A Retrospective Study Of The Correlation Between Bortezomib Based Chemotherapy Regimens,Cytogenetic Characteristics And Treatment Response And Prognosis Of Multiple Myeloma

Objective:The study is aimed at exploring the effect of bortezomib based combination chemotherapy regimens, their impact on patients’ survival; impact that cytogenetic abnormalities detected by FISH method have on patients’ treatment effect, survival and treatment response.Method:212newly diagnosed multiple myeloma patients treated at the author’s center from Jan2006to Mar2014were divided into four treatment groups:34cases of BDT regimen,44cases of BD regimen,76cases of BCD regimen and58cases of BAD regimen.76cases underwent FISH examination to detect cytogenetic abnormalities. Treatment response and survival was observed. Among all212patients, median follow-up time was23months (2-81months). Median follow-up time for BAD group was21months (3-81months), for BCD group was20.5months (3-72months), for BD group was23months (2-72months), and for BDT group was37.5months (12-64months).Result:(1) All patients underwent median cycle of3cycles (1-8cycles), overall response (above PR) case number was196, ORE. was91.2%, among which77cases (36.3%) achieved PR,119(55.3%) achieved VGPR or above, and33cases (23%) achieved CR/nCR. ORR for BAD, BCD, BD and BDT group are96.6%,94.7%,77.8%, and90.9%(x2=10.949, P=0.008), respectively; rates above VGPR were60.3%,57.9%,42.1%, and57.6%(x2=3.937, P=0.263), respectively; CR rates were32.8%,28.9%,13.3%, and33.3%(x2=6.397, P=0.093), respectively. The results suggest that treatment response was significantly higher in three-drug regimens than in two-drug regimens.(2)After one cycle of treatment,166patients had response (the response evaluation is PR or above), and the ORR is77.2%, among which134cases (63.2%) achieved PR and32cases (14.9%) achieved VGPR or above. ORR for BAD, BCD, BD and BDT group were82.8%,80.3%,53.3%and90.9%(x2=17.444, P=0.000), respectively; rates above VGPR were31.0%,10.5%,8.9%, and6.1%(x2=13.926, P=0.003), respectively. The results suggest after one cycle of treatment, the treatment response was already significantly higher in three-drug regimens than in two-drug regimens.(3) Median PFS of212patients was23months (95%CI:18.9-27. lmonths). Median PFS of BAD group is16months (95%CI:2.4-29.6months); median PFS of BCD group is23months (95%CI:13.3-32.7months); median PFS of BD group is16months (95%CI:11.2-20.8months); median PFS of BDT group is36months. Difference among treatment groups had borderline significance (x2=7.415, P=0.064). Median PFS for older patients group (age65years or older) was12months(95%CI:9.7-14.3months), and median PFS for younger patients group (below65years) was29months (95%CI:24.2-33.8months), the difference was statistically significant (x2=15.077, P=0.000). Median OS for BCD group was57months (95%CI:17.7-96.3months) and median OS for BDT group was36months. OS for other groups have not reached. The difference among groups was non-significant. In patients with different age groups, median OS for older patients was31months (95%CI:24.3-37.7), while median OS for younger patients group had not reached. The difference was statistically significant (x2=12.979, P=0.000). Thus the results suggest treatment regimens have significant impact on PFS, and PFS and OS of younger patients are significantly higher than that in older patients.(4) FISH method detected33cases (43.4%) of17p13abnormality,26cases (34.2%) cases of13q14abnormality,15cases (19.7%) of1q21abnormality,21cases (27.6%) of14q32abnormality and36cases (47.4%) of13q14.3abnormality. Multiple abnormalities coexistence occurs in part of the patients, and the total positive rate is77.6%.(5)17pl3abnormality is negatively correlated with hemoglobulin level (P<0.05),1q21abnormality is negatively correlated with serum albumin level (P<0.05),13q14abnormality is positively correlated with LDH level (P<0.05) and negatively correlated with PFS (P<0.05), and14q32abnormality is negatively correlated with PFS (P<0.05).(6) When17p13is normal, triplet regimens are superior to doublet regimen in OS (not reached)(x2=3.583, P=0.012), however when abnormal, the difference is statistically non-significant (P>0.05). When both17p13and1q21are normal, triplet regimens are significantly superior to doublet regimens in OS (P=0.024), however when at least one of the two is abnormal, the difference is non-significant (P>0.05).Conclusion:The response rate of newly diagnosed multiple myeloma patients are significantly better in those treated with bortezomib based triplet regimens (BAD, BCD and BDT) than doublet regimen. Triplet regimens are superior than doublet regimen in PFS, however have no significant impact in OS; and younger patients had both longer PFS and OS than older patients. In patients with both normal17pl3and1q21, triplet regimens have OS superiority, while when either is abnormal, the OS superiority diminishes. It implies that the result of FISH test may predict drug resistance.