A Parametric Analysis of Overall Survival (OS) in Patients with Relapsed/Refractory (R/R) B-cell Acute Lymphoblastic Leukemia (ALL) Who Have Received Hematopoietic Stem Cell Transplant (HSCT)
Author(s)
Russell-Smith TA1, Chadda S2, Le Reun C3, Doogan E2, Bajko P2
1Pfizer Inc, New York City, NY, USA, 2Genesis Research, Newcastle upon Tyne, UK, 3Independent, Sainte-Anne, GP, France
OBJECTIVES: Identify studies with R/R B-cell ALL patients with who have undergone HSCT that report OS and conduct analysis to determine long-term survival. METHODS: An SLR was conducted to identify studies with survival data in R/R B-cell ALL patients that had undergone HSCT. Of 25 studies identified, nine had Kaplan-Meier and one had patient-level OS data. Individual patient data was recreated from digitized Kaplan-Meier curves using the Guyot algorithm. A single curve was produced from pooled data. Six parametric models were tested (exponential, Weibull, Gompertz, lognormal, loglogistic and Generalized Gamma) considering: Akaike information criteria (AIC), curve fit, and plausibility of longer-term extrapolation. Subgroup analysis was conducted using four studies which measured OS from time of HSCT and was compared to global analysis which also included studies whose baseline point fell either side of HSCT. RESULTS: OS data was available for 503 patients, with a median OS of 11.4 months. A sharp drop in survival was observed during year one, followed by a slower decline and a plateau at 24.4% survival after 4 years. 5-year survival probability was 24.4% (95% CI, 20.5-28.5%) and 28.4% (95% CI, 22.1-34.9%) for global and subgroup analysis, respectively. The Generalized Gamma and Gompertz parametric models both fit the criteria for longer-term extrapolation. The Generalized Gamma model predicted OS at 10.4% versus 14.8% at 15 years, 8.3% versus 12.8% at 20 years, and 6.9% versus 11.4% at 25 years for global and subgroup analysis, respectively. The Gompertz model predicted long-term OS to plateau indefinitely at 23% versus 25.6% just prior to the 10-year mark in the global and subgroup analysis, respectively. CONCLUSIONS: This analysis synthesizes existing OS data and predicts future survival of R/R B-cell ALL patients, filling a clinical evidence gap and providing models usable for economic evaluations. Survival appears significantly more stable past 4 years.
Conference/Value in Health Info
2021-05, ISPOR 2021, Montreal, Canada
Value in Health, Volume 24, Issue 5, S1 (May 2021)
Code
PSU17
Topic
Clinical Outcomes, Methodological & Statistical Research
Topic Subcategory
Relating Intermediate to Long-term Outcomes
Disease
Oncology, Rare and Orphan Diseases, Surgery, Systemic Disorders/Conditions