Rationale of CPX-351 in t-AML

Rami Komrokji, MD:CPX-351, or liposomal cytarabine and daunorubicin, is a liposomal form of chemotherapy that, in preclinical studies, shows maximum efficacy or killing of the leukemia cells. This drug had been developed in phase I and phase II clinical studies. We observed that patients who had therapy-related AML or AML secondary from MDS had a potential survival benefit in the phase II setting. There was a phase III design with this medication that randomized patients who either had therapy-related AML or AML from antecedent MDS or AML with dysplastic changes or karyotypes similar to MDS. Those patients were randomized to standard chemotherapy, what we call 3 + 7, versus CPX-351. The primary endpoint was overall survival.

The study, in terms of efficacy, showed that there was an overall survival advantage in the patients who were treated with CPX-351. The response rates were higher with CPX-351. More patients were able to be bridged to allogeneic stem cell transplant. In terms of safety, the 30-day and 60-day mortality with CPX-351 was less than with intensive chemotherapy. This led to the approval of CPX-351 in patients we described, and that’s what we currently use it in patients with therapy-related AML.

What was presented at the 2018 ASCO Annual Meeting was a subset analysis of those patients who had the therapy-related AML. There were about 30 patients in each group who had therapy-related AML. This really demonstrated the same overall results in all of the groups—there was benefit with CPX-351 in terms of efficacy when compared with 3 + 7 chemotherapy.

Transcript edited for clarity.

Case: A 67-Year-Old Man with Therapy-Related AML

• A 67-year-old man who had received CHOP for diffuse large B-cell lymphoma 3 years prior
• PMH: hypertension controlled with amlodipine
• Laboratory results:
  • WBC 15 x 10⁹/L
  • Serum creatinine 1.5 mg/dL
  • Normal LFTs
  • LVEF 50%
• Diagnosis: Acute Myeloid Leukemia
• ECOG PS 1
• The patient received liposomal cytarabine and daunorubicin
• His course was complicated by febrile neutropenia
• After induction, <5% marrow blasts, neutrophil count (>1400/&micro;L), platelets 60,000/&micro;L