P981: DISEASE CHARACTERISTICS AND TREATMENT OUTCOMES OF MYELOMA PATIENTS <50 YEARS OF AGE: AN ANALYSIS OF THE BALKAN MYELOMA STUDY GROUP

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Multiple myeloma (MM) is a rare malignancy among young individuals; median age of diagnosis is ~70 years and MM frequency in ages below 50 is low. Disease characteristics, prognostic factors and outcomes of young MM patients (pts) are not well described. In addition, new advances in the treatment of MM may have different effects on the outcomes of younger compared to older pts. Aims: to describe baseline disease characteristics, outcomes and prognostic factors for overall survival (OS) in MM pts <50 years of age, using data available in the Balkan Myeloma Study Group registry. Methods: We analyzed the outcomes of 350 consecutive pts <50 years of age treated within centers of the BMSG. Results: This group included 10.4% (1.8% were <40 years) of MM pts in the registry and their median age was 45 years (range 26-49). At the time of diagnosis anemia (hemoglobin<10 gr/dl) was present in 37%, renal impairment (RI) (eGFR<60 ml/min/1.73 m2) in 27% and severe RI (<30 ml/min/1.73 m2 or requiring dialysis) in 8.5%, hypercalcemia (serum calcium ≥11 mg/dl) in 23% and lytic bone disease in 74% of pts. Compared to pts ≥50 years, young pts presented less often with moderate/severe RI (p<0.001) or anemia (p=0.029), more often with lytic bone disease (p<0.001) but there was no difference in the frequency of hypercalcemia or thrombocytopenia (p>0.3 for both). High risk cytogenetics were present in 15% (vs 10% in the older pts, p=0.003) but elevated LDH was similar in frequency between groups. According to ISS, 43%, 24% and 33% were stage 1, 2 & 3 respectively, per R-ISS (N=247 pts) 28%, 59% and 13% for were R-ISS-1, -2 & -3 and by R2-ISS (in N=178 pts), 25% were low, 26% low-int, 30% int-high and 19% high risk respectively. Stage distributions were significantly different than in older pts (p<0.01 for all). First-line was based on bortezomib (+/- chemotherapy) in 48.5%, IMiDs in 14%, PI+IMiDs in 25%, in 5% was daratumumab-based; response rate to induction was 89% and 73% received ASCT as part of 1st line therapy. Non transplanted patients had more often severe RI (23% vs 12%), lytic bone disease (91% vs 56%), high risk cytogenetics (23% vs 12%), failure to achieve at least PR (17% vs 1%) and were diagnosed after 2015. After a median follow up of 55 months, 5-year OS rate was 76%, projected OS at 10 years is 64% and estimated median OS exceeds 15 years. The 5- & 10-year OS for R-ISS-1 was 87% & 73%, for R-ISS-2 was 70% & 62% and for R-ISS-3 was 61% & 16% respectively. Compared to pts 50-65 years, 5 year-OS was 76% vs 71% and 10 year OS was 64% vs 51% (p=0.013) (Fig.1). ISS, R-ISS and R2-ISS were significant prognosticators of OS (p<0.001 for all). Depth of response to induction (CR or better) was associated with better OS (there was no difference for pts with VGPR vs PR). There was no significant difference in terms of OS according to the type of primary therapy but ASCT was the most important factor for better OS in univariate and multivariate analysis (HR:0.412, p<0.001). Although the follow-up of the recently diagnosed pts is shorter, there was no significant improvement in the OS of pts diagnosed after 2015 (vs before) or of those diagnosed after 2010 (vs before). In contrast, among pts aged 50-65 there was a significant OS improvement after 2010 (vs before) and a significant trend after 2015 (vs before). Summary/Conclusion: young pts (<50 years of age) with MM present with different characteristics than older pts and lower risk disease; their median OS is long but substantially shorter than of the non-affected population of similar age. Our data indicate that ASCT is a critical treatment for these pts and should not be omitted even when newer therapies are available.Keywords: Myeloma, Multiple myeloma