Selecting the Right Patients for CPX-351 or Venetoclax + Azacitidine 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

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

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

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: I want to ask you 1 more question about [a transplant for] this patient. If the patient were younger and had bland mutations, a normal karyotype, and a TET2 mutation, would you [recommend the] transplant just because they had secondary AML [acute myeloid leukemia] and they’re in remission?

Eunice Wang, MD: If she were a little younger, had normal karyotype and a TET2 [mutation], and didn’t have the history of breast cancer, we’d think that she was at intermediate risk. At our center, we lean toward recommending transplants for all patients who aren’t at favorable risk. We know that about half of patients at intermediate risk are going to have recurrence. Without the history, she’d be in the better category. We’d still consider transplant for her. Then it may come down to what her donor status is and whether she’s interested. I believe that transplant offers the best consolidative method to cure in many individuals, but it isn’t 100% necessary. As you said, if she had an MLL [mixed lineage leukemia], complex karyotype, or TP53 mutation, then it would be definite. There would be room for discussion in her case. As you said, if she were 45 or 50 [years old] and not over 60 [years old], she could do well with 7+3.

Richard Stone, MD: I agree. We recommend transplants for our patients at intermediate risk as well. We’d recommend a transplant for this patient regardless of her age [or mutations].

Eunice Wang, MD: The only issue I have: You could give 7+3. There are some quality-of-life data that say CPX-351 would be better than 7+3 in terms of quality-of-life issues and time in remission. I don’t know about your center, but some centers give the CPX-351 in the outpatient setting because it’s intermittent dosing on days 1, 3, and 5, which cuts a week off their inpatient stay. There are people who argue that CPX-351 would be better than 7+3 because of quality-of-life issues, ambulatory [issues], time in remission, etc. This could also be discussed.

It’s interesting that you mention TP53 and venetoclax-azacitidine, because there have been some post hoc retrospective abstracts presented at the ASH [American Society of Hematology] [Annual Meeting] that have tried to figure out for older patients whether venetoclax-azacitidine or CPX-351 would be better. I don’t know if you want to address some of the findings of those, because they’re retrospective, but they’re interesting.

Richard Stone, MD: The [Weill] Cornell [Medicine] study by Justin Grenet, [MD,] et al looked at patients aged 60 to 75 [years] who, in the retrospective analysis, got either CPX-351 or venetoclax-azacitidine. Although there was no difference in overall survival, there seemed to be a better outcome for the patients with TP53 mutation who were treated with CPX-351, which I found surprising and rejected from my belief system. But those are the data they showed.

The people at Penn and 1 other group presented a retrospective analysis of CPX-351 vs venetoclax-azacitidine, and people reasonably could have gotten both. It’s a highly biased analysis because people who got venetoclax-azacitidine were generally older and less fit. It seemed to show no difference in outcome whether they got venetoclax-azacitidine or CPX-351, implying that you could use venetoclax-azacitidine for most patients who could get either. That’s dubious in its conclusion. I don’t think anybody I know would have treated the patient that you presented with venetoclax-azacitidine, but the data you cited would support it. Do you think we’re moving to venetoclax-azacitidine for a wider group of patients?

Eunice Wang, MD: If you have a young patient, complex karyotype, and TP53 mutations, people have advocated for venetoclax-azacitidine. As you said, it’s less toxic and maybe safer, and you potentially don’t have the damage to the mucosal membranes and same risk of gram-negative rod sepsis and bacteremia that you do with venetoclax-azacitidine. People have argued that venetoclax-azacitidine may be a safer way to get patients to undergo transplant because of the toxicities and decreased stay.

However, these 3 or 4 retrospective abstracts that essentially came up with the same thing were a little flawed because the patient populations in each of these studies were very distinct, as you mentioned. Older patients got venetoclax-azacitidine. Less fit patients got venetoclax-azacitidine. Younger, more fit people got CPX-351. With many of those abstracts, the only conclusion I made was that it didn’t matter what induction you got. If you had secondary AML or therapy-related AML and you underwent transplant, you had the best outcomes. With younger patients, maybe those with TP53 mutations, if you can give them CPX-351, the overall survival may be better. If you can’t give them CPX-351, then azacitidine is a reasonable alternative. But as I said, it didn’t persuade me to give my 62-year-old or 55-year-old patient venetoclax-azacitidine. The data aren’t out there, and our transplant outcome data aren’t out there. I don’t feel 100% comfortable in that setting.

Richard Stone, MD: I agree with you. It’s ironic you think that because of the distinct patient populations and the fact that, by and large, patients with more severe disease would have gotten venetoclax-azacitidine compared with CPX-351, and the results were equivalent in most cases. It certainly supports venetoclax-azacitidine in a wider scope because it was able to do well, even compared with a younger patient population. It’s going to take more time and more studies.

Transcript edited for clarity.