(PA-425) Enhancing GAH Score to Optimize Tolerance to Quadruplet Therapies in Multiple Myeloma: A Subanalysis of the GEM2017FIT Trial

The Geriatric Assessment in Hematology (GAH) scale, using a 42-point threshold, predicts treatment-related toxicity in hematologic neoplasms and helps guide frailty-adapted therapy. In the GEM2017FIT trial, transplant-ineligible multiple myeloma (MM) patients with GAH score of ≤42, received 18 induction cycles of either VMP/Rd (control), DKRd, or KRd (experimental). DKRd and KRd showed higher minimal residual disease negative after induction compared with VMP/Rd, meeting the primary endpoint. However, DKRd was associated with higher toxicity and toxicity-related mortality, particularly in patients with GAH >20. In contrast, KRd was better tolerated across all GAH scores. This finding raised the question of whether optimizing the GAH score could improve quadruplet tolerability and allow more patients to receive them. This analysis focused on the DKRd and KRd arms.

Methods:

We conducted a post hoc analysis of patients treated with DKRd or KRd in the GEM2017FIT trial. Patients were stratified as fit (GAH >20) or ultra-fit (GAH < 20). We analyzed GAH components contributing to fitness classification and assessed their modifiability

Results:

Of 307 patients (153 DKRd, 154 KRd), 151 (49.3%) were fit and 155 (50.7%) ultra-fit, and were balanced across arms (DKRd: 75 fit, and 78 ultra-fit; and KRd: 77 fit, and 77 ultra-fit). No baseline differences were observed between groups. The main contributors to being classified as fit were abnormal mini nutritional assessment short form (MNA-SF, 48.7%) and any dependence on activities of daily living (ADL, 46.7%). Other GAH components (polypharmacy, gait speed, mental and physiological status, comorbidities) did not significantly differ. In the DKRd arm, fit patients more often had abnormal MNA-SF (47.3% vs. 0.0%, P< 0.001) and ADL dependence (51.4% vs. 0.0%; P< 0.001) as compared with ultra-fit patients. KRd arm showed similar results (abnormal MNA-SF: 49.4% vs. 0.0%, P< 0.001; ADL dependence: 44.2% vs. 0.0%, P< 0.001). Notably, certain items of MNA-SF and ADL dependence (GAH score: 40 and 22 points, respectively) are potentially modifiable, offering an opportunity to optimize the overall GAH score. With target interventions, 75/151 fit patients (49.7%) could become ultra-fit: 42/75 (56.0%) in the DKRd arm and 33/77 (42.9%) in the KRd arm. Nutritional improvement could reclassify 47/151 fit patients (31.1%, 26 in DKRd and 21 in KRd), while ADL-focused physical interventions could benefit 28/151 fit patients (18.6%, 16 in DKRd and 12 in KRd).

Conclusions:

Nutritional status and ADL dependence were the key GAH domains driving fitness classification in MM patients treated with DKRd or KRd. Both are potentially modifiable and, if addressed, could reclassify nearly half of fit patients as ultra-fit, thereby optimizing their ability to tolerate and benefit from quadruplet therapies. A multidisciplinary approach is essential to target these domains, improving treatment eligibility and outcomes in older patients