My Treatment Approach: Acute Myeloid Leukemia (AML) - Episode 6

Role of MRD in Treatment Decision Making in AML


Two experts discuss the clinical implications of minimal residual disease (MRD) and how it has affected treatment for patients with acute myeloid leukemia (AML).

Richard Stone, MD: One thing we could look at is measurable residual disease [MRD] or minimal residual disease. I have 2 questions about it. The first is: Why do you think the results of patients who got transplanted and received CPX-351 before the transplant were better than those who got transplanted but received 7+3 before the transplant in Dr Lancet’s study [NCT01696084] comparing the two?­­

Eunice Wang, MD: Even in the 5-year follow-up study, the presumption is that because of the different pharmacokinetics of the drug, as you very aptly pointed out, the CPX-351 penetrates into the bone marrow and is retained in the bone marrow for much longer than standard 7+3. In standard 7+3, the half-life of cytarabine in vivo in patients is 7 to 20 minutes, which is why we have to give it via continuous infusion. With CPX-351, the half-life of the cytarabine is much longer and much more durable.

The implication is that the CPX-351 achieved a much deeper response, or potentially a higher incidence of MRD negativity, than 7+3 did, and therefore that would account for the difference in the post-transplant post hoc analysis. There are no data to support that, but there are data in many other settings supporting that MRD negativity following standard 7+3 chemotherapy at any point is very predictive of outcome.

Interestingly, in these retrospective analyses, one of the reasons that venetoclax-azacitidine and CPX-351 resulted in similar CR [complete response] rates and relapse-free survival rates is because the MRD negativity rate, at least in Dr Justin Grenet’s [, MD, Weill Cornell Medical College,] study, was 60% in CPX-351–treated patients and 60% in the venetoclax-azacitidine–treated patients. The identical outcomes could have purely been due to the similarities in MRD achievement. MRD is an important marker in terms of being able to go on to a successful allogeneic stem cell transplantation and remain in remission and probably durability of response for patients who can’t go to transplant.

Richard Stone, MD: I absolutely agree with you. The fact that the MRD rates were high and equivalent certainly supports azacitidine-venetoclax being a major player in this field going forward. If it’s a little less toxic, absolutely, although CPX-351 isn’t too bad in terms of toxicity. There isn’t much hair loss, and GI [gastrointestinal] toxicity isn’t usually bad. It’s more myelosuppressive for the reasons you just talked about. Let’s go back one slide to see what happened to this patient.

Eunice Wang, MD: This patient was administered induction chemotherapy with CPX-351. This was complicated with fibral neutropenia, which was treated with broad-spectrum antibiotics. I’d like to point out that CPX-351 results in very similar toxicities to standard 7+3, with the exception being more prolonged cytopenias, and particularly thrombocytopenia in patients receiving CPX-351. The patient achieved a morphological CR. They didn’t comment on MRD status. That’s just something that we’re doing as standard of care. She got a couple of cycles of consolidation with CPX-351 while awaiting a matched unrelated stem cell transplantation. She underwent transplant and remains in CR at the time of this case presentation.

Transcript edited for clarity.