CPX-351: Liposomal Cytarabine/Daunorubicin in Secondary AML

James K. McCloskey II, MD:For this patient who we’re seeing with AML-MRC [acute myeloid leukemia with myelodysplasia-related changes], over the age of 60, we certainly would be considering this patient for treatment with Vyxeos [liposomal cytarabine/daunorubicin]. If we look at the FDA approved label, this was approved for patients with AML-MRC as defined by the WHO [World Health Organization] criteria. Again, those would be patients that we mentioned who had AML with 20% blasts with either antecedent hematologic malignancies, some kind of MDS [myelodysplastic syndrome]-defining cytogenetic abnormality, or multilineage dysplasia. This was approved based on a phase III clinical trial that showed an improved overall survival for the specific niche of patients.

As I mentioned, this drug was approved by the FDA based on randomized phase III clinical trial results. I think when you look at the new drugs that have come to market for AML, it’s important to realize that many of those were not approved on randomized phase III results, but rather phase II unrandomized clinical trial results.

In this clinical trial, patients between the age of 60 and 75 were randomized to either Vyxeos, or 7+3 [cytarabine/daunorubicin], which has been our standard for patients with AML for decades. For patients who achieved remission with Vyxeos, they proceeded on with Vyxeos consolidation. In the 7+3 arm, patients who achieved a remission were eligible to continue on with 5+2 [cytarabine/daunorubicin] consolidation, which isn’t necessarily our standard here in the United States but is pretty typical in Europe. I think for many of us, it is reasonable for a patient over the age of 60 for a variety of reasons. It was also preferred when we looked at the design of the trial to try to keep anthracycline exposure similar between the 2 arms. But the drug was approved because it led to an improved overall survival in this very challenging-to-treat patient population with an improvement of the overall survival from 5.9 months in the 7+3 arm to 9.5 months in the Vyxeos-treated arm.

I think that when we look this data, it can be easy to blow off this improvement in overall survival—it’s a matter of 3 months. But the truth is that it took us 20 years to separate those 2 curves. When we started this conversation, these are some of the most challenging-to-treat patients with AML, and they have some of the worst prognosis. Shifting that curve, it’s certainly substantial. The clinical benefit of achieving a CR [complete remission] is not only meaningful in terms of that patient surviving longer and maybe having the opportunity to proceed to stem cell transplant, but also frankly improving their quality of life and reducing their need for transfusions and other things.

This benefit did not end in just overall survival for all patients, but if we look at patients who achieved a CR or CRi [complete remission with incomplete hematologic recovery], those patients in the Vyxeos arm also had improved overall survival. And even when we incorporate transplants, patients treated with Vyxeos had an improved overall survival post-transplant. In the 7 + 3 arm, the median overall survival was 11 months. The Vyxeos arm did not have a median overall survival that’s yet been met.

Whether we look at patients who did not go to transplant and had a CR, and even those patients who proceeded to transplant, those patients also received a survival benefit. This is certainly important especially if we think about taking a 65-year-old patient, putting them through induction chemotherapy, and proceeding to a stem cell transplant. Certainly, we want to know that those patients post-transplant are going to continue to do well, and that the relapse rate post-transplant and the survival post-transplant are hopefully improved for patients with a new drug like Vyxeos. I think that these data are promising and are going to continue to mature.

Transcript edited for clarity.

Case: A 68-Year-Old Man Withde novoAML

History and Physical:

• A 68-year-old man presented with significant fatigue and shortness of breath on exertion; reports low-grade fever for the past few days.
• PMH: mild hypertension, hypercholesterolemia, both medically managed; no history of malignancy

Laboratory work-up:

• WBC, 2.6 X 10⁹/L
• ANC, 1.2 X 10⁹/L
• Hb, 9.4 X 10⁹/L
• Hct, 32%
• RBC, 3.3 X 10⁹/L
• MCV, 121 fL
• PLT, 95 X 10⁹/L

Bone marrow biopsy:65% blasts

Peripheral blood smear;70% blasts

FISH;del(5q), del (20q)

Diagnosis;AML, myelodysplasia-related cytogenetic abnormalities