Acute Myeloid Leukemia: Frontline Treatment With CPX-351

Transcript:

Jorge E. Cortes, MD: Speaking about chemotherapy, and moving on because we can certainly prolong these as much as we want, because it’s very interesting and there are many items for discussion.One interesting chemotherapy agent, which is a reformulated chemotherapy, is the CPX-351 or Vyxeos, which is a liposomally encapsulated combination of cytarabine and daunorubicin. The argument here is that by keeping that 5:1 molar ratio, it provides optimal antileukemia effect. In animal studies, it looks impressive compared to the free drugs in terms of the cure of these animals. This was taken from the initial phase 2 studies where there was the suggestion of benefit for…newly diagnosed patients with secondary leukemias, either secondary from other cancers or from MDS [myelodysplastic syndrome]. That study was surprisingly very positive, not only in terms of the response rate that was significantly better for the patients treated with CPX, but also in terms of the survival, where the median survival was about 30% higher, like 9 months compared to a little under 6 months. Then a recent update shows that at 5 years you have 18%, which is not great, but it’s compared to 8% with 3+7 [chemotherapy regimen]. Even for patients who were transplanted, the survival is better for the patients who got a remission and got a transplant if they received the CPX compared to the 3+7.

The drug seems to be fairly well tolerated, more myelosuppression, but otherwise well tolerated. It’s an interesting concept that with a liposomal encapsulation you could deliver the same chemotherapy better. That has now become standard. It was approved for these secondary leukemias. Interestingly, the study was for older patients, 60 to 75. It’s approved for all patients, but it’s an intensive therapy that proved you can treat these patients who are older, 60, 65, all the way to 75, with intensive chemotherapy, if they are fit for chemotherapy. This is an interesting approach. It’s one of these recently approved drugs for AML [acute myeloid leukemia]. Do you use it, is that your standard in secondary leukemias, Hetty? Is that what you use in the clinic for these patients?

Hetty E. Carraway, MD: We’ve been fortunate to have an ongoing clinical trial using CPX in combination with another investigative agent in patients with upfront AML and secondary AML. That has predominantly been a pathway for us, and is fortunately part of a clinical trial, so we’ve gotten lots of experience with CPX-351. The patient population that I think warrants consideration for this agent is what you’ve just described: patients between 60 and 75 with secondary AML or even MDS that has progressed to AML. Some of the patients we also know to benefit from this liposomal version are patients with NPM1 mutations. Those patients also seem to have a better outcome even in a post-transplant setting, if I’m not mistaken. Certainly, those patients for whom we have a high suspicion that they’re headed to transplant, those patients as you described, did better in the post-transplant setting, and it seemed based on the data that they had fewer relapses due to disease specifically. We were challenged by thrombocytopenia in that patient population, and prolonged neutropenia, so it has to be with a right patient because there were episodes of bleeding and hemorrhage for some of those patients that were difficult. We are typically challenged by that in any mechanism that we’re treating our patients with unless we’re using specific agents that target mutations like IDH that are not causing prolonged issues with pancytopenia. I think it’s a nice agent.

Some of the things that we are challenged by are the financial toxicity of this agent, and as a result of that there have been institutions that have successfully been able to give CPX-351 in the outpatient setting. I can see Dr Kasner raising her hand, maybe she wants to walk us through that. Those must be unique centers that have the transfusion support, the ability to deal with febrile neutropenia, and the ability to deal with fevers, which will likely happen with administration of this agent. You must have a patient that is close to a center that’s able to support them in the outpatient center with that type of approach.

Jorge E. Cortes, MD: Do you want to tell us how you manage those things, Dr. Kasner?

Margaret T. Kasner, MD: Sure, and I agree that it is not every center, but if you want to do it, there’s almost a formula for how to do it. It starts with having somebody who can be there close by for at least the initial administration. We require our patients to come every day for 5 days, although it’s a Monday, Wednesday, Friday, or any 3 days, alternating therapy. That is because in the intermediate days there is the risk of tumor lysis, simply not feeling well, not staying well hydrated, and all of those things that might threaten your ability to stay in the outpatient setting. So we highly rely on our patient services to help provide them with discounted housing close by if they are not able to live within a close enough distance. The other part of it is the support. You need a cadre of nurse practitioners and nurses who can field calls, who can deal with the transfusion support issues, because as academicians we’re not in the clinic 7 days a week, but we do have a 7-day-a-week infusion center. So having that support is incredibly important.

The other half is the partnership with the patient. They must understand all of things that they need to do, and you can boil it down to, if you have a fever you must go to the emergency department. But it’s nice that they’ll communicate with you about all of the issues that are going on with them and to have people who can answer all of those calls. It’s not for every patient, and it’s not for every infusion center, but it’s been very successful. We have a paper that describes our setting, UCLA [University of California Los Angeles] and Hackensack [Meridian Health], because we all approach our patients the same way, which is we don’t plan to readmit them. We give them outpatient therapy, and then we let them see how things go. That will hopefully be published in the first part of 2023. After that everybody can call us, and we’ll be happy to help setting up your center.

Jorge E. Cortes, MD: I’m looking forward to seeing this paper.

Transcript edited for clarity.