A phase 2 study of ATRA, arsenic trioxide, and gemtuzumab ozogamicin in patients with high-risk APL (SWOG 0535).

Journal Article (Journal Article)

High-risk acute promyelocytic leukemia (APL) remains a therapeutic challenge, with higher associated rates of early mortality and relapse than standard-risk APL. All-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) is a well-established treatment for patients with standard-risk APL, but it is not well defined for those with high-risk APL. In a prior study of patients with high-risk APL, the addition of gemtuzumab ozogamicin (GO) to ATO plus ATRA suggested benefit. The SWOG Cancer Research Network conducted a phase 2 study to confirm the efficacy and safety of the combination of ATRA plus ATO plus GO in treating high-risk APL patients. The primary end points were 3-year event-free survival (EFS) and early (6-week) death rates associated with this combination. Seventy patients were treated. With a median follow-up of 3.4 years, the 3-year EFS and overall survival estimates were 78% (95% confidence interval [CI], 67%-86%) and 86% (95% CI, 75%-92%), respectively. Overall, 86% of patients achieved complete response. The 6-week mortality rate was 11%. The most common treatment-emergent toxicities during the induction phase included febrile neutropenia, aspartate aminotransferase/alanine aminotransferase elevation, hyperglycemia, hypoxia, headache, and prolonged QT interval corrected for heart rate. Retinoic acid syndrome occurred in 9% of patients. Approximately 37% of patients did not complete all planned courses of postremission therapy. The combination of ATRA plus ATO plus GO in high-risk APL patients was effective and generally well tolerated, suggesting an opportunity to offer a chemotherapy-free induction platform for patients with this disease. This trial was registered at www.clinicaltrials.gov as #NCT00551460.

Full Text

Duke Authors

Cited Authors

  • Lancet, JE; Moseley, AB; Coutre, SE; DeAngelo, DJ; Othus, M; Tallman, MS; Litzow, MR; Komrokji, RS; Erba, HP; Appelbaum, FR

Published Date

  • April 2020

Published In

Volume / Issue

  • 4 / 8

Start / End Page

  • 1683 - 1689

PubMed ID

  • 32330241

Pubmed Central ID

  • PMC7189292

Electronic International Standard Serial Number (EISSN)

  • 2473-9537

International Standard Serial Number (ISSN)

  • 2473-9529

Digital Object Identifier (DOI)

  • 10.1182/bloodadvances.2019001278


  • eng