The Lynx Group

Fludarabine-Busulfan Conditioning Demonstrates Improved Outcomes in Patients with Myelofibrosis After Allo-HSCT

Conference Correspondent

Although several drugs have been approved or are currently under investigation for the management of myelofibrosis (MF), the only curative therapy remains allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Conditioning regimens for allo-HSCT includes either myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC), but the optimal details for each of these approaches have not been determined. The current study evaluated patient outcomes undergoing conditioning regimens in MAC (fludarabine/busulfan [FLU/BU] vs busulfan/cyclophosphamide [BU/CY]) or in RIC (FLU/BU vs fludarabine/melphalan [FLU/MEL]). In the RIC setting, melphalan may be dosed at 100 mg/m2 or 140 mg/m2.

This study enrolled 872 patients aged ≥18 years with MF who underwent allo-HSCT. In 379 patients, MAC was used (FLU/BU, n = 247; BU/CY, n = 132) while 493 patients underwent RIC (FLU/BU, n = 166; FLU/MEL, n = 327). Overall survival, disease-free survival, non-relapse mortality, relapse, acute and chronic graft-versus-host disease (GVHD), and GVHD-free relapse-free survival (GRFS) were evaluated.

Significant differences in outcomes were observed within both the MAC and RIC settings based on the conditioning regimen. In the MAC setting, BU/CY was associated with a higher risk of grade 2-4 (hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.67-3.25, P <.01) and grade 3-4 (HR, 2.31; 95% CI, 1.52-3.52; P <.01) acute GVHD as well as inferior GRFS (HR, 1.94; 95% CI, 1.49-2.53; P <.01) compared with FLU/BU. In the RIC setting, FLU/MEL was associated with inferior overall survival (HR, 1.80; 95% CI, 1.15-2.81; P <.01), higher risk of non-relapse mortality (HR = 1.81; 95% CI, 1.12-2.91, P = .01), and acute GVHD (grade 2-4: HR, 1.45; 95% CI, 1.03-2.03; P = .03 and grade 3-4: HR, 2.21; 95% CI, 1.28-3.83; P <.01) compared with FLU/BU. Higher risks associated with FLU/MEL were primarily observed early after transplant at both doses (100 mg/m2 or 140 mg/m2).

In conclusion, in patients with MF who undergo allo-HSCT, FLU/BU conditioning regimens may accord better outcomes in both the MAC and RIC settings. Taken together, this type of patient may experience variable outcomes depending on the specific conditioning regimen, and modifications should be taken into consideration in patients undergoing allotransplant.

Source: Guru Murthy GS, Kim S, Estrada-Me N, et al. Superior outcomes with fludarabine-busulfan (Flu/Bu) based conditioning for allogeneic hematopoietic cell transplantation in myelofibrosis - a comparative analysis by CIBMTR. American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021. Abstract 912.

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