Analysis Of Factors Associated With Improved Survival In Patients With Multiple Myeloma Over A 10-year Period In A Single Center

PART1 Analysis of long-term survival in multiple myeloma:a retrospective single-center study of 317 cases in ChinaObjective To investigate the clinical characteristics and prognostic factors in newly diagnosed multiple myeloma(NDMM)patients with long-term survival in China.Method NDMM patients diagnosed from July 2008 to July 2018 at Peking Medical College Hospital(PUMCH)were retrospectively analyzed,consisting of clinical characteristics,cytogenetic detection by fluorescence in situ hybridization(FISH),treatment and response.All patients were divided into 3 groups according to the overall survival(OS).G1 had OS less than 2 years,G2 with OS 2-5 years,G3 with OS more than 5years.Clinical and laboratory parameters were analyzed by multivariate regression statistical process and compared across different groups.Results There were 120,68,129 NDMM patients classified into G1,G2 and G3 groups respectively as a total of 317.Basic characteristics including age,gender,isotype of monoclonal protein were comparable in different groups.The G3 had significantly less patients with international staging system(ISS)Ⅲ(40.3%)and baseline hemoglobin less than 90g/L(32.6%),better kidney function and lower level of serum calcium than those in G1 and G2(P<0.05).The "double hit" myeloma was defined as both 1q21 + and 17p-.Any cytogenetic abnormality(CA)and "double hit" CAs were less detected in G3 patients.G3 showed significantly lower proportion of myeloma cells in bone marrow cytology than G1 and G2(G1 vs G2 vs G3,40.7±23.8%vs 41.2±26.4%vs 30.5±21.1%,PG1vsG3=0.004,PG2vsG3=0.011).The multivariate analysis suggested that elevation of lactic dehydrogenase(LDH),renal dysfunction,ISS,3 or more CAs and response depth were independent risk factors associated with early deaths.The median OS of cohort was 39.5 months.Compared with that of patients diagnosed before 2011,patients’ survival after 2013 was dramatically improved(pre-2011:37.67months,2011-2012:52.40 months,2013-2014:77.77 months,P<0.05)with less G1 patients(41%before 2011 to 20%in 2014,P=0.014).The ORR of front-line regimens in G1 group was 63.95%,which was statistically lower than that in G2(87.50%,P=0.001)or G3(96.63%,P<0.001).Similarly,fewer patients in G1 achieved very good partial response(VGPR)or better(29.06%),compared with G3(59.55%,P<0.001)or G2(45.31%,P=0.04).Conclusion MM patients with survival over 5 years have relatively less rate of ISS III,less cytogenetic abnormalities,lower LDH and better renal function.As anti-myeloma novel agents have become more accessible,early recognition of active disease and regular follow-up are key management strategies for further improvement of clinical outcome in the real world practice.PART 2 Analysis of cytogenetic abnormalities and prognosis in multiple myeloma:a retrospective single-center study of 359 cases in ChinaObjective To investigate the impact of cytogenetic abnormalities and specific chromosomal translocations involving immunoglobulin heavy-chain(IgH).Method From January 2015 to December 2018,a total of 359 newly diagnosed MM patients received FISH panel tests at Peking Union Medical College Hospital(PUMCH).The baseline data including age,gender,ISS stage,isotype of M protein,hemoglobin,LDH and serum calcium were collected.Clinical and laboratory parameters were analyzed by statistical process and compared between different groups.Results The cytogenetic abnormalities among patients are 1q21 gain in 148/359(41.2%)、del(13q14.3)in 161/359(44.8%)、del RB1 in 122/282(43.3%)、del(17p)in 41/359(11.4%)and IgH rearrangement in 145/359(40.4%).The estimated 2-year survival rates of the 1q21+ and 13q-groups were 80.2%and 81.3%,respectively.There was no significant difference in survival between patients with or without 1q21+/13q-(P value 0.229 and 0.596 respectively).Del(17p)has a negative impact on outcomes with a median OS of 43.47 months.IgH abnormalities rather than rearrangement were considered as negative IgH,including deletion,amplification etc.The proportion of negative IgH was 59.6%(214/359),among which 15.3%(55/359)patients were not rearrangements.Patients with t(14;undefined)accounted for 22.6%(81/359),t(11;14)and t(4;14)/t(14;16)occurred in 8.6%(31/359)and 9.2%(33/359)patients respectively.The estimated 2-year overall survival rates in negative IgH group,t(14;undefined)group,t(11;14)group were 63.6%,76.2%and 53.4%.The OS in patients with t(4;14)/t(14;16)was 31.53 months,which was significantly shorter than negative IgH group and t(14;undefined)group(P value 0.001 and 0.0006 respectively).Even though patients with t(11;14)had a shorter OS,it was not significant compared with negative IgH and t(14;undefined)(P value 0.190 and 0.091 respectively).The discrepancy of OS between four groups was significant(P<0.001).Among patients with an adverse IgH translocation 66.7%have gain(1q)and 27.3%have del(17p).The estimated 2-year survival rates of patients without or with a high-risk CA were 85.2%and 81.1%,respectively,with comparable clinical outcome(P=0.109).Double or triple combination of adverse IgH,gain(1q)and del(17p)is associated with worse survival,with a median OS of 31.53 months.Conclusion Cytogenetic abnormalities(CAs)like gain(1q)or del(17p)are more commonly seen in patients with t(4;14)/t(14;16)and patients with multiple adverse CAs have poor survival,while t(14;undefined)are not associated with worse prognosis.