Characterization and Comparative Outcomes of Younger Multiple Myeloma Patients
Authors: Tufano-Sugarman Andrea , Islam Shahidul , Davies Faith E , Morgan Gareth , Kaminetzky David , Lahoud Oscar B , Braunstein Marc J 
Published: December 2024

Introduction: With a median age at diagnosis of 69, multiple myeloma (MM) tends to impact older individuals. Patients younger than 50 years represent only 10% of diagnoses and are less well characterized. Some studies have suggested that younger MM patients are more likely to present with lytic lesions, express uncommon isotypes, have higher-risk cytogenetics, and have relatively improved survival. We aimed to characterize this understudied population in the modern era, and compare them to an older cohort age 50 or greater.

Methods: Using our institution's data registry to identify all patients meeting IMWG criteria for MM across our cancer center network between 2010 and 2023, patients less than age 50 (cohort A) were compared to controls age 50 or greater (cohort B) using a 2:1 matching strategy based on three grouped demographic variables: gender, year of diagnosis, and race. Demographics, symptoms, lab values at presentation, cytogenetics, and treatment data were collected. Survival was measured as months from diagnosis to last follow-up or death.

Results: We identified 106 patients in cohort A, with a median age of 44 (range 26-49), and 206 matched controls age 50 or greater in cohort B, with a median age of 68 (range 50-92). Male to female ratio was slightly more skewed in cohort B (46 and 54%) compared to cohort A (49 and 51%). The racial breakdown for cohort A was 21.7% white, 34% black, 27% Hispanic, 10% Asian, and 12% other. This was similar in cohort B due to race matching. The most common isotype in both cohorts was IgG (57.6% in A; 48% in B), however 19% of cohort A had light chain-only disease, compared to 16% of cohort B (P&lt;0.05). For cohort A, staging data was available for 87 patients. 51% presented as R-ISS stage 1, 33% stage 2, and 16% stage 3. For cohort B, staging data was available for 136 patients (stage 1-3: 26%, 52%, and 29%). In cohort A 69% had a BMI &gt; 25 (overweight), and 32% had BMI &gt; 30, (obese), compared with cohort B in which BMIs were 69% BMI &gt;25 and 28% BMI &gt;30. With regard to presentation, in cohort A, incidentally found cases, defined as abnormalities on imaging or labs ordered for another reason, represented 7% of cases, whereas 77% had at least one CRAB symptom at diagnosis. Significant differences included: 32% of cohort A presented with significant anemia (hemoglobin &lt;10 g/dL) compared to 39% of cohort B. 16% of cohort A presented with significant renal dysfunction (creatinine &gt;2 mg/dL) compared to 12% of cohort B. 14% of cohort A presented with hypercalcemia compared to 5.3% of cohort B. 69.8% of cohort A had skeletal involvement at presentation, and the corresponding data from cohort B will be presented. Few of the young patients had previously identified MGUS (3%) or smoldering MM (5%). Regarding cytogenetics, 19% had one or more high-risk features in cohort A. Deletions were the most common cytogenetic abnormality (30%), followed by trisomy (21%) and t(11;14) in 21%. The most common frontline treatment for young patients was RVd. 52% and 35% received 3 and 4 drug induction regimens respectively in cohort A. 73% of these patients were referred for autologous transplant, and 50% proceeded. In cohort A, 4 patients were deceased at the time of analysis. Survival for the entire population was 97.8% at a median follow up time of 65.5 months. In the patients who underwent autologous transplant, 59% of patients did not relapse after transplant and the median post-transplant progression-free survival was 57 (44-71) months. Comparative treatment data and survival analyses between cohorts A and B will be presented.

Conclusions: MM patients age &lt;50 were found to be distinct from the known characteristics of the general population. Survival of the younger cohort was higher than what is reported in literature, which may be related to their relatively better fitness and higher likelihood to received quadruplet regimens and/or proceed to autologous transplant. In addition, higher-risk cytogenetics were not higher than expected in the younger patient cohort. Further analyses with comparison to cohort B remain ongoing as survival data are maturing. With improving outcomes using modern anti-myeloma regimens, the differences in outcomes between younger and older MM patients are likely to lessen over time.