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Phase III Randomized Multicenter Study of a Humanized Anti-CD33 Monoclonal Antibody, Lintuzumab, in Combination With Chemotherapy, Versus Chemotherapy Alone in Patients With Refractory or First-Relapsed Acute Myeloid Leukemia

From the Weill Medical College of Cornell University, New York, NY; Memorial Sloan-Kettering Cancer Center, New York, NY; Princess Margaret Hospital, Toronto, Ontario, Canada; Dana Farber Cancer Institute, Boston, MA; The Cleveland Clinic Foundation, Cleveland, OH; Duke University Medical Center, Durham, NC; Johns Hopkins Oncology Center, Baltimore; Greenebaum Cancer Center-University of Maryland, Baltimore, MD; Christie Hospital, Manchester, UK; Washington University, St Louis, MO; M.S. Hershey Medical Center, Hershey, PA; North Shore University Hospital, Manhasset, NY; and Protein Design Laboratories, Fremont, CA

Address reprint requests to Eric J. Feldman, MD, Weill Medical Collegeof Cornell University, 525 E 68th St, New York, NY 10021; e-mail: ejf2001{at}med.cornell.edu

PURPOSE: Lintuzumab (HuM195) is an unconjugated humanized murine monoclonal antibody directed against the cell surface myelomonocytic differentiation antigen CD33. In this study, the efficacy of lintuzumab in combination with induction chemotherapy was compared with chemotherapy alone in adults with first relapsed or primary refractory acute myeloid leukemia (AML).

PATIENTS AND METHODS: Patients with relapsed or primary resistant AML (duration of first response, zero to 12 months) were randomly assigned to receive either mitoxantrone 8 mg/m², etoposide 80 mg/m², and cytarabine 1 g/m² daily for 6 days (MEC) in combination with lintuzumab 12 mg/m², or MEC alone. Overall response, defined as the rate of complete remission (CR) and CR with incomplete platelet recovery (CRp), was the primary end point of the study, with additional analyses of survival time and toxicity.

RESULTS: A total of 191 patients were randomly assigned from November 1999 to April 2001. The percent CR plus CRp with MEC plus lintuzumab was 36% v 28% in patients treated with MEC alone (P = .28). The overall median survival was 156 days and was not different in the two arms of the study. Apart from mild antibody infusion–related toxicities (fever, chills, and hypotension), no differences in chemotherapy-related adverse effects, including hepatic and cardiac dysfunction, were observed with the addition of lintuzumab to induction chemotherapy.

CONCLUSION: The addition of lintuzumab to salvage induction chemotherapy was safe, but did not result in a statistically significant improvement in response rate or survival in patients with refractory/relapsed AML.

Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology, May 18-21, 2002, Orlando, FL.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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