SAN DIEGO, CA—Combination therapy of lintuzumab and low-dose cytarabine did not improve overall survival (OS) in older patients with untreated acute myeloid leukemia (AML) when compared with placebo and low-dose cytarabine, according to study results presented at the American Society of Hematology’s 53rd Annual Meeting and Exposition.

In previous studies, lintuzumab, a humanized antibody directed to CD33, has demonstrated modest activity as monotherapy in myeloid malignancies. Jeffrey E. Lancet, MD from the Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, and colleagues conducted a randomized, placebo-controlled, double-blinded, Phase 2b study of lintuzumab to determine if its addition to low-dose cytarabine could improve overall survival (OS) in older patients (>60 years) with AML.

Treatment-naive patients with centrally confirmed AML and a minimum blast percentage of 20% with ≥50% CD33 expression were enrolled in the study. The maximum allowed white blood cell count (WBC) at baseline was 30,000/μL. For the intent-to-treat population, patient demographics were well balanced between the two groups, with a median age of 70 years (range 60–90), 53% female. At baseline, 74% of patients had blast percentages ≥30% and 23% had a history of antecedent hematological disorder. A median of 95% CD33 expression was recorded in either bone marrow or peripheral blood. Intensive induction chemotherapy was declined by all patients. 

Patients were given lintuzumab 600mg (n=107) or placebo (n=104) on Days 1, 8, 15, and 22 of Cycle 1 and on Days 1 and 15 of subsequent cycles. All patients received cytarabine 20mg subcutaneously twice daily on Days 1–10 of each 28-day cycle. A maximum of 12 cycles of therapy were administered. Patients were followed every six weeks until death or study completion. OS was determined using an unstratified log rank test. Secondary endpoints included transfusion requirements (platelet and RBC), infections or fevers requiring hospitalizations or IV antibiotics, and complete blood cell counts.

Of the 211 patients enrolled, 24 were alive at the time of analysis (maximum follow-up 32 months). The estimated median OS of lintuzumab vs placebo was 4.7 months vs 5.1 months (HR 0.956; P=0.7585, 95% CI: 0.72–1.28). The median OS across both treatment groups was 5.0 months and was significantly impacted by cytogenetic risk (8.7 months for standard-risk vs. 4.5 months for high-risk; HR 1.63 [95% CI: 1.19–2.25], P=0.0024). Age and history of antecedent hematologic disorder were not significant predictors of OS.

Secondary outcome measures showed that rates of infections or fevers of unknown origin requiring hospitalization or IV antibiotics did not differ between study arms. Overall, 28% of patients were observed to have no peripheral blasts, ANC >1×109/L, platelets >100×109/L, and no transfusions for at least one week. The rate of adverse events did not differ between the treatment arms, with the exception of infusion-related reactions (primarily Grade 1), which occurred more frequently in the lintuzumab group (51% vs 7% with placebo).

Dr. Lancet states, “While lintuzumab was not effective, CD33 remains a compelling target for AML because it is widely expressed by malignant cells and appears to be absent from pluripotent hematopoietic stem cells.” Investigators concluded that similar results were observed in the high-risk cytogenics subgroup, confirming low-dose cytarabine as a valid comparator in trials of older patients with AML.