Restoring Functional Deficits in Older Adults with Hematologic Malignancy
Authors: Rosko Ashley E. , Wall Sarah A , Baiocchi Robert A , Benson Don M. , Brammer Jonathan E. , Byrd John C. , Efebera Yvonne A. , Maddocks Kami J. , Rogers Kerry A. , Presley Carolyn , Jones Desiree , Huang Ying , Naughton Michelle 
Published: November 2019

Background: Geriatric deficits in patients with malignancy are predictive of morbidity and mortality. Measuring geriatric deficits provides additional prognostic information not otherwise captured in routine oncology care. Currently, the gap in geriatric-care delivery is the paucity of data demonstrating effective interventions once geriatric deficits are identified. Older adults with hematologic malignancy are understudied and evaluating both the impact of geriatric factors and interventions to improve upon geriatric deficits are warranted. Here we demonstrate the impact of identifying functional impairment and an exercise program among older adults with hematologic malignancy.
Methods: This was a single center prospective study of older patients (≥60 years) with hematologic malignancy. Patients actively receiving any therapeutic treatment (chemotherapy, immunotherapy, targeted agents) were enrolled in a six-month exercise program to attenuate functional decline. The Otago Exercise Program (OEP) has been found to be an effective exercise regimen to improve functional balance, muscle strength, and prevent fall-related injury and mortality.1 The OEP is a structured combination of physical therapist prescribed individualized exercise plans with home-based exercise targeted to improve balance and functional decline. Patients enrolled had mild or moderate impairments in physical function, as defined by a score ≤9 on the Short Physical Performance Battery (SPPB). Patients were evaluated at baseline for geriatric deficits (Visit 1), after four months of OEP training (Visit 2), and following two months of self-directed exercise (Visit 3 - end of study) using a standardized Geriatric Assessmpent (GA) tool (CARG GA). The relationship between geriatric deficits and mortality and hospital utilization were analyzed. The change in GA factors over 3 visits were evaluated through a linear mixed model. The proportional hazards model was built to assess the association between Visit 1 GA and overall survival (OS), where OS was defined as time from date of V1 to death, censoring patients who were still alive at time of last follow-up. The generalized linear models were used to link Visit 1 GA with other clinical outcomes such as hospital length of stay (LOS) and the probability of emergency room (ER) visit.
Results: Older adults (median age: 75.5; range 62-83) actively receiving chemotherapy for hematologic malignancy were enrolled (n=30). Physical health scores as measured by the MOS-PFS increased significantly at the second visit. [Median MOS-PFS: V1=55 (0-100); V2=70 (30-100), p<.01; V3=57.5 (0-90), p=0.43], where patient reported KPS increased significantly and the improvement was sustainable [Median KPS: V1=80 (40-100); V2=90 (60-100), p=0.02; V3=90 (50-100), p=0.04]. Objective measures of physical function improved to normal scores by visit 2 and were sustained [Median SPPB: V1=7 (0-11); V2=11 (2-12), p<.01; V3=9 (2-12), p<0.01]. With a median follow-up of 21.4 months, 9 patients had died. Half of patients were hospitalized either once or multiple times with a median of 3 admissions (range 1-7).The total LOS ranged from 2 to 41 days with a median of 13 days. During the study period and 1-year follow up, 67% (20/30) patients had ER visits with a median count of 1.5 visits (range 1-6). The SPPB was the only tool that was associated with all three clinical outcomes; OS with a hazard ratio (HR) of 0.80 (95% confidence interval (CI) 0.65-0.97, p=0.03), LOS [Incidence Rate Ratio=0.86 (95% CI 0.75-0.98), p=0.02], and the odds of ER visit [odds ratio = 0.77 (95% CI 0.62-0.94), p=0.01]. Chronologic age had no relationship with OS, LOS, or ER utilization.
Conclusions: Functional deficits of older patients with hematologic malignancy on active chemotherapy, both subjective and objective metrics, improved with the OEP exercise program. Objective markers of physical function (SPPB) correlated with mortality and hospital utilizations among this population. There was no significant relationship between age and clinical outcomes. Mitigating functional impairment among older adults with hematologic malignancy is important to improve clinical outcomes in this high-risk population.

Disclosures
Rosko: Vyxeos: Other: Travel support. Baiocchi:Prelude: Consultancy. Brammer:Celgene: Research Funding; Seatlle Genetics: Honoraria, Speakers Bureau. Byrd:Novartis: Other: Travel Expenses, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Acerta: Research Funding; Ohio State University: Patents & Royalties: OSU-2S; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Research Funding; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau. Efebera:Takeda: Honoraria; Akcea: Other: Advisory board, Speakers Bureau; Janssen: Speakers Bureau. Maddocks:Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Merck: Research Funding; Teva: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding. Rogers:Acerta Pharma: Consultancy; AbbVie: Research Funding; Genentech: Research Funding; Janssen: Research Funding.