Bortezomib appears to overcome poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials

Abstract

6501 Background: Deletion of chromosome 13 [del(13)] by conventional cytogenetics is an important adverse prognostic factor for survival in multiple myeloma (MM) patients (pts) regardless of treatment (conventional chemotherapy and autologous or mini-allogeneic transplantation). However, in a phase 2 trial with bortezomib (VELCADE) (SUMMIT), del(13) did not adversely affect survival or response rate (RR). Therefore, we wanted to support this observation in the recently concluded large phase 3 trial, APEX, which allowed us the opportunity to evaluate the prognostic value of del(13) in both the conventional treatment arm (dexamethasone, dex) and the bortezomib arm. Methods: The APEX trial was a randomized multi-center international phase 3 trial comparing bortezomib and high-dose dex in 669 pts with relapsed MM. This study demonstrated improved survival of pts on bortezomib vs those on dex. Metaphase cytogenetics (MCG) in 168 evaluable pts showed del(13) in 24 (14%). A match-paired analysis of 21 of the 24 evaluable del(13) pts with 41 pts with wild type chromosome 13 balanced for adverse prognostic factors (treatment, age, lines of prior therapy, β2M, and albumin) was performed to analyze the impact of del(13) on survival. Results: A significant decrease in survival was found in 21 evaluable pts with del(13) compared with 41 pts without this deletion [HR (95% CI) = 3.24 (1.27, 8.23), P = 0.0090]. Detection of del(13) was associated with markedly decreased survival in the dex arm [HR (95% CI) = 5.72 (1.65, 19.81), P = 0.0020]. In contrast, in the bortezomib arm, del(13) was not associated with a difference in survival [HR (95% CI) = 1.23 (0.26, 5.74), P = NS] or RR [25% del(13) vs 35%, P = NS]. Conclusions: Bortezomib therapy appears to overcome the adverse impact of del(13) on survival or response rate consistent with findings in SUMMIT. Del(13) by metaphase cytogenetics appears to remain an adverse prognostic factor for survival in the dex arm. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Millennium, Ortho-Biotech, Pharmion Amgen, Celgene, Millennium, Ortho-Biotech, Roche Millennium