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Long-Term Follow-Up of a Phase II Trial of Vel/Dex in Frontline Therapy for Myeloma
By Sundar Jagannath, MD
12.17.06





Long-term follow-up of patients in this multi-center study demonstrates response rates of 90% overall, of which 40% were VGPR/CR. At two years, there is 85% overall survival. This regimen does not compromise stem cell harvest for auto transplant.

ABSTRACT:

Long-Term Follow-Up of Patients Treated with Bortezomib Alone and in Combination with Dexamethasone as Frontline Therapy for Multiple Myeloma. Session Type: Oral Session

Sundar Jagannath, Brian G.M. Durie, Jeffrey Lee Wolf, Elber S. Camacho, David Irwin, Jose Lutzky, Marti McKinley, Afshin Eli Gabayan, Amitabha Mazumder, John Crowley, Robert Vescio Medical Oncology, Aptium Oncology Research Network, Los Angeles, CA, USA; Cancer Research & Biostatistics, Seattle, WA, USA


Introduction: Novel therapeutic agents, such as bortezomib (VELCADE; btz), thalidomide, and lenalidomide, are being used in combination with dexamethasone (dex) as frontline therapies in MM. Phase 2 and 3 trials with limited follow-up have reported a high response rate and feasibility of high-dose therapy and stem cell transplantation (HDT-SCT). Here we present longer follow-up on our phase 2 trial of btzdex as frontline therapy. Methods: Patients (pts) with measurable disease and KPS 50% received btz 1.3mg/m2 on days 1, 4, 8 and 11 of a 3-week cycle for up to 6 cycles. Oral dex 40mg was added on the day of and day after btz for pts achieving < partial response (PR) after 2 cycles or < complete response (CR) after 4 cycles. Responses were assessed using European Group for Blood and Marrow Transplantation criteria, with the addition of near CR (nCR; CR but positive immunofixation). Results: 48 pts were accrued and were evaluable for response; a further 2 registered on the trial declined to proceed. Median age was 60 years, 46% were male, 64% had IgG and 21% IgA, and 50% were DurieSalmon stage III. At the end of btzdex treatment, overall response rate (ORR; CR+nCR+PR) was 90% with 19% CR/nCR; an additional 8% achieved a minimal response (MR). Response to btz alone was rapid; response rate by end of cycle 2 was 50%, including 10% CR/nCR. Dex was added for 36 (75%) pts: 17 at cycle 3, 18 at cycle 5, and 1 at cycle 6. Addition of dex improved best responses to btz in 23 (64%) pts, with 12 improving from stable disease to MR or PR, 9 from MR to PR, 1 from PR to nCR, and 1 from nCR to CR. Median time to best response was 1.9 months. For all 48 pts, with a median follow-up of 24 months, median time to alternative therapy (TTAT) was 7 months (range: 225; this includes pts who went on to HDT-SCT), and median overall survival (OS) has not been reached; 1-year survival rate was 90%. For pts not proceeding to HDT-SCT, median TTAT was 22 months, median OS has not been reached; 1-year survival rate was 80%. 23/48 pts proceeded to HDT-SCT. Median CD34+ harvest was 12.6 x 106 cells/kg (range: 5.140.4 x 106) from a median of 2 collection days (range: 18). All pts had complete hematologic recovery; median time to neutrophil (ANC >1000/mm3) and platelet (>100,000/mm3) engraftment was 11 days (range: 813) and 17 days (range: 1098), respectively. In the 23 HDT-SCT pts, median TTAT and OS have not been reached; post-transplant 1-year survival rate was 90%. The most common grade 2 adverse events for btzdex were sensory neuropathy/neuropathic pain (37%), fatigue (20%), constipation (16%), nausea (12%), and neutropenia (12%). Two pts developed grade 4 events (1 neutropenia, 1 thrombocytopenia).Conclusion: Btzdex is an effective frontline therapy for MM, with an ORR of 90%, including 19% CR/nCR, and OS rate of 80% at 1 year. The treatment is well tolerated and toxicities were manageable and reversible. Addition of dex to btz provides improved responses. TTAT for patients not undergoing HDT-SCT was 22 months. The regimen does not prejudice subsequent HDT-SCT; stem cell harvest and engraftment were successful in all pts proceeding to transplant. Consolidation with HDT-SCT further increases the response rate and durability of response. Btz+dex is being compared to VAD as induction therapy prior to HDT-SCT in a phase 3 study.
Abstract #796 appears in Blood, Volume 108, issue 11, November 16, 2006


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