Rationale of CPX-351 in t-AML

Video

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
Related Videos
John Mascarenhas, MD, an expert on myelofibrosis
John Mascarenhas, MD, an expert on myelofibrosis
John Mascarenhas, MD, an expert on myelofibrosis
John Mascarenhas, MD, an expert on myelofibrosis
John Mascarenhas, MD, an expert on myelofibrosis
John Mascarenhas, MD, an expert on myelofibrosis
John Mascarenhas, MD, an expert on myelofibrosis
Related Content