FDA Grants Moxetumomab Pasudotox Priority Review for Hairy Cell Leukemia


The FDA has granted a priority review to moxetumomab pasudotox for the treatment of adult patients with hairy cell leukemia who have received at least 2 prior lines of therapy.

The FDA has granted a priority review to moxetumomab pasudotox for the treatment of adult patients with hairy cell leukemia (HCL) who have received at least 2 prior lines of therapy, according to AstraZeneca (MedImmune), the developer of the anti-CD22 recombinant immunotoxin.

The application for moxetumomab pasudotox is based on the phase III 1053 study, which achieved the primary endpoint of durable complete response in adult patients with relapsed/refractory HCL. AstraZeneca noted in a press release that results from the study will be presented at an upcoming medical conference.

Under the priority review program, the FDA acts within 6 months of receiving a supplemental application, rather than the standard 10 months. The FDA is scheduled under the Prescription Drug User Fee Act to make a decision on the moxetumomab pasudotox application by the end of the third quarter of 2018.

According to AstraZeneca, Moxetumomab pasudotox is composed of a binding portion of an anti-CD22 antibody fused to a toxin. After binding to CD22, the molecule is internalized, processed and releases its modified protein toxin that inhibits protein translation, leading to apoptotic cell death.

The phase III 1053 study is a single-arm, multicenter clinical trial assessing the efficacy, safety, immunogenicity, and pharmacokinetics of moxetumomab pasudotox monotherapy. Investigators have recruited 80 patients across 34 sites in 14 countries.

In phase I results published in the journal Blood in February, moxetumomab pasudotox eradicated HCL minimal residual disease (MRD) in >50% of complete responders by bone marrow aspirate (BMA) flow cytometry, the most sensitive measure available.

Twenty-one patients were included in the dose-escalation cohort and 33 were treated with 50 μg/kg of moxetumomab pasudotox in a combined cohort. After 88 cycles of treatment in the dose-escalation cohort, investigators did not observe dose-limiting toxicity or hemolytic uremic syndrome (HUS).

Patients received a median of 2 to 3 prior purine analog courses and 50% to 67% of patients received prior treatment with rituximab (Rituxan).

At the 50 μg/kg dose, the overall response rate (ORR) was 91% with a 71% rate of complete response (CR) in the 21-patient extension cohort. In the combined cohort, the ORR was 88% with a CR of 64%. Investigators detected MRD in 8 (40%) patients by BMA flow cytometry.

The median duration of the 21 CRs was 42.4 months. No patient (n = 7) relapsed after consolidation cycles, while 9 of 14 without consolidation relapsed at a median 13.5 months (range, 4.9-42.4; P = .004).

Of the 20 CRs evaluated for MRD, the median CR duration was 35.3 months. Eleven (55%) patients were MRD-negative and 10 remained in CR at end of study, with median CR duration of 42.2 months (range, 16.3-72.1). Nine (45%) CRs were MRD-positive, with a median CR duration of 13.5 months (range, 4.9-42.4) and 8 relapses (P <.0001).

The median duration of MRD-negative CR had not been reached at the time of the analysis, with 9 of 11 patients remaining MRD-negative for a median of 42.1 months (range, 24.0-69.2).

Four patients died of disease progression after relapsing and going off-study in the combined cohort, including 1 with a best response of MRD-positive CR who developed grade 2 HUS after 5 treatment cycles. Two of the 4 were treated off-protocol with pentostatin-rituximab and 1 each with rituximab and rituximab/bendamustine.

Circulating HCL cells cleared in all 9 patients evaluated for lymphocyte subsets before and after treatment, but normal B cells decreased <50% in 3. Total T cells and CD4+ and CD8+ T-cell subsets increased in all patients except 1 with normal pretreatment and posttreatment CD8 counts. Thus, investigators concluded, anti-CD22 moxetumomab pasudotox spared T cells and, with its short half-life, avoided prolonged B-cell depletion.

Kreitman RJ, Tallman MS, Robak T, et al. Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase I results and long-term follow-up [published online February 27, 2018]. Blood. doi: 10.1182/blood-2017-09-803072.s

Related Videos
Evan Weber, PhD, an assistant professor of pediatrics at Children's Hospital of Philadelphia
Debora Mazzetti, MS, on Multitargeting MicroRNA in Glioblastoma
Francesca Del Bufalo, MD, PhD, a medical doctor and scientist at Bambino Gesù Chidren’s Hospital
Carlos Ramos, MD, on Alternatives to T-Cell Therapy
Omid Hamid, MD
Alexandra Gomez-Arteaga, MD
Pietro Genovese, PhD, the principal investigator at the Gene Therapy Program of Dana-Farber/Boston Children’s Cancer and Blood Disorder Center
Caspian Oliai, MD, MS, the medical director of the UCLA Bone Marrow Transplantation Stem Cell Processing Center
Genovefa (Zenia) Papanicolaou, MD, an infectious diseases specialist at Memorial Sloan Kettering Cancer Center
John DiPersio, MD, PhD, the director of the Center for Gene and Cellular Immunotherapy at Washington University School of Medicine
© 2024 MJH Life Sciences

All rights reserved.