Self-reported geriatric impairments and treatment toxicity in older patients with multiple myeloma - a single center prospective study

Abstract Introduction: Multiple myeloma (MM) predominantly affects older adults who vary widely in physiological status and treatment outcomes. Comprehensive Geriatric Assessment (CGA) is considered the gold standard for frailty assessment in older cancer patients (pts), but clinical useis limited. Current frailty tools for MM include only select GCA domains, rely on trial datasets, and do not incorporate pt-reported outcomes (PROs). Since their development, treatment strategies have evolved with the use of anti-CD38 MAbs and quadruplets in older pts. The impact of geriatric impairments on treatment tolerance in the era of modern therapy remains unclear and changes in geriatric domains during treatment are not well characterized. Aim: This prospective study evaluates the association between pt-reported CGA and treatment outcomes in older MM pts.Methods: We included MM pts ≥60 years initiating a new treatment at Mayo Clinic from March 2023-June 2024. Pts completed the CARG GCA (Hurria et al 2005) electronically prior to and after 4 treatment cycles. We collected data on toxicity using CTCAE and PRO-CTCAE and quality of life using the PROMIS10-GH SF.Results: Ninety pts were enrolled. Median age was 72 (range: 63-86), 42% female, and >90% non-Hispanic white. Over half (59%) were newly diagnosed with 41% and 56% receiving quadruplets and triplets, respectively. Among newly diagnosed pts, 34% had early stem cell transplant. Baseline median self- and physician- reported KPS were 80% and 90%, respectively, with high correlation (r=0.657). The median number of meds per pt was 9 (range:0-30), 39% had ≥3 comorbidities, 21% reported ≥1 fall in the past 6 months, and 40% reported ≥1 IADL limitation. On the Hospital Anxiety and Depression Scale, 3% and 7% had anxiety and depression, respectively. On the Blessed Orientation-Memory-Concentration test, 19% had mild cognitive impairment, and 1% had severe cognitive impairment. While only 19% had grade (G) ≥3 non-hematologic toxicity by CTCAE, 71% had ≥1 treatment delay, dose reduction, or discontinuation, and 39% had ≥1 ED visit or unplanned hospitalization within the first 4 cycles. This suggests physician grading of non-hem toxicities may inadequately capture toxicity burden from MM therapy. Notably, the rate of G≥3 toxicity by PRO-CTCAE was 49%, highlighting the discrepancy between physician- and pt-reported symptom burden. CGA domains significantly associated with G≥3 non-hem toxicity were: age (74 v 71.5, p=0.032), ≥3 comorbidities (65% v 33%, p=0.015), anxiety (18% v 0%, p=0.006), ≥1 IADL limitation (65% v 33%, p=0.018), physician KPS ≤80 (53% v 27%, p=0.042), limitations in vigorous activities (100% v 78%, p=0.023) and limitations in climbing several flights of stairs (88% v 56%, p<0.001). Predictors of PRO-CTCAE G≥3 toxicity were ≥1 falls (30% v 11%, p=0.030), ≥3 comorbidities (52% v 26%, p=0.011), polypharmacy (≥9 meds) (67% v 43%, p=0.023), and physician KPS ≤80 (43% v 22%, p=0.030). CGA domains associated with ≥1 treatment adjustments were polypharmacy (62% v 33%, p=0.017) and unintentional weight loss (35% v 12%, p=0.028). Polypharmacy was the only domain associated with healthcare utilization (68% v 45%, p = 0.040), which may reflect underlying multimorbidity and greater pain burden. On multivariable logistic regression, any level of limitation in climbing several flights of stairs (OR: 6.0, 95% CI 1.2-30.3; p= 0.030) and older age (OR: 1.1, 95% CI 1.0-1.1; p=0.032) were independently associated with G≥3 non-hem toxicity, reflecting impaired functional status and reduced physiologic reserve, while ≥3 comorbidities only trended toward significance (OR:1.9, 95% CI 1.1-3.9, p=0.051).Compared to baseline, there were no significant changes in CGA domains or PROMIS10 scores after 4 cycles. While there was no significant difference in the proportion of pts reporting limitations in IADLs or physical function, we observed heterogeneity among individual pts, with changes in all 3 directions (improvement, stability, and decline). Conclusions: Geriatric impairments are prevalent in older pts with MM; pt-reported impairments are significantly associated with G≥3 non-hem toxicities, need for treatment modifications, and increased healthcare utilization, even in the era of novel therapies. Physical functional trajectories during treatment are variable among individual pts, underscoring the need for personalized treatment strategies and reassessment of geriatric domains throughout treatment.