A Phase I study reports on the safety and potential efficacy of lintuzumab Ac225 plus CLAG-M for relapsed/refractory acute myeloid leukemia.
A study presented at the American Society of Hematology (ASH) 2020 Annual Meeting reported an acceptable safety profile for lintuzumab Ac225 plus CLAG-M, a combination therapy for relapsed/refractory acute myeloid leukemia (AML).
Previous research has shown upfront therapy of lintuzumab Ac225, a radiolabeled anti-CD33 antibody, to be efficacious for unfit AML without significant non-hematological toxicity.
Sameem Abedin, MD, Division of Hematology/Oncology, Medical College of Wisconsin, and colleagues thus conducted the first study to combine radioimmunotherapy with salvage chemotherapy in patients with AML.
The team enrolled medically fit patients (n = 15), all of whom were ≥18 years of age. The median age was 61 years. Further, less than half of the patients received venetoclax/HMA, while more than half had previously received hematopoietic cell transplantation (HCT).
Therapy induction consisted of 300 mcg/d of G-CSF given from days 1-6; 5 mg/m2 of cladribine given from days 2-6; and 10 mg/m2 of mitoxantrone given from days 2-4.
Lintuzumab Ac225 was then administered as a single dose on days 7, 8, or 9. Patients were divided into 3 dosage level cohorts—0.25uCi/kg (Cohort 1, n = 3), 0.50uCi/kg (Cohort 2, n = 9), or 0.75uCi/kg (Cohort 3, n =3).
Reported adverse events were Grade 3 or higher and were irrespective of causality. These included febrile neutropenia (n = 12), infection (n = 8), and maculopapular rash (n = 3). Furthermore, each patient experienced QTc prolongation and tumor lysis syndrome.
Of the 15 patients, 10 experienced a complete remission or complete remission with incomplete count recovery. This total amount remained even after excluding patients who had previously received >3 lines of therapy.
In cohort 1, 1 patient achieved complete remission. As for cohort 2, 3 achieved complete remission, 2 achieved complete remission with incomplete platelet recovery, and 1 achieved complete remission with incomplete count recovery.
And finally, in cohort 3, all 3 patients achieved remission—1 achieved complete remission and 2 achieved complete remission with incomplete platelet recovery.
Of the 10 total with either complete remission or complete remission with incomplete count recovery, 7 achieved minimal residual disease (MRD) negativity by flow.
Abedin and colleagues also reported that all patients who were independent for platelet transfusions pre-treatment recovered platelets.
“Overall, median time to ANC recovery ≥500 was 33 days, and median time to platelet recovery ≥50k was 35 days,” they wrote.
Further, 6 patients proceeded to allogenic HCT following therapy.
Because of the observed acceptable safety at 0.75uCi/kg, the team will proceed with studying a 4th dosage cohort at 1.0uCi/kg.
“Overall, this regimen represents a safe and potentially effective therapy for medically fit RR-AML patients, particularly as a bridge to allogeneic HCT,” they concluded
The study, “A Phase I Study of Lintuzumab Ac225 in Combination with CLAG-M Chemotherapy in Relapsed/Refractory AML,” was presented at ASH 2020.