A prospective, open-label, multicenter, observational study to evaluate the efficacy and safety of bortezomib-melphalan-prednisone as initial treatment for autologous stem cell transplantation-ineligible patients with multiple myeloma

Abstract

Bortezomib-melphalan-prednisone (VMP) showed superior efficacy versus MP as first-line treatment for transplantation-ineligible multiple myeloma (MM). This study investigated the efficacy of VMP for Korean patients with MM.Overall, 177 MM patients received 9 cycles of VMP in this prospective, multicenter, observational study. The primary endpoint was 2-year progression-free survival (PFS).Thirty-nine (22%) patients were aged ≥ 75 years and 83 (47.4%) patients had International Staging System stage III. A median of 5 cycles were delivered. Overall response rate (ORR) was 72.9%, and complete response (CR) rate was 20.3%. With a median follow-up of 11.9 months, median PFS was 17 months. The 2-year PFS and overall survival (OS) rates were 29.2% and 80.0%, respectively. Median OS was not reached. PFS was significantly different depending on performance status (Eastern Cooperative Oncology Group < 2 vs. ≥ 2; p = 0.0002), β2-microglobulin level (< 5.5 vs. ≥ 5.5 mg/L; p = 0.0481), and cumulative dose of bortezomib (< 35.1 vs. ≥ 35.1 mg/m2; p < 0001). The common adverse events (AEs) were in line with the well-known toxicity profiles associated with VMP.In conclusion, VMP is a feasible and effective front-line treatment for transplant-ineligible older patients with MM in Korea. Continuing therapy with prompt adjustment of treatment according to AEs may be important to improve outcomes of elderly patients.

Modified dose of melphalan-prednisone in multiple myeloma patients receiving bortezomib plus melphalan-prednisone treatment

“…The recorded CRR of 30.5% is comparable that of approximately 30% observed in previous studies [4,14]. Moreover, our CRR was higher than that obtained in another Korean study with similar baseline characteristics and a Japanese study (22% and 19%, respectively), and our ORR of 81.0% was also higher than that obtained in these two studies [7,13]. In addition to the cumulative dose, the median dose intensity for bortezomib in this study (8.1 mg/m 2 /cycle) is comparable to that of the VISTA study (8.32 mg/m 2 /cycle) and higher than that of the aforementioned Japanese study (6.86 mg/m 2 /cycle) [13].…”

“…The largest component of grade 3 to 4 or greater non-hematologic toxicities was infection (15.3%), and pneumonia was the most common cause of the discontinuation of treatment. Incidences of peripheral neuropathy and herpes zoster were found to be relatively lower than those reported in previous studies [4,7,13,14]. The relatively lower incidence of peripheral neuropathy in this study might have been due to the change to subcutaneous bortezomib administration from an early period in the study and also weekly dosing.…”

“…Currently there are no appropriate guidelines regarding whether or how doses of MP or bortezomib should be reduced when adverse events occur during VMP treatment. Recently, some studies have indicated that a higher cumulative dose of bortezomib can lead to improved OS [6,7]; however, there are no comparable data regarding the dose intensity of MP. The aim of this study was therefore to investigate the clinical outcomes of modifying the MP dose in MM patients compared with the regularly planned MP dose from the beginning of VMP treatment.…”

Overexpression of HIF-1α contributes to melphalan resistance in multiple myeloma cells by activation of ERK1/2, Akt, and NF-κB

“…Melphalan, an alkylating agent, in combination with predonisolone has been used as first-line therapy in patients with MM and has proven effective in MM therapy in non-transplant candidates. In addition, a combination of melphalan and predonisolone plus bortezomib or lenalidomaide/thalidomide prolongs overall survival in patients with MM [12][13][14][15]. Furthermore, a combination of dratumumab, bortezomib, melphalan, and predonisolone (daratumab group) increases the progression-free survival (PFS) of patients in 18 months relatively to bortezomib, melphalan, and predonisolone…”

Frontline therapy for newly diagnosed patients with multiple myeloma

“…Serious adverse events developed in 68.4% of patients, 14.7% of which resulted in death. Development of peripheral neuropathy was the leading cause of discontinuation [39]. Therefore, bortezomib must be injected subcutaneously to decrease peripheral neuropathy, and early dose adjustment including weekly injection of bortezomib is essential according to frailty status and adverse events.…”