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A Phase 2 study of combination therapy with arsenic trioxide and gemtuzumab ozogamicin in patients with myelodysplastic syndromes or secondary acute myeloid leukemia
Author(s) -
Sekeres Mikkael A.,
Maciejewski Jaroslaw P.,
Erba Harry P.,
Afable Manuel,
Englehaupt Ricki,
Sobecks Ronald,
Advani Anjali,
Seel Sherry,
Chan Josephine,
Kalaycio Matt E.
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.25686
Subject(s) - medicine , myelodysplastic syndromes , gemtuzumab ozogamicin , neutropenia , febrile neutropenia , myeloid leukemia , international prognostic scoring system , oncology , chemotherapy , cd33 , bone marrow , stem cell , biology , cd34 , genetics
BACKGROUND: Higher‐risk myelodysplastic syndromes (MDS) are similar pathobiologically to acute myeloid leukemia (AML), particularly in older adults. AML therapies thus may have activity in MDS. In the current study, phase 2 study data of arsenic trioxide (ATO) and gemtuzumab ozogamicin (GO) in CD33‐positive patients with MDS and secondary AML (sAML) were presented. METHODS: Between June 2004 and February 2006, 30 patients with higher‐risk MDS or sAML received ATO (at a dose of 0.25 mg/kg intravenously for 5 days during Week 1, then twice weekly during Weeks 2‐12) and GO (at a dose of 3 mg/m 2 on Day 8) for 1 or 2 cycles of 12 weeks each. The primary endpoint was response as per MDS or AML International Working Group (IWG) criteria. Adverse events were collected throughout treatment. Patients were followed for a minimum of 3 years for survival. RESULTS: The median patient age was 69 years. A total of 18 patients had MDS, 12 had sAML, and 19 had been previously treated. Seventeen patients (57%) completed ≥1 cycle, and 7 patients (23%) completed 2 cycles. IWG responses occurred in 9 patients (30%) according to IWG MDS criteria (including 2 of 7 patients who failed hypomethylating agents) and 3 of 12 AML patients (25%) according to IWG AML criteria. Grade 3/4 (according to National Cancer Institute Common Toxicity Criteria [version 3.0]) thrombocytopenia occurred in 47% of patients, neutropenia in 63%, and anemia in 37% of patients. The median overall survival was 9.7 months (28.6 months in responders and 7.6 months in nonresponders; P <.001). Patients who completed 2 cycles of therapy spent a median of 13 days in the hospital. CONCLUSIONS: Combination therapy with ATO and GO was found to have acceptable response rates and toxicity, and may be a viable treatment option to standard induction therapy, particularly for patients who fail therapy with hypomethylating agents. Cancer 2011. © 2010 American Cancer Society.