Testing for minimal residual disease (MRD) has been available for years now in hematological malignancies. Despite the availability of MRD testing, most oncologists and hematologists do not often use it in clinical practice. The reason, they will tell you, is that they don’t know what to do with the information; that is, results of MRD testing may be prognostic, but they don’t change the management of the patient. And if you aren’t going to use MRD test results to change management, why spend the money on getting the test in the first place?
Two recent publications in The New England Journal of Medicine suggest the potential for MRD testing to affect management in patients with multiple myeloma and chronic lymphocytic leukemia (CLL). In the first, called the MIDAS trial (NCT04934475), patients with multiple myeloma were treated with a quadruplet regimen consisting of isatuximab (Sarclisa), carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone. When measured prior to maintenance, patients treated with the quadruplet regimen (and no autologous stem cell transplant [ASCT]) had essentially the same rate of undetectable MRD at 10–6 sensitivity (84%) as did patients treated with ASCT plus 2 cycles of the quadruplet regimen (86%). The results suggest that perhaps ASCT does not add much value, and therefore could be omitted, in patients who achieve undetectable MRD after induction therapy with a quadruplet regimen.
The second trial in which the results of MRD testing affected practice was the FLAIR trial (NCT02938520). Earlier results of FLAIR had been published and evaluated the doublet of ibrutinib (Imbruvica) plus venetoclax (Venclexta). In the latest report, the doublet was also compared with single-agent ibrutinib. In the patients treated with the doublet, about half achieved undetectable MRD after 1 year of therapy. The doublet improved both progression-free survival and overall survival compared with single-agent ibrutinib.
This is the first trial to suggest that any frontline treatment of CLL could improve survival compared with a single-agent Bruton tyrosine kinase inhibitor, and it suggests that the results of MRD testing could be used to determine an appropriate duration of therapy with the doublet. At a minimum, we are starting to see fulfillment that MRD testing could be used to affect patient management.