Impact of pre-transplant functional status and comorbidities on outcomes in individuals with multiple myeloma undergoing autologous hematopoietic cell transplantation

Abstract

Abstract Background: Multiple myeloma (MM) is a hematologic malignancy for which autologous hematopoietic cell transplantation (auto-HCT) in eligible patients after induction therapy remains the standard of care. However, response and tolerability to transplant is variable, and understanding factors such as pre-HCT functional status, as well as their impact on successful post-transplant outcomes, is an important consideration. We hypothesized that pre-transplant functional status and comorbidities before auto-HCT in MM patients would impact survival outcomes, hospital length of stay (LOS), and treatment response. Methods: This retrospective cohort study included MM patients who underwent auto-HCT between 01/2010-07/2021. Data on baseline demographics, HCT-CI, pre-HCT physical therapy evaluations (including heart rate, pain score, 30 second sit to stand, single-leg balance, recent falls, strength of upper/lower extremities, timed get up and go, 6 minute walk test, subjective sensation changes reported by patients, coordination tested by finger-to-nose testing, and endurance evaluated subjectively by the physical therapist administering the evaluation) were collected and analyzed. Outcomes included overall survival (OS), progression free survival (PFS), best response (very good partial response (VGPR)/complete response (CR) vs others), and LOS post-HCT. Univariate and multivariate Cox regression models assessed OS and PFS. Logistic regression was used to evaluate LOS. P<0.05 was set for statistical significance. Results: We analyzed a total of 456 consecutive auto-HCT patients at a single center. Median age was 62 years (range: 28-81), 52% of individuals were male, and 87% were Non-Hispanic White. Most patients (65%) achieved a vVGPR or better. At 5-years post-auto-HCT, 23% of patients died with disease as the most common cause of death (87%) followed by infections (11%) and second cancers (9%). Pre-HCT physical therapy assessments showed 83% of patients did not require assistive devices, and 96% were independent in activities of daily living. Majority of individuals had normal coordination (92%) and endurance (84%). Sensation was diminished in 58% of individuals and 65% of individuals self-reported pain. Recent falls were reported in 9%. Lower extremity strength was normal in 83% of individuals and 88% had normal upper extremity strength. Weight bearing was normal in 85% (left leg) and 86% (right leg). Among those tested, 74% of individuals balanced ≥6 seconds on the left leg and 72% on the right leg, and 95% performed ≥25 step-ups on the left leg and 96% on the right, 62% performed >10 sit to stands in 30 seconds, 50% achieved ≥376 meters on the 6-minute walk test, and 80% of patients had a heart rate recovery within 5 minutes. Median follow-up in survivors is 5.8 years. Patients unable to perform at least 10 sit-to-stands had 47% higher risk of 5-year mortality [HR=1.47,95% CI=1.00-2.18; P=0.05] compared to patients who could perform greater than 10 sit-to-stands adjusting for age, sex, melphalan conditioning <200 mg/m2, not in CR at time of auto-HCT, pulmonary comorbidity, and psychological comorbidity. No physical function measures were associated with PFS. Median LOS from infusion of autoHCT to discharge was 18 days (range 9-84 days). Patients unable to balance on their right lower leg for at least 6 seconds had higher odds of longer LOS (≥18 days95% CI=1.54-4.33; P=0.0003), adjusting for age at auto–HCT, sex, year of auto-HCT, endurance, and upper extremity strength.Conclusion: Pre transplant physical function, in particular inability to balance on the right leg for at least 6 seconds showed significantly higher LOS and <10 sit-to-stands was a significant predictor of poor OS. These findings highlight the potential of pre-transplant functional assessment to optimize objective risk stratification for patients prior to transplant.