"The rational for the trial was based on a clinical trial that Dr. Keith Stewart performed in Toronto for relapsed myeloma patients. That preliminary study showed very high response rates for relapsed disease, and we took that same regimen and moved it upfront to newly diagnosed patients."
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 A Phase II Trial of Myeloma Induction Therapy with Cyclophosphamide, Bortezomib, and Dexamethasone (Cybor-D): Improved Response over Historical Lenalidomide-Dexamethasone Controls. Session Type: Poster Session, Board #820-III
Craig B. Reeder, Donna E. Reece, Rafael Fonseca, P. Leif Bergsagel, Joseph Hentz, Nicholas A. Pirooz, Jacy E. Boesiger, Jesus G. Pisa, Vishal Kukreti, Christine Chen, Suzanne Trudel, Joseph R. Mikhael, Martha Lacy, S. Vincent Rajkumar, A. Keith Stewart Hematology/Oncology, Mayo Clinic, Scottsdale, AZ, USA; Hematology/Oncology, Mayo Clinic, Rochester, MN, USA; Hematology/Oncology, Princess Margaret Hospital, Toronto, ON, Canada
Background: We previously reported an 85% response rate with 54% CR/nCR using a combination of cyclophosphamide (Cy), prednisone, and bortezomib (BZ) in relapsed myeloma (MM). We now report a Phase II clinical trial using a combination of Cy, BZ, and dexamethasone (Dex) [Cybor-D] in newly-diagnosed MM. We then compare the activity of this combination with historical controls treated with our current induction standard of Lenalidomide-Dexamethasone (L-Dex). Methods: 30 patients have been enrolled on Cybor-D. Treatment consists of Cy 300mg/m2 p.o. days 1, 8, 15, and 22; BZ 1.3 mg/m2 days 1, 4, 8, and 11, and Dex 40mg p.o. days 1-4, 9-12, 17-20. Prophylactic use of acyclovir, a quinolone and antifungal prophylaxis was highly recommended for all patients on study. Growth factors were allowed. As a relevant contemporaneous control for speed and depth of response, we used 33 patients treated on a recent Mayo Clinic trial of L-Dex (Rajkumar. Blood: 2005 106;4050-3). Response was defined according to IMWG criteria although in the current trial, bone marrows for confirmation of CR are not yet available on all patients. Results: At time of current analysis, 17 patients on Cybor-D were evaluable through at least one cycle for response and toxicity. Baseline characteristics included mean age of 57, 29% female, 41/24% ISS stage II/III. There were statistically more early stage patients on L-Dex; otherwise, baseline patient characteristics were similar. The mean % decline in monoclonal (M) protein from baseline following cycles 1-4 of Cybor-D were 71%, 90%, 93%, 96%. This compares favorably with L-Dex where equivalent % decline in M proteins were 66%, 77%, 80%, and 79%. Thus, in preliminary results, Cybor-D produces a more rapid initial decline and mean % reduction in M protein than L-Dex. Overall response rate ( PR) after one cycle of Cybor-D was 77% with 36% obtaining VGPR (L-Dex 73% and 18% respectively). The % of patients obtaining VGPR after each cycle was 36%, 64%, 77%, and 100% for Cybor-D as compared to 18%, 36%, 42%, and 33% for L-Dex. The overall VGPR at the end of four cycles of Cybor-D is currently100% ( 66%nCR using older nomeclature). Major toxicities grade 3 for Cybor-D included hematologic (37%), hyperglycemia (15%) and neuropathy (11%). Conclusions: In summary, for newly-diagnosed MM patients, four cycles of Cybor-D produces more frequent, rapid and deep responses when contrasted with historical L-Dex controls. Further confirmation of response rates and effect on TTP will be required.
Abstract #3601 appears in Blood, Volume 110, issue 11, November 16, 2007