The role of allogeneic transplant for adult Ph+ ALL in CR1 with complete molecular remission: a retrospective analysis

• Published in: Blood Vol. 140; no. 20; pp. 2101 - 2112
• Main Authors: Ghobadi, Armin, Slade, Michael, Kantarjian, Hagop, Alvarenga, Julio, Aldoss, Ibrahim, Mohammed, Kahee A., Jabbour, Elias, Faramand, Rawan, Shah, Bijal, Locke, Frederick, Fingrut, Warren, Park, Jae H., Short, Nicholas J., Gao, Feng, Uy, Geoffrey L., Westervelt, Peter, DiPersio, John F., Champlin, Richard E., Al Malki, Monzr M., Ravandi, Farhad, Kebriaei, Partow
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17-11-2022
• Subjects: Acute Disease; Adult; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Complement 3b; Recurrence; Remission Induction; Retrospective Studies; Transplantation, Homologous
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2022016194

•In Ph+ ALL, allogeneic transplant in first remission does not improve survival for patients achieving a deep molecular remission.•The use of transplant was associated with lower incidence of disease relapse but increased treatment-related mortality.
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Historically, Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has been associated with poor outcomes, and allogeneic hematopoietic cell transplantation (allo-HCT) is recommended in first complete remission (CR1). However, in the tyrosine kinase inhibitor (TKI) era, rapid attainment of a complete molecular remission (CMR) is associated with excellent outcomes without allo-HCT, suggesting transplant may not be required for these patients. To test this hypothesis, we retrospectively identified adult patients with Ph+ ALL treated with induction therapy, including TKIs, and attained CMR within 90 days of diagnosis at 5 transplant centers in the United States. We compared outcomes of those who did and did not receive allo-HCT in first remission. We identified 230 patients (allo-HCT: 98; non-HCT: 132). The allo-HCT cohort was younger with better performance status. On multivariable analysis (MVA), allo-HCT was not associated with improved overall survival (adjusted hazard ratio [aHR]: 1.05; 95% CI, 0.63-1.73) or relapse-free survival (aHR: 0.86; 95% CI, 0.54-1.37) compared with non-HCT treatment. Allo-HCT was associated with a lower cumulative incidence of relapse (aHR: 0.32; 95% CI, 0.17-0.62) but higher non-relapse mortality (aHR: 2.59; 95% CI, 1.37-4.89). Propensity score matching analysis confirmed results of MVA. Comparison of reduced-intensity HCT to non-HCT showed no statistically significant difference in any of the above endpoints. In conclusion, adult patients with Ph+ ALL who achieved CMR within 90 days of starting treatment did not derive a survival benefit from allo-HCT in CR1 in this retrospective study.
Regimens combining intensive chemotherapy with tyrosine kinase inhibitors have improved outcomes for adults with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). In this month’s CME article, a retrospective analysis incorporating propensity matching, Ghobadi and colleagues find that in patients achieving complete molecular remission by 90 days, elective allogeneic transplant in first remission reduces the risk of relapse at the expense of transplant-related morbidity and mortality, providing no survival benefit. These data argue for reserving allogeneic transplant for salvage in such patients.