Clinicians' Perspectives on Cure in Adult Patients with Acute Lymphoblastic Leukemia with Minimal Residual Disease: A Delphi Study

Hematologic complete remission (CR) is achievable for most adults with B cell precursor acute lymphoblastic leukemia (BCP-ALL). However, minimal residual disease (MRD) in patients with hematologic CR is associated with increased risk of relapse, shorter survival, and poorer transplantation outcomes. This study explored the concept of cure in adults with Philadelphia chromosome-negative (Ph-) BCP-ALL by MRD status at first hematologic CR (CR1) to inform evaluation of the clinical and economic benefits of new agents, where the concept of cure is important but long-term data are not available. The study used modified Delphi methodology involving clinicians experienced in the treatment of adult ALL. Participants completed a questionnaire, which was followed by country-specific panel discussions to discuss results and identify consensus on concepts and definitions. Clinicians from France (n = 4), Germany (n = 4), and the UK (n = 5) took part. Participants described cure in terms of the probability of future relapse. Relapse-free survival (RFS) was the preferred outcome measure to describe cure for the three patient groups considered (patients with MRD at CR1; patients who become negative for MRD after further treatment; patients who continue to have MRD). Consensus was reached on definitions of cure: that cure would begin to be considered at 3 years' RFS and/or would be highly likely at 5 years' RFS. Participants agreed that patients with MRD should usually undergo hematopoietic stem cell transplantation to have the best chance of survival; consensus was reached that alternatives are required when transplantation is not an option. Panels agreed that patients who achieve cure have a higher mortality rate and lower health-related quality of life than the general population. This study provides quantitative and qualitative information on the concept of cure in Ph- BCP-ALL in CR by MRD status applicable to interpreting the value of new therapies.Funding: Amgen.Plain Language Summary: Plain language summary available for this article.