FDA Approves Moxetumomab Pasudotox for Hairy Cell Leukemia

Richard Pazdur, MD

The FDA has approved the CD22-directed recombinant immunotoxin moxetumomab pasudotox (Lumoxiti) for the treatment of adult patients with relapsed or refractory hairy cell leukemia (HCL) who have received at least 2 prior lines of therapy, including treatment with a purine nucleoside analog.

The approval was based on findings from single-arm, open-label study that included 80 patients with HCL, wherein moxetumomab pasudotox induced a complete remission (CR) lasting for over 180 days (durable CR) for 30% of patients. The objective response rate (ORR) was 75%. The agent was approved with a Boxed Warning regarding the potential for grade 3/4 capillary leak syndrome (CLS) and hemolytic uremic syndrome (HUS), which occurred in 2.5% and 5% of patients, respectively.

“Lumoxiti fills an unmet need for patients with hairy cell leukemia whose disease has progressed after trying other FDA-approved therapies,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “This therapy is the result of important research conducted by the National Cancer Institute that led to the development and clinical trials of this new type of treatment for patients with this rare blood cancer.”

The phase III study enrolled patients across 34 centers in 14 countries. Moxetumomab pasudotox was administered at 40 µg/kg intravenously on days 1, 3, and 5 of each 28-day cycle. Overall, 50 patients completed a full 6 cycles of treatment (62.5%), with patients most commonly discontinuing due to CR with minimal residual disease (MRD) negativity (15%) and adverse events (15%).

The median age of patients enrolled in the study was 60 years, with 6% having a prior splenectomy and 4% having an HCL variant. The median blood counts were 11.10 g/dL, 0.81 x 10³ per µL, and 68 x 10³ per µL for hemoglobin, neutrophils, and platelets, respectively. Eighty-five percent of patients had HCL involvement in the bone. The median number of prior lines of therapy was 3 (range, 2-11), with 75% of patients had received prior rituximab (Rituxan) and 18% had received a BRAF inhibitor.

By independent review, out of the 75% ORR, 41% of patients had a CR as their best response, with 35% of patients having a CR with MRD negativity. The partial response rate was 34% and 15% of patients had stable disease. By investigator assessed criteria, the durable CR rate was 48%, with 51% of patients having a CR as their best response. The MRD-negative CR rate was 33% and the ORR was 79%.

At 16.7 months’ median follow-up, the median duration of CR had not yet been reached, nor had median progression-free survival. In a 12-month landmark analysis, 92% of patients who achieved a CR (n = 33) remained in remission with a CR. All patients who achieved an MRD-negative CR (N = 27) remained in remission at 6 months and 79% continued to test negative for MRD at 12 months (95% CI, 51%-92%).

A treatment-related adverse event (TRAE) of any grade was experienced by 90% of patients treated with moxetumomab pasudotox. The most common TRAEs were nausea (27.5%), peripheral edema (26.3%), headache (21.3%), and pyrexia (20%). Grade 3/4 TRAEs occurred in 30% of patients, with the most common events being lymphocyte count decrease (7.5%), HUS (5%), and CLS (2.5%). CLS and/or HUS developed during any treatment cycle for the 10 patients with these events and all resolved with supportive care and/or treatment discontinuation.

“With very few treatments available, there remains significant unmet medical need for people with relapsed or refractory disease," senior investigator Robert J. Kreitman, MD, head of Clinical Immunotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, said in a statement when the findings were presented. "The response rates observed in this trial, and elimination of the residual leukemia cells that cause relapse in some patients, highlight the potential impact this potential new medicine could have on patients and the management of this disease.”

The approval for moxetumomab pasudotox was granted under the FDA's priority review and fast track designations. Additionally, the medication was granted an orphan drug designation.

Kreitman RJ, Dearden C, Zinzani PL, et al. Moxetumomab pasudotox in heavily pretreated patients with relapsed/refractory hairy cell leukemia: Results of a pivotal international study. J Clin Oncol. 2018;36 (suppl; abstr 7004).