubicin (PLD) has significant activity against relapsed/refractory multiple myeloma (MM). It was therefore of interest to evaluate this combination in previously untreated MM patients (pts) requiring induction chemotherapy.

Methods: Patients enrolled onto Cancer and Leukemia Group B study 10301 received bortezomib at 1.3 mg/m² on days 1, 4, 8, and 11 of every 21 day cycle, along with PLD at 30 mg/m² on day 4, for a maximum of eight cycles. Primary objectives were to determine the complete response (CR) + near-CR rate, and also to define the toxicity of this regimen in the front line setting. Secondary objectives included determining the overall response rate, the ability to collect stem cells, and the time to progression and overall survival.

Results: Between June, 2004, and October, 2005, a total of 63 pts were enrolled. Adverse event (AE) data were available for 55 pts, with hematologic AEs reaching grade 3 in 14 pts (25%), and grade 4 in 5 pts (9%). Notable hematologic AEs included neutropenia (grade 3 in 16%, and grade 4 in 2% of pts), thrombocytopenia (9% and 5%, respectively), lymphopenia (11% and 2%), and anemia (7% and 2%), though there was only one episode of febrile neutropenia. Non-hematologic toxicities reaching grade 3 were seen in 32 pts (58%), while 5 pts (9%) had grade 4 non-hematologic toxicities. Fatigue (grade 3 in 16%, grade 4 in 0%), sensory neuropathy (11% and 2%, respectively), hand-foot syndrome (9% and 0%), syncope (9% and 0%), motor neuropathy (7% and 0%), dehydration (7% and 0%), rash (7% and 0%), weight loss (5% and 0%), hypotension (5% and 0%), diarrhea (5% and 0%), nausea (5% and 0%), infection (5% and 0%), and dyspnea (5% and 0%) were notable AEs seen in 5% or more of pts. Preliminary response data were available for 57 pts, of whom 9 (16%) achieved a CR or near-CR, while 58% attained at least a partial response (PR). Final response data were available for 29 pts who completed their study-directed therapy, and among these the CR + near-CR rate was 28%, with an overall response rate (PR or better) of 79% in this small cohort. Progression-free and overall survival can not yet be estimated because of a paucity of events at a median of 10 months of follow-up. Stem cell collection data is available for 6 pts after induction therapy with bortezomib and PLD, in whom a median of 13.6 x 10⁶ CD34⁺ cells/kilogram were mobilized (range 11.2 – 48.6 x 10⁶).

Conclusions: These preliminary data suggest that bortezomib and PLD is well-tolerated by chemotherapy-naïve multiple myeloma patients in this study. Moreover, this steroid-free regimen has promising activity, and does not seem to compromise the ability to collect stem cells for later transplantation.