Clinical Outcomes in Elderly Patients Treated Outside Clinical Studies: Highlighting the Octogenarian Experience

• Triplets provide longer TTNT and improved OS than doublets in Octogenarians.

• The introduction of daratumumab-based regimens resulted in significantlylonger TTNT.

With an aging population, multiple myeloma (MM) increasingly affects octogenarians (Octo, ≥80 years), but data on their management and outcomes, particularly if treated outside clinical trials, remain limited. This retrospective study analyzed 652 patients aged ≥70 years, diagnosed with active MM between 2014 and 2023, identified in the Maccabi Healthcare Services medical records. Patient characteristics, treatment, time to next treatment (TTNT), overall survival (OS), and factors influencing outcomes, were compared between Octo and elderly (EL) patients aged 70-<80 years. The results show that Octo patients (median age 83 years) had more comorbidities (mean 3 vs. 2) and higher Charlson comorbidity scores than EL (≥6, 53% vs. 23%, p<0.001), leading to lower rates of anti-MM therapy administration (83% vs. 96%, p<0.001) and reduced triplet/quadruplet (n=87/5) use (38.8% vs. 55%, p=0.02). Over a median follow-up of 25 months (0.1-124), Octo patients had significantly shorter median OS; 25.9 vs. 71.3 months, (p<0.001), and 33 vs. 76.9 months among treated patients only (p<0.001). TTNT was similar (17.8 vs. 22.1 months, p=0.43). Multivariate analysis showed triplet/quadruplet to be associated with improved TTNT (HR 0.61, p<0.001) and OS (HR 0.63, p<0.001) compared to doublets, while higher Charlson scores and age ≥80 years predicted worse OS (HR 1.5, p=0.003, HR 2.27, p<0.001). Daratumumab-based therapies enhanced TTNT in both age groups (HR 0.54, p=0.017). In conclusion, higher comorbidities in Octo patients adversely affected their management and survival. However, daratumumab positively influenced outcomes, underscoring the need for tailored approaches to optimize treatment in older MM patients.