Treatment Journey of Octogenarian Patients Outside Clinical Trials
Authors: Shpitzer Dor , Cohen Yael C. , Shragai Tamir , Melamed Guy , Reiner-Benaim Anat , Avivi Mazza Irit 
Published: December 2024

Introduction
The proportion of octogenarian (Octo) multiple myeloma (MM) patients (pts) in prospective studies is small and pts included are often fitter than their age group. Data on pts treated outside clinical studies are even scantier. Studies assessing outcomes of Octo pts reported median overall survival (OS) of approximately 2 years (yrs) (Britto J, 2023; Cook G, 2019). The current study investigated the characteristics and outcome of MM pts age ≥70&lt;80 yrs (termed Elderly=El) vs ≥80 yrs (Octo), defining treatment approaches and outcomes.
Methods:
A retrospective study, utilizing data extracted from individuals insured in Maccabi Healthcare Services (MHS). Pts aged≥70 yrs who received anti-MM therapy between 2014 and 2023 were reviewed and outcomes of El vs Octo pts were compared. The index date was the date of first therapy. Pts received first line (1L) treatment according to the Israeli health basket: 2014-2018 bortezomib (V)d , 2019-2022 VRd (V-lenalidomide (R))/Vd/Rd, and since 2023 also, Rd/Vd-daratumumab (Dara), termed “treatment periods”. Time to next treatment (TTNT) and OS were analyzed.
Results
A total of 614 pts; median age 77 yrs (70-96), 409 (66.7%) El and 205 (33.3%) Octo were included. Co-morbidities were greater in the Octo group (median of 3 vs 2, p=0.001). Additionally, Octo pts also had higher prevalence of acute renal failure and anemia at diagnosis (p=0.02 and p&lt;0.001). There were no differences in terms of the proportions of El vs Octo pts treated during the different “treatment periods”.
V-based regimens were used in 307 (50%), R-based in 47 (7.7%), RVD in 168 (27.3%) and Dara-based in 92 (15%). Novel agent-based triplets/quadruplets were less commonly used in the Octo cohort [65 (31.5%) vs 176 (43.2%); p=0.008].
After a median follow-up (FU) period of 36 months (m)(range 0-125), 146 (24%) pts were still receiving 1L treatment: 36 (17.5%) in the Octo and 110 (26.9%) of the El cohort (p=0.01). A total of 164 pts (26.7%) received subsequent lines and are still alive: 35 (17%) in the Octo cohort and 129 (31.5%) in the El cohort (p&lt;0.001). Out of the pts who received subsequent lines, 170 (27.7%) died later: 67 (32.3%) in the Octo cohort vs 103 (25.2%) in the El cohort (p=0.06). Additionally, 129 (21%) died before receiving any subsequent lines of therapy: 67 (32.3%) Octo Vs 62 (15.1%) El cohort (p&lt;0.001).
Median TTNT of the entire cohort was 21.4m; 17.7m for the Octo cohort vs 22.3m for the El cohort (p=0.28). Median TTNT was longer in 2019-2022 than earlier (24m Vs 18.1m, p=0.01), but not in the Octo cohort (16m, p=0.5). The median OS for the entire cohort was 54m (95%CI 47.2-63.6), being shorter for the Octo vs the El cohort; 32.1m (95%CI 14-28) vs 74.4m (95%CI 20-27, p&lt;0.001). Comparing the OS between the treatment periods revealed no significant change in median OS in the Octo cohort (34.7m Vs 31.6m, p=0. 64). Multivariate analysis identified age≥80 yrs (HR 2.22, p&lt;0.001), heart failure (HR 2.54, p&lt;0.001), dementia (HR 1.6, p=0.02) and anemia (HR 1.9, p&lt;0.001) to be associated with shorter OS. Novel agent-based triplets were associated with a longer OS (HR 0.6, p&lt;0.001), and a longer TTNT (HR 0.59, p&lt;0.001) compared to doublets.
Restricted analysis, analyzing factors that affected OS of Octo pts only, revealed heart failure (HR 2.32, p&lt;0.006) and anemia (HR 2.2, p&lt;0.001) to be associated with shorter OS. Osteoporosis predicted shorter TTNT (HR 1.59, p=0.023). Novel agent-based triplets were associated with a longer OS (HR 0.52, p=0.005) and a longer TTNT (HR 0.54, p=0.007) compared to doublets. Additionally, the introduction of Dara at the upfront setting was also associated with a lower risk for progression and need for second line treatment (HR 0.52, p=0. 01).
Conclusions
Octo pts exhibited a higher prevalence of co-morbidities and a lower tolerance to intensive treatment regimens compared to their younger counterparts, resulting in shorter treatment durations and lower OS rates. The results underscore the need for tailored treatment strategies for older pts to improve their outcomes.
Notably, a substantial number of these patients would have been excluded from clinical studies, yet the observed OS was nearly 3 years for Octo and 6 years for El patients, highlighting the impressive survival outcomes in these real-world patients, mainly treated in the pre-Dara era.