Living the recovery: One-year qol outcomes for patients receiving ptcy gvhd prophylaxis on the access clinical trial

Abstract Background: The ACCESS trial (NCT04904588) was designed to evaluate the safety and efficacy of using peripheral blood stem cells from mismatched unrelated donors (MMUD) with post-transplantation cyclophosphamide based graft-versus-host disease (GVHD) prophylaxis. This prospective, phase 2, non-randomized, multicenter trial enrolled patients with high-risk hematologic malignancies who lacked HLA matched donors, many of whom were from racially/ethnically diverse and socioeconomically vulnerable backgrounds. Primary endpoint results have been previously published, showing 1-year OS and GRFS of 83% (95%CI 73.1 to 90.4%) and 47.6% for MAC and 78.6 (95%CI 67% to 86.5%) and 50.8% for RIC/NMA, respectively. Here we describe the quality of life (QOL) and financial well-being of patients in the first year post-HCT and compare this in patients with mild/none versus moderate/severe chronic-GVHD (cGVHD). Methods: This longitudinal study included patients enrolled in the ACCESS trial who completed at least one PRO at any timepoint for descriptive statistics and those who completed both a baseline and a 1-year survey for the univariate analysis. Patients completed surveys about their QOL pre-transplant (baseline), 100 days post-transplant (D100), D180, and 1 year after HCT. For the primary QOL endpoint, Lee Symptoms Scale (LSS) was assessed 1-year post-HCT comparing patients who developed mild/no or mod/sev cGVHD. LSS is a 30-item validated measure of cGVHD symptoms and includes an overall score (0-100) where higher values indicate more symptom burden. PRO Measurement Information System (PROMIS) measure for physical function and fatigue were used to identify physical and social well-being. Financial toxicity was assessed using the 12-item COmprehensive Score for financial Toxicity (COST) measure capturing material and psychosocial financial hardship (score 0-44, higher scores indicating better financial well-being). Analysis of covariance was conducted to compare the 1-year PRO score between patients with moderate/severe vs none/mild cGVHD (reported any time by the 1-year timepoint), adjusting for baseline scores. Statistical significance was considered to be p<.05. Clinically meaningful differences were defined as >5 points for LSS and PROMIS measures. Results: Among the 268 patients enrolled into the ACCESS trial, 203 (76%) submitted PRO data at baseline. 232 (87%) submitted at least one survey. Patients were a median age of 50 (range 20-65) among MAC recipients and 65 (range 22-78) among RIC/NMA conditioning recipients. 63% of MAC patients were male compared to 48% male among RIC/NMA recipients. 43% of MAC patients and 53% of RIC/NMA had AML. 37% of MAC patients had a household income of less than $80,000 compared to 40% of RIC/NMA patients. At baseline, 18.2% of patients reported moderate or severe financial toxicity compared to 15.6% at 1-year. At 1-year post-HCT, the mean LSS overall score was 11.0 (range 0-39.2) which showed a return to baseline values (10.8). Similarly, mean fatigue (49.4) and physical function (44.6) average scores at 1-year post-HCT returned to or exceeded baseline levels (49.0, 46.8, respectively). In the analysis population, 95 had no/mild cGVHD and 18 had moderate/severe cGVHD. There was a statistically significant, and clinically meaningful, difference in LSS overall scores between cGVHD groups, controlling for baseline (10.1 v. 15.4; p < .01). Subscale scores were significantly worse in patients with mod/sev cGVHD for skin (17.6 v 8.9; p<.01) and energy (30.9 v. 20.7; p<.01) at 1-year post-HCT. Likewise, physical function was significantly worse among those with mod/sev cGVHD compared to no/mild (47.6 v 43.1.; p<.05). PROMIS measure scores also suggested clinically meaningful higher fatigue at 1-year for those patients with mod/sev cGVHD (53.5) compared to no/mild cGVHD (49.0), though all within normal limits. Social well-being and financial well-being did not differ significantly by cGVHD groups. Conclusions: These results show QOL for patients is generally similar to general population norms at 1-year post-MMUD HCT (except for mild persistent physical function deficits). Rates of cGVHD were low, but PRO results highlight that moderate/severe cGVHD is associated with persistent symptom burden and impaired physical function, at 1-year post-transplant, underscoring the need for targeted supportive care strategies and continued efforts to reduce the incidence and severity of GVHD.