Improved Response Rates with Bortezomib in Relapsed or Refractory Multiple Myeloma: An Observational Study in Chinese Patients

Abstract

IntroductionBortezomib, a novel proteasome inhibitor, is approved for the treatment of relapsed multiple myeloma (MM). Efficacy and safety of bortezomib is well known; however, it was necessary to validate the data in patients with different ethnic backgrounds. The efficacy and safety of bortezomib was assessed in patients from China with relapsed/refractory MM in a real-world scenario.MethodsThis prospective, non-interventional, observational study enrolled both male and female Chinese patients, aged ≥18 years and diagnosed with relapsed or refractory MM. Administration of intravenous bortezomib at 1.3 mg/m2 was recommended twice a week for 2 weeks (days 1, 4, 8 and 11), followed by a 10-day rest period (maximum of 8 cycles) and a follow-up every 12 weeks for 3 years. Efficacy assessments included best response, objective response rate (ORR), time to response, duration of response, and overall survival. Safety was also assessed.ResultsA total of 517 patients were enrolled with a median age of 58.7 years. Patients predominantly had immunoglobulin G type (46.2%) and stage III (47.8%) myeloma. Overall, 202 (42.3%) patients had partial response as best response, ORR was 88.9% and the proportion of patients exhibiting complete response was 24.7%. The median time to response observed was 27 (21–40) days. Median time to progression was 415 days and median overall survival was 475 days. Thrombocytopenia (14.4%) was the most common adverse event.ConclusionBortezomib demonstrated clinical response in majority of patients and was well tolerated in this observational study in Chinese patients with relapsed/refractory MM.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-014-0159-z) contains supplementary material, which is available to authorized users.

Bortezomib therapy in a real-world setting in patients with relapsed or refractory multiple myeloma

“…Of the evaluable Taiwanese patients with MM, the majority demonstrated PR; this is consistent with earlier studies in Asian population (25%-42%). 22,23 Furthermore, although SD status was not achieved in most patients, those demonstrating PD were notably few. These findings are consistent with global and Asian studies, 20,22,23 which supports the therapeutic advantage of bortezomib when introduced early as salvage treatment in the course of disease.…”

“…22,23 Furthermore, although SD status was not achieved in most patients, those demonstrating PD were notably few. These findings are consistent with global and Asian studies, 20,22,23 which supports the therapeutic advantage of bortezomib when introduced early as salvage treatment in the course of disease. It should be noted here that although studies have demonstrated that higher response quality is associated with longer response duration and survival, 26-28 not all studies show an absolute benefit of achieving CR, and there may exist a subgroup of patients who may obtain prolonged survival often without ever achieving CR.…”

“…17,18 Several studies have established the efficacy and safety of bortezomib in the Caucasians, 10,11,13,19-21 and Asians. 22,23 However, as clinical trials are restrictive in their setup and design, 24 the current observational study was designed to simulate the real-world practice scenario and help insight into the therapeutic feasibility of bortezomib in Taiwanese patients with relapsed or refractory MM.…”

An inhibitor of ubiquitin conjugation and aggresome formation

“…However, in contrast to proteasome inhibitors, E1 enzyme inhibitors should not lead to the formation of aggresomes, which are known to limit the therapeutic efficacy of bortezomib and carlzomib in both hematological malignancies and solid tumors. [10][11][12][13][14][15][16][17][20][21][22][23][24] Specically, this paper reports the discovery of ABP A3, a dual inhibitor of the ubiquitin-and Nedd8-activating E1 enzymes, which inhibits both Nedd8-dependent and Nedd8-independent ubiquitin conjugation and protein degradation. We then used these probes to investigate the therapeutic potential of the UPS system to treat solid tumors using A549 cell line (non-small cell lung cancer) as a model system.…”

“…Furthermore, proteasome inhibitors have shown limited clinical efficacy in treating multiple myeloma. [10][11][12] These limited responses are in part due to the alternative degradation of misfolded proteins via the aggresomal pathway. [13][14][15][16][17] The aggresomal pathway clears misfolded proteins by delivering misfolded proteins to the lysosome, thereby alleviating proteotoxic stress and contributing to cell survival.…”