TOPLINE:

Preemptive azacitidine treatment guided by measurable residual disease (MRD) status was associated with delayed relapse in patients with myelodysplastic neoplasms or acute myeloid leukemia (AML), with more than half of initial responders remaining relapse-free for over 2 years. Among the 60 patients who were relapse-free at 6 months, 52% remained relapse-free for at least 2 years after initiating azacitidine, and 25% remained in remission after a median follow-up of 6.6 years.

METHODOLOGY:

• MRD predicts relapse after intensive chemotherapy or allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic neoplasms or AML. In the RELAZA2 trial, researchers evaluated whether MRD-guided preemptive azacitidine could prevent or delay hematologic relapse and improve long-term outcomes in patients in morphologic remission before hematologic relapse.
• This multicenter, phase 2 trial included 357 patients with myelodysplastic neoplasms or AML in complete remission after treatment who were screened for MRD using peripheral blood samples. MRD positivity was defined as CD34+ donor chimerism of less than 80% or NPM1 or RUNX1::RUNX1T1 mutations with a mutational burden of over 1%.
• Of 119 patients with MRD positivity during screening, 95 received preemptive azacitidine at 75 mg/m² subcutaneously on days 1-7 of each 28-day cycle for up to 2 years or until disease relapse.
• The primary endpoint was the proportion of patients alive and relapse-free 6 months after initiation of azacitidine; secondary endpoints included tolerability, safety, relapse-free survival, and overall survival for up to 60 months. The current study reported the final long-term results of the trial.

TAKEAWAY:

• Among patients who received azacitidine, 63% (60 of 95) were relapse-free at 6 months after treatment initiation; among them, 39 (65%) achieved a major MRD response, and 14 of 19 evaluable major responders achieved MRD negativity.
• Of the 60 initial responders, 31 (52%) maintained response without hematologic relapse for at least 2 years after treatment initiation. After a median follow-up of 6.6 years, 25% of initial responders were still in remission.
• Lower MRD levels at treatment onset (odds ratio [OR], 40.3), longer time since last therapy (OR, 1.1), and a favorable European LeukemiaNet 2010 risk group (OR, 4.28) were associated with improved response to azacitidine treatment.
• Regarding the safety and tolerability of azacitidine, grade 3-4 neutropenia occurred in 94% of patients and thrombocytopenia in 18%. Infections and gastrointestinal toxicity were the most common serious nonhematologic events. Overall, 13 patients (14%) required dose reductions, 66 (69%) had cycle delays, and one death was possibly related to azacitidine.

IN PRACTICE:

“Our findings support incorporating regular MRD monitoring into routine clinical practice, potentially reshaping treatment strategies and patient management in hematological malignancies by emphasizing a more personalized approach based on MRD status and level,” the study authors wrote.

SOURCE:

The study, led by Anne Sophie Platzbecker, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany, was published online in Blood.

LIMITATIONS:

The study was initiated before publication of the European LeukemiaNet consensus recommendations on MRD, so the protocol included both molecular thresholds and CD34+ donor chimerism to define imminent relapse. Detailed information on transplantation modalities was lacking. Additionally, retrospective comparisons were hampered by the lack of standardized MRD testing and incomplete documentation of outcomes in patients with MRD positivity who were not treated during the same period.

DISCLOSURES:

The study received support from the José Carreras Leukaemia Foundation, the German Cancer Consortium Foundation, the National Center for Tumor Diseases Dresden, Celgene Corporation (now Bristol Myers Squibb [BMS]), and Novartis. Platzbecker declared receiving research funding and lecture fees from Johnson & Johnson, BMS, Novartis, and Curis outside the submitted work. Several authors declared receiving grants or personal fees or having other ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.