1q21+ Is Associated with Poor Prognosis in Newly Diagnosed Multiple Myeloma Patients with Extramedullary Disease: A Retrospective Study

Abstract:

Background: 1q21+ is a common cytogenetic abnormality in multiple myeloma (MM) and is considered as an independent factor for poor prognosis, but its impact on extramedullary disease (EMD) remains unknown.

Method: In our retrospective analysis, patients who met the diagnostic criteria of IMWG and first diagnosed with EMD from January 2011 to May 2022 were enrolled in the study. EMD patients were divided into 2 subgroups: 1q21+ and 1q21- according to the FISH analysis. 1q21+ abnormality was regarded as gain of 1q21 (gain [1q21], 3 copies) and amplification of 1q21 (amp [1q21], ≥4 copies). Continuous variables were analyzed by independent-sample t test or Mann-Whitney U test and categorical variables were compared using chi-square test or Fisher's exact test. Kaplan-Meier method was applied for PFS and OS curve made and differences were evaluated by Log-rank test. Cox proportional hazard models were constructed for prognostic factors analyze.

Result: Patients with 1q21+ presented with advanced International Staging System stages (stage III percentage: 68.2% vs. 30.0%, P=0.006), lower level of hemoglobin (91g/dL vs. 113.5g/dL, P=0.004), higher tumor burden (BMPC infiltration≥50% : 45.0% vs. 11.9%, P＜0.001), higher level of serum β2-microglobulin (7.24 g/L vs. 3.85 g/L, P=0.003) and lactic dehydrogenase (LDH) (206.5 U/L vs. 177 U/L, P=0.019). Higher incidence of soft tissue related EMD (54.5% vs. 18.6%, P＜0.001), renal dysfunction (50.5% vs. 17.7%, P=0.002) and hypercalcemia (27.3% vs. 7.1%, P=0.011) was also observed in 1q21+ subgroup. 1q21+ was found to be strongly associated with other high risk cytogenetic abnormalities including IgH/FGFR3 translocation (22.7% vs. 4.3%, P=0.007) and IgH/MAF translocation (22.7% vs. 1.4%, P＜0.001). Patients with 1q21+ had a significantly shorter overall survival (OS) and progression-free survival (PFS) (OS: 24 months vs. 47 months, P=0.002; PFS: 14months vs. 38months, P＜0.001), and the poor survival outcome couldn't be reversed by autologous hematopoietic stem cell transplantation (auto-HSCT). Further investigation estimated the impact of cooccurrence of 1q21+ and del17p on survival outcome. For median OS, 1q21- patients without del17p was 47 months, 1q21+ patients without del17p were 28 months, 1q21- patients with del17p was 22 months, and patients presented with both 1q21+ and del17p was 18 months (p=0.02). The median PFS for 1q21- without del17p, 1q21+ without del17p, 1q21+ with del17p was 38 months, 20 months and 6.5 months respectively, while not reached for 1q21- patients (P＜0.001). Multivariate analysis suggested 1q21+ along with EMD-S, elevated LDH level and P53 deletion were independent risk factors for poor prognosis in EMD patients. For 1q21+ EMD patients, hypercalcemia, elevated LDH level and P53 deletion were defined as independent adverse risk prognostic factors.

Conclusion: Taken together, our findings emphasized that 1q21+ increased the possibility of disease progression and predicted poor survival in EMD patients. 1q21+ EMD tends to be associated with other high risk disease factors. ASCT may not overcome the adverse effect of 1q21+ in EMD patients. We suggested 1q21+ should be considered as a high-risk factor and added into routine assessment of risk stratification in EMD patients.