Cancer Medicine (May 2020)

Clofarabine, cytarabine, and mitoxantrone in refractory/relapsed acute myeloid leukemia: High response rates and effective bridge to allogeneic hematopoietic stem cell transplantation

  • Harinder Gill,
  • Rita Yim,
  • Herbert H. Pang,
  • Paul Lee,
  • Thomas S. Y. Chan,
  • Yu‐Yan Hwang,
  • Garret M. K. Leung,
  • Ho‐Wan Ip,
  • Rock Y. Y. Leung,
  • Sze‐Fai Yip,
  • Bonnie Kho,
  • Harold K. K. Lee,
  • Vivien Mak,
  • Chi‐Chung Chan,
  • June S. M. Lau,
  • Chi‐Kuen Lau,
  • Shek‐Yin Lin,
  • Raymond S. M. Wong,
  • Wa Li,
  • Edmond S. K. Ma,
  • Jun Li,
  • Gianni Panagiotou,
  • Joycelyn P. Y. Sim,
  • Albert K. W. Lie,
  • Yok‐Lam Kwong

DOI
https://doi.org/10.1002/cam4.2865
Journal volume & issue
Vol. 9, no. 10
pp. 3371 – 3382

Abstract

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Abstract Clofarabine is active in refractory/relapsed acute myeloid leukemia (AML). In this phase 2 study, we treated 18‐ to 65‐year‐old AML patients refractory to first‐line 3 + 7 daunorubicin/cytarabine induction or relapsing after 3 + 7 induction and high‐dose cytarabine consolidation, with clofarabine (30 mg/m2/d, Days 1‐5), cytarabine (750 mg/m2/d, Days 1‐5), and mitoxantrone (12 mg/m2/d, Days 3‐5) (CLAM). Patients achieving remission received up to two consolidation cycles of 50% CLAM, with eligible cases bridged to allogeneic hematopoietic stem cell transplantation (allo‐HSCT). The mutational profile of a 69‐gene panel was evaluated. Twenty‐six men and 26 women at a median age of 46 (22‐65) years were treated. The overall response rate after the first cycle of CLAM was 90.4% (complete remission, CR: 69.2%; CR with incomplete hematologic recovery, CRi: 21.2%). Twenty‐two CR/CRi patients underwent allo‐HSCT. The 2‐year overall survival (OS), relapse‐free survival (RFS), and event‐free survival (EFS) were 65.8%, 45.7%, and 40.2%, respectively. Multivariate analyses showed that superior OS was associated with CR after CLAM (P = .005) and allo‐HSCT (P = .005), and superior RFS and EFS were associated with allo‐HSCT (P < .001). Remarkably, CR after CLAM and allo‐HSCT resulted in 2‐year OS of 84.3% and 90%, respectively. Karyotypic aberrations and genetic mutations did not influence responses or survivals. Grade 3/4 neutropenia/thrombocytopenia and grade 3 febrile neutropenia occurred in all cases. Other nonhematologic toxicities were mild and uncommon. There was no treatment‐related mortality and the performance of allo‐HSCT was not compromised. Clofarabine, cytarabine, and mitoxantrone was highly effective and safe in refractory/relapsed AML. This study was registered at ClinicalTrials.gov (NCT02686593).

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