Detecting minimal residual disease may act as ‘surrogate endpoint’ for drug approvals

Gwen Nichols

ATLANTA — Research is ramping up to find the best way to detect minimal residual disease in patients with acute myeloid leukemia, according to Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society.

Nichols spoke with HemOnc Today following a presentation by Tim Grob, MD, of the department of hematology at Erasmus University Medical Center in Rotterdam, Netherlands, at the ASH Annual Meeting and Exposition.

Grob and colleagues demonstrated that the detection of molecular minimal residual disease by next-generation sequencing remained highly prognostic for relapse and survival among patients with newly diagnosed acute myeloid leukemia.

“We're doing a lot of research to try and find out the best way to check for minimal residual disease and to use it as what we call a surrogate endpoint for approval of new drugs,” Nichols said in an interview. “So, not only [are the drugs being assessed] effective in shrinking the disease, but also effective in eliminating all evidence of the disease in the body.”

Additionally, study results demonstrated that the presence of next-generation sequencing MRD predicted risk for reduced survival in a training cohort (HR = 1.64; 95% CI, 1.12-2.42) and validation cohort (HR = 3.08; 95% CI, 1.87-5.08).

“[These results] are extremely important, particularly in those diseases where we're now having really good responses with our therapies to know who is the most likely to be cured of their disease, versus those where the disease may relapse in the future,” Nichols said. “This will allow us to consider therapies to intervene as early as possible, and we know the least amount of disease is the easiest to treat.”

Nichols acknowledged that the Leukemia & Lymphoma Society is supporting a significant amount of research on the testing and identification of minimal residual disease.

“For this to be a validated endpoint, we need consistent tests, reproducible tests, and ones that the regulators will be able to look at and feel confident that the test is done properly so that the results are really meaningful,” she said.

Additionally, Nichols said more clinical trials need to use MRD testing to help determine what therapies are better than others with deeper response rates as well as possible cures or at least long-term, disease-free survival.

“The key is going to be following up to be sure that there is no evidence of the disease by this very sensitive genomic testing that will actually tell the physician that the patient will live longer,” she said. – by Ryan McDonald

Reference:

Jongen-Lavrencic M, et al. LBA-5. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.

Disclosures: Nichols reports that the Leukemia & Lymphoma Society grants research funding to various clinical trials.