Combination therapy based on bortezomib for 102 patients with newly-diagnosed multiple myeloma: a Chinese experience
Authors: He Jingsong , Yang Li , Han Xiaoyan , Zheng Gaofeng , Meng Xiaojian , Wei Guoqing , Wu Wenjun , Zheng Weiyan , Ye Xiujin , Shi Jimin , Xie Wanzhuo , Zhang Jie , Huang He , Lin Maofang , Cai Zhen 
Published: October 2019

Abstract
Abstract 5116
Multiple myeloma (MM) is a malignant neoplasm of plasma. The rates of complete remission (CR) or very good partial remission (VGPR) for patients received conventional chemotherapy are still low with median overall survival about 3 years. Here we report our results with combination therapy based on bortezomib in the Chinese population and investigat the efficacy and safety of Bortezomib-based therapies in previously untreated MM patients.

Metohds:
Between 1st Feb. 2006 and 31st Dec. 2010, 102 consecutive newly-diagnosed patients with symptomatic MM were treated with combination therapies based on bortezomib. Sixty-four patients were male and 38 were female. Median age was 59 years (range 31–86 years). Forty-two patients were stage 3 according to the International Staging System, 36 patients were stage 2 and 24 patients were stage 1. The combinations included dexamethasone (BD group ), dexamethasone plus subsequent thalidomide (BDT group ) and dexamethasone plus cyclophosphamide (BDC group ) or epirubicin (BDA group ) based on bortezomib. Thirty-five patients were in BDT group, 19 in BD group, 32 in BDC group and 16 in BDA. All patients received a median of three cycles of therapy (range 1–5 ). The IMWG criteria was used for response evaluation and toxicities were evluated according to the NCI Common Toxicity Criteria version 3.

Results:
The efficacy of the triplet combination therapy based on bortezomib including BDT, BCD and BAD were better than BD group, with response rate greater than or equal to partial remission(≥PR) 85.7%, 90.6%, 93.7% and 68.4%, respectively. The efficacy of BDA and BDC group were significantly superior to BD group (P=0.048,0.050). Bortezomib in combination with chemotherapy was highly effective as treatment for symptomatic multiple myeloma, even only after one cycle. The efficacy for patients received one cycle of BDT, BD, BCD and BAD was 65.7%, 42.1%, 65.6% and 62.5%, respectively. Patients treated with BD had suboptimal responses to those received BDT, BCD and BAD treatment and one cycle of BCD was superior to one cycle of BD (P=0.019).The median follow-up time was 17m (1–60m), including 31m (1–60m) for 35 patients in BDT group and 16m (2–29m) for the remaining 67 patients. The median progression-free survival (PFS ) of BDT group was 15m (9.8–20.2m ) while BD group was 12m (8.1–15.8m), BCD group was 13m (5.9–20.1m ), and BAD group was 12m (7.8–16.2m ), without significant difference. The median overall survival (OS ) of BDT group was 35m (13.2–56.8m ) while BD, BCD and BAD groups was not reached yet. There was no significant difference in OS among groups, but BCD and BAD were superior to BD group (P=0.104, 0.142 ). The frequent treatment-emergent adverse events includes hematologic adverse events such as neutropenia, anemia, thrombocytopenia and the non-hematologic adverse events like fatigue, infection, constipation, diarrhea, pleural effusion and ascites, herpes zoster and peripheral neuropathy. Patients treated with BDT were more likely to show peripheral neuropathy than those treated with BD, BCD and BAD (91.4% vs 73.6%, 68.7%, 74.9% ), but there is no statistical significant difference (P = 0.131), Grade 2 or 3 peripheral neuropathy was occurred in 45.7% of BDT group significantly higher than BD, BCD and BAD groups. (21.0%, 15.7% and 18.7%, P = 0.028 ). Other related adverse events in all the groups had no significant difference. Routine anticoagulation or anti-thrombsis were not used. Only 1 patient suffered from DVT/PE but did well with treatment.

Conclusions:
Our preliminary experience in Chinese patients indicated that combination chemotherapy based on bortezomib is highly effective in newly-diagnosed multiple myeloma and BDC, BDA or BDT regimens may be more superior to BD in Chinese population. There were relative lower rates of DVT/PE in the Chinese patients with MM received combination chemotherapy based on bortezomib.

Disclosures:
No relevant conflicts of interest to declare.