A Phase 2 study of combination therapy with arsenic trioxide and gemtuzumab ozogamicin in patients with myelodysplastic syndromes or secondary acute myeloid leukemia

• Published in: Cancer Vol. 117; no. 6; pp. 1253 - 1261
• Main Authors: Sekeres, Mikkael A., Maciejewski, Jaroslaw P., Erba, Harry P., Afable, Manuel, Englehaupt, Ricki, Sobecks, Ronald, Advani, Anjali, Seel, Sherry, Chan, Josephine, Kalaycio, Matt E.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.03.2011; Wiley-Blackwell
• Subjects: acute myeloid leukemia; Adult; Aged; Aged, 80 and over; Aminoglycosides - administration & dosage; Aminoglycosides - adverse effects; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; arsenic trioxide; Arsenicals - administration & dosage; Arsenicals - adverse effects; Biological and medical sciences; clinical trial; Drug Administration Schedule; Female; gemtuzumab ozogamicin; Hematologic and hematopoietic diseases; Humans; Leukemia, Myeloid, Acute - drug therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; myelodysplastic syndromes; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - pathology; Neoplasms, Second Primary - drug therapy; Oxides - administration & dosage; Oxides - adverse effects; Salvage Therapy; Treatment Outcome; Tumors; Antineoplastic agent; Human; Immunochemotherapy; Acute myelogenous leukemia; Secondary; Arsenic trioxide; Malignant hemopathy; Monoclonal antibody; Ozogamicin; Myelodysplastic syndrome; Chemotherapy; Treatment; Cancerology; acute myeloid leukemia; Phase II trial; myelodysplastic syndromes; Clinical trial; Combined treatment; Cancer; gemtuzumab ozogamicin
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.25686

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/m2 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. This Phase 2 study explored the safety and efficacy of combination therapy with arsenic trioxide (ATO) and gemtuzumab ozogamicin (GO) in patients with higher‐risk myelodysplastic syndromes (MDS) or secondary (arising from MDS) acute myeloid leukemia. The outpatient regimen of ATO plus GO represents a reasonable alternative to remission induction therapy, and a novel approach to treating patients who have failed standard hypomethylator therapy for higher‐risk MDS.