Correlation between MRD at the end of induction and EFS in pediatric T-cell lymphoblastic lymphoma

Measurable residual disease (MRD), a test used to detect the presence of lymphoma cells after therapy has shown prognostic significance in both B-cell and T-cell acute lymphoblastic leukemia. However, the correlation between end-of-induction (EOI) MRD and clinical outcomes in patients with T-cell lymphoblastic lymphoma (T-LBL) remains unclear.

Here, we summarize a subgroup analysis of the phase III Children’s Oncology Group AALL1231 trial published by Hayashi et al.¹ in Blood assessing the correlation between EOI MRD and event-free survival (EFS) in patients with T-LBL.

Study design¹

• This was a phase III trial of patients with newly diagnosed Stages II–IV T-cell acute lymphoblastic leukemia or T-LBL
  • Children and young adults were randomized to either the standard therapy arm (A) or with the addition of bortezomib (B)
• Patients with T-LBL who were enrolled in the AALL1231 trial were invited to submit bone marrow samples after induction therapy.
• The primary endpoint was EFS; other endpoints included overall survival (OS).

Key findings¹

• A total of 86 out of the 209 patients with T-LBL volunteered to submit samples, representing 41% of the total population.
• Patients with an MRD of <0.1% (n = 75) at the end of induction experienced a higher four-year EFS rate vs patients with MRD ≥0.1% (n = 11) (Figure 1).
• A significant difference in EFS rates was also observed by treatment arm with patients receiving bortezomib experiencing higher EFS.
• There was no significant difference in overall survival rates by MRD status.
• A significant difference in OS was observed between treatment arms A and B, with those also receiving bortezomib experiencing increased OS rates.
• MRD EOI of ≥0.1% was associated with a lower EFS, irrespective of treatment arm [hazard ratio of 3.73 (1.120–12.4; p = 0.032).
  • There was no significant difference in EFS between treatment arms or increasing MRD at diagnosis.

EFS, event-free survival; MRD, measurable residual disease; OS, overall survival.  
*Data from Hayashi, et al.¹ 

Key learnings

MRD <0.1% in the bone marrow at the EOI was significantly associated with increased EFS rates in patients with T-cell lymphoblastic lymphoma, regardless of the treatment arm. Data from this trial provides evidence for assessing MRD at the end of induction therapy to identify patients at risk for treatment failure. More research is required to determine the value of EOI MRD to define risk groups for EFS.