Patient-Reported Outcomes of BMT CTN 1703: A Randomized Phase III Study for Gvhd Prophylaxis - a Quality of Life Evaluation

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.897-897
• Main Authors: Holtan, Shernan G., Martens, Michael J, Al Malki, Monzr M., Efebera, Yvonne, Kitko, Carrie L., Reshef, Ran, Rezvani, Andrew R., Shaffer, Brian C., Solh, Melhem M., Yao, Janny M., Runaas, Lyndsey, Elmariah, Hany, Larkin, Karilyn T., El Jurdi, Najla H, Gooptu, Mahasweta, Loren, Alison W, Hall, Aric C., Alousi, Amin, Jamy, Omer, Clark, William, Kean, Leslie, Bhatt, Ami S., Perales, Miguel-Angel, Applegate, Kristy, WU, Juan, Liefer, Eric, DiFronzo, Nancy, Jones, Richard J., Horowitz, Mary M., Mattila, Deborah, Hamadani, Mehdi, Bolanos-Meade, Javier
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-187859

Introduction A randomized phase III trial of post-transplantation cyclophosphamide (PTCy), tacrolimus, (Tac), and mycophenolate mofetil (MMF) versus tacrolimus/methotrexate (Tac/MTX) for graft-versus-host disease (GVHD) prophylaxis showed superior graft-versus-host disease-free, relapse-free survival (GRFS) in the PTCy-containing arm (NEJM, 2023). Here, we report the effect of GVHD prophylaxis on patient-reported outcomes and impact on quality of life (QOL). Methods The QOL study component of BMT CTN 1703 employed four primary endpoints: Lee Chronic GVHD Symptom Score and the PROMIS subscales of physical function, gastrointestinal symptoms, and satisfaction with participation in social roles. Secondary endpoints included hemorrhagic cystitis symptoms and Lee symptom subscale differences, with questionnaires to English and Spanish-speaking participants at enrollment and on Days 100, 180, and 365 post-transplant. Given the risk of missing assessments, an inverse probability weighted-independent estimating equations (IPW-IEE) model was applied for score comparison between arms, adjusting for baseline score, assessment time, age, donor type, disease risk index (DRI), planned conditioning regimen, and planned use of post-transplant maintenance therapy. Significance was declared at a 1.25% level for score comparisons between arms after Bonferroni correction for multiple testing. The analysis approach classified patients according to the intention-to-treat principle. Results QOL survey completion rates for patients at each timepoint were similar, exceeding 70% in each study arm. With the Lee Chronic GVHD Symptom Scale, higher scores indicate more severe symptoms. The IPW-IEE models indicated that the Lee Chronic GVHD Symptom Scale total scores were significantly lower in the PTCy arm compared to Tac/MTX at day 100 (mean difference [MD] -2.22, 99% confidence interval [CI] -5.05 to 0.61) and day 365 (MD -1.84, 99% CI -5.13 to 1.45, p=0.01 for overall treatment effect across all timepoints, Figure 1). Nutrition subscores were significantly better with PTCy at day 100 (MD -2.41, 99% CI -5.06 to 0.24, p=0.0014). Mouth scores were significantly better in the PTCy arm at day 365 (MD -7.09, 99% CI -13.21 to -0.98, p=0.0035). Patients over 65 years of age had better psychological subscores across the study population (MD -4.80, 99% CI -8.91 to -0.69, p=0.0026); no interaction was found between age and study treatment. Patient-reported hemorrhagic cystitis symptoms showed