The role of allogeneic transplant in adults with Ph+ ALL in complete molecular remission

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has curative potential in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Moreover, the introduction of tyrosine kinase inhibitors (TKIs) has resulted in deep and durable remission with negative measurable residual disease. Although allo-HSCT has improved non-relapse mortality (NRM), it still occurs in a proportion of patients in complete remission, and its role in this setting is widely debated.¹

Here, we summarize a retrospective study published by Nishiwaki et al.¹ in the American Journal of Hematology comparing outcomes of patients with Ph+ ALL in complete molecular remission who received allo-HSCT vs no allo-HSCT in the first CR.

Study methods¹

• This study included adult patients aged 15−64 years with newly-diagnosed Ph+ ALL who achieved complete molecular remission within 3 months of diagnosis.
• Patients were enrolled from three prospective studies (JALSG Ph+ALL202; Ph+ALL208 study; Ph+ALL213 study) conducted by the Japan Adult Leukemia Study Group.
• The key endpoints included the incidence of relapse and NRM, overall survival (OS), relapse-free survival (RFS), and graft-versus-host disease-free survival (GFRS).

Key findings¹

• Of the 147 patients included in the analysis, 101 received allo-HSCT and 46 did not.
• Patients in the allo-HSCT vs the non-allo-HSCT cohort were younger (median age, 53 vs 58 years) and received more dasatinib as first-line TKI (40% vs 17%).

Univariate analysis

• The 5-year survival outcomes were significantly higher in the allo-HSCT vs non-HSCT cohort (OS, 73% vs 41%; p = 0.0004; RFS, 68% vs 30%; p < 0.0001).
• Chromosomal risk and TKI were associated with higher OS and RFS.
• Although the 5-year NRM was similar in both cohorts (17% vs 10%; p = 0.17), the 5-year relapse rate was significantly lower in the allo-HSCT vs non-HSCT cohort (17% vs 60%; p < 0.0001).
• The 5-year GFRS was 51% in the allo-HSCT cohort vs 30% in the non-HSCT cohort (p = 0.01).

Multivariate analysis

• Allo-HSCT was associated with higher OS (adjusted hazard ratio [aHR], 0.54; p = 0.04), RFS (aHR, 0.21; p < 0.001), and GFRS (aHR, 0.43; p = 0.002) compared with non-HSCT (Figure 1).
• White blood cell count, TKI, and chromosomal risk were also associated with higher OS and RFS.
• Allo-HSCT was associated with a lower relapse rate (aHR, 0.10; p < 0.001) but a higher NRM (aHR, 3.49; p = 0.03) compared with the non-HSCT cohort.
• The median time from diagnosis to relapse was longer in the allo-HSCT vs non-HSCT cohort (17.0 vs 8.8 months; p = 0.003).

Allo-HSCT, allogeneic hematopoietic stem cell transplantation; GFRS, graft-versus-host disease-free survival; NRM, non-relapse mortality; OS, overall survival; RFS, relapse-free survival; RR, relapse rate
*Data from Nishiwaki, et al.¹

 

Key learnings
Allo-HSCT in first CR is associated with improved survival and a lower relapse rate in adult patients with Ph+ ALL who achieve complete molecular remission within 3 months. Further studies are needed to establish the role of allo-HSCT alongside newer generation TKIs, such as ponatinib.