Bortezomib in relapsed multiple myeloma: response rates and duration of response are independent of a chromosome 13q-deletion

Abstract

Studies of bortezomib in patients with relapsed multiple myeloma (MM) suggested that bortezomib may be active even in the presence of adverse prognostic factors. We therefore evaluated 62 patients with relapsed/refractory MM who were treated with single-agent bortezomib, and addressed the question whether or not the negative prognostic impact of unfavorable cytogenetic abnormalities may be overcome by bortezomib. By interphase fluorescence in situ hybridization (FISH), a deletion of chromosome 13q14 [del(13q14)] was present in 33 patients (53%). Overall response rates to bortezomib were similar in patients with and without del(13q14) (45 versus 55%; P ¼ 0.66), and rates of complete remission (CR) near CR were also not different between the two patient populations (18 versus 14%). Three patients had a t(4;14)(p16;q32) in addition to del(13q14), and all of them had a 450% paraprotein reduction. Median duration of response was 12.3 months in patients with del(13q14) compared with 9.3 months in patients with normal 13q-status (P ¼ 0.25), and survival was also not different between the two patient populations. Patients not benefiting from single-agent bortezomib were characterized by the combined presence of a del(13q14) and low serum albumin (median survival 4.6 months). Our results provide evidence for remarkable activity of bortezomib in MM with del(13q14). Patients who do not respond to bortezomib and consecutively have short time to treatment failure and overall survival can be identified by low serum albumin in addition to del(13q14) and should be considered for bortezomib combinations.

Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexaméthasone

“…In relapsed or refractory MM patients with del(13), outcomes reported here for lenalidomide and dexamethasone are comparable with those reported for bortezomib in a consecutive patient Lenalidomide and cytogenetics in myeloma H Avet-Loiseau et al cohort (ORR 45%; OS 9.9 months) 17 and in a retrospective analysis of the SUMMIT (ORR 24%; OS 10.0 months) and APEX (ORR 20-53%; OS 10.0 months to not reached) trials. 18 In the consecutive patient cohort, the authors reported no significant difference in outcomes between patients with and without del(13); however, median time from initiation of first-line therapy was significantly shorter in patients with than without del(13) (26 months vs 51 months; P ¼ 0.02).…”

“…18 In the consecutive patient cohort, the authors reported no significant difference in outcomes between patients with and without del(13); however, median time from initiation of first-line therapy was significantly shorter in patients with than without del(13) (26 months vs 51 months; P ¼ 0.02). 17 In the retrospective analysis, prognosis appeared to be poorer in patients with del(13) in both studies, but the differences were not statistically significant in the matched-pairs analyses (selected groups of patients balanced for age and ISS parameters). 18 Our study adds new data with regard to the prognostic value of high-risk cytogenetic abnormalities in relapsed or refractory MM treated with novel therapies.…”

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials

“…Our results could also be explained by the recent availability over our study period of time of novel therapeutic agents at the time of the relapse. Preliminary data suggest that bortezomib 26 or lenalidomide 27 could be the treatment of choice in this situation. New targeted therapies such as FGFR3 inhibitor currently evaluated in prospective protocols could also improve the outcome of this aggressive disease in patients expressing FGFR3.…”

Clinical Impact of Bortezomib in Frontline Regimens for Patients with Multiple Myeloma

“…In other studies in the relapsed setting, bortezomib has been shown to be active with a similar toxicity profile in patients with chromosome 13 deletion [32,33], and in patients with renal dysfunction or renal failure requiring dialysis [34 -36].…”