Significance of Measurable Residual Disease in Adult Philadelphia Chromosome-Positive ALL: A GRAAPH-2014 Study.

PURPOSE

quantification is widely regarded as the standard for monitoring measurable residual disease (MRD) in Philadelphia chromosome-positive (Ph+) ALL. However, recent evidence of multilineage involvement questions the significance of MRD. We aimed to define the prognostic role of MRD as assessed by or lymphoid-specific immunoglobulin/T-cell receptor () gene markers.

PATIENTS AND METHODS

We conducted and quantification after each treatment cycle in 264 patients treated in the GRAAPH-2014 trial, which used four cycles of reduced-intensity chemotherapy with nilotinib, followed by hematopoietic stem-cell transplantation (HSCT).

RESULTS

Comparing and MRD revealed residual -positive non-ALL cells in 98 (43%) of 228 patients, defining multilineage Ph+ ALL. Despite poorer responses, patients with multilineage Ph+ ALL had similar disease-free survival (DFS; hazard ratio [HR], 0.83 [95% CI, 0.49 to 1.41]; = .50). Although response failed to predict outcomes, positivity (≥0.01%) was strongly associated with lower DFS (after cycle 2, HR, 2.49 [95% CI, 1.40 to 4.40]; = .002; after cycle 4, HR, 4.13 [95% CI, 1.82 to 9.38]; = .001). In multivariable analysis, both positivity after cycle 2 and initial WBC count ≥30 × 10/L predicted poorer DFS, enabling to define a high-risk group having a 4-year DFS of 56.5% compared with 87.6% (HR, 3.72 [95% CI, 1.93 to 7.15]; < .001). Moreover, allogeneic HSCT significantly improved DFS in the high-risk group (HR, 0.33 [95% CI, 0.18 to 0.60]; < .001), whereas the standard-risk group had favorable outcomes regardless of allogeneic HSCT.

CONCLUSION

Our findings challenge the significance of monitoring in adult Ph+ ALL and demonstrate the prognostic role of MRD. This study provides a framework for using MRD to guide treatment strategies in adults with Ph+ ALL.