Residual disease in AML patients prior to stem cell transplant increases relapse risk

For patients with acute myeloid leukaemia (AML), the presence of measurable residual disease (MRD) prior to stem cell transplant significantly increases the risk of relapse among patients who receive a reduced-intensity conditioning regimen, compared with those with no MRD. This suggests that patients with evidence of MRD should receive higher-intensity conditioning, say researchers reporting a new analysis from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0901 [1].

In the late-breaking abstracts session, Dr Christopher Hourigan (NIH, USA) presented the results of preconditioning samples from 188 AML patients in the 0901 trial. The patients were well matched with respect to baseline characteristics, including age, sex, disease risk, donor type, donor match, and graft type.

A previous analysis of this study compared the outcomes of AML patients in remission, following 1 of 2 forms of pre-transplant preparative therapy, either high-intensity myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC), relapsed within 18 months after transplant [2]. They found that 31% of patients in the high-intensity myeloablative group and 33% in the reduced-intensity group had no genomic variants indicative of MRD. Subsequent survival rates did not differ among those groups (3-year overall survival: 58% vs 65%; P=0.98). However, among the patients with detectable variants indicative of MRD prior to conditioning, the 3-year overall survival rate was significantly better for the patients in the high-intensity conditioning group than for those in the reduced-intensity group (61% vs 44%; P=0.02).

The researchers assessed MRD using a next-generation, ultra-deep, error-corrected genomic sequencing technology that is currently available only for research purposes, Dr Hourigan explained. However, he said the findings underscore a role for MRD testing in the future. Overall, 76% of patients who experienced relapse had at least 1 detectable variant prior to conditioning. After adjusting for factors that included the level of disease risk and donor group, patients with detectable variants indicating MRD who went on to receive the reduced-intensity conditioning had a nearly 6 times greater risk for relapse (HR 5.98; 95% CI 3.19-11.26; P<0.001).

For these patients, disease-free survival was significantly decreased (HR 2.80; 95% CI 1.76-4.44; P<0.001), as was overall survival (HR 2.16; 95% CI 1.30-3.60; P=0.003), when compared with the higher-intensity conditioning group. Although in the original trial mortality related to toxicity from the treatment itself was significantly higher among the patients who received the high-intensity regimen, the new findings suggest the risk/benefit balance may be offset by this MRD finding, said Dr Hourigan.

"As a physician who treats acute leukaemia patients, these findings for me open up many interesting questions and some obvious opportunities for potentially improving the therapeutic outcomes for our AML patients," Dr Hourigan concluded.

1. 
   
   1. Hourigan C, et al. Abstract LB2600, 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.
   2. Scott BL, et al. J Clin Oncol. 2017 Apr 10;35(11):1154-1161.

Posted on 9 August, 20194 March, 2021