Role of MRD in Treatment Decision Making in AML

EP: 1.Secondary Acute Myeloid Leukemia (AML): Overview

EP: 2.Patient Profile 1: Patient with Secondary Acute Myeloid Leukemia

EP: 3.CPX-351 in Treatment of AML and Clinical Considerations

EP: 4.Selecting the Right Patients for CPX-351 or Venetoclax + Azacitidine in AML

EP: 5.Considerations for Venetoclax + Azacitidine Administration and AE Management

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EP: 6.Role of MRD in Treatment Decision Making in AML

EP: 7.Patient Profile 2: Patient with de novo AML and IDH2 Mutation

EP: 8.Importance of Molecular Testing in Acute Myeloid Leukemia to Guide Treatment

EP: 9.Targeted Therapy in Patients with AML and IDH1/IDH2 Mutations

EP: 10.Unmet Needs and Future Perspectives in 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.