Moxetumomab Pasudotox: An Alternative to Chemotherapy in Relapsed/Refractory Hairy Cell Leukemia

In a pivotal phase III clinical trial of moxetumomab pasudotox in patients with relapsed/refractory hairy cell leukemia (HCL), three-quarters of participants responded to treatment. Forty-one percent of those were complete responses (CRs), and many complete responders also had undetectable levels of minimal residual disease (MRD), according to lead author Robert J. Kreitman, MD.

“Moxetumomab pasudotox is a non-chemotherapeutic agent that has the potential to become a standard of care for patients with relapsed/refractory HCL,” Dr. Kreitman, of the National Cancer Institute’s Center for Cancer Research, said during his presentation of the results at the 2018 ASCO Annual Meeting.

The trial included 80 patients (median age = 60 years; range = 34-84 years) who had received at least two prior systemic therapies, including at least one purine nucleoside analog. Participants were excluded if they had poor hepatic, renal, or pulmonary function; received therapy within three weeks of enrollment; or previously received an immunotoxin.

The median number of prior systemic therapies was three (range = 2-11), and 39 patients (49%) received at least four prior lines of therapy. “This was a heavily pretreated population, and the HCL involvement in bone marrow was high, at a median of 85 percent [range = 0-100%],” Dr. Kreitman noted.

Moxetumomab pasudotox 40 µg/kg was administered intravenously on days 1, 3, and 5 of 28-day cycles, for up to six cycles. Participants were treated until disease progression or unacceptable toxicity. If patients were found to have MRD–negative status within six cycles of treatment, they had the option to discontinue.

The study’s primary endpoint was durable CR followed by hematologic remission (defined as resolution of cytopenias without transfusions or growth factors) that lasted for longer than 180 days.

As of May 24, 2017 (data cutoff), 50 participants (62.5%) had completed six cycles of treatment and were still being followed.

Of the 30 remaining patients, reasons for treatment discontinuation included: MRD-negativity within six cycles (n=12; 15%), adverse events (AEs; n=12; 15%), lack of benefit (n=3; 3.8%), disease progression (n=2; 2.5%), and death (n=1; 1.3%).

At a median follow-up of 16.7 months (range not provided), the ORR was 75 percent, including:

  • 64 patients with hematologic remission (80%)
  • 33 patients with CR (41%)
  • 24 patients with CR lasting >180 days (30%)

In his presentation, Dr. Kreitman focused on the nine patients who achieved CR, but not a lasting hematologic remission: “Two patients had relapsed disease during the six-month follow-up period, five had CR onset later than the end of treatment that wasn’t captured by the reviewer, and two patients withdrew consent,” he reported.

Dr. Kreitman noted that the 64 patients who achieved hematologic remission did so rapidly, at a median of 1.1 months (range not reported). The duration of both objective response and median progression-free survival were not reached.

As suggested by the 15 patients who discontinued treatment after achieving MRD-negativity early, treatment with moxetumomab pasudotox was associated with clearance of HCL burden: Twenty-seven of the 33 (82%) patients in CR also had undetectable MRD.

The most common treatment-related AEs included: nausea (28%), peripheral edema (26%), headache (21%), and pyrexia (20%). Treatment-related AEs that led to moxetumomab pasudotox discontinuation were hemolytic uremic syndrome (n=4; 5%), capillary leak syndrome (n=2; 3%), and increased blood creatinine (n=2; 3%). Both hemolytic uremic syndrome and capillary leak syndrome were “manageable and reversible with close monitoring and best supportive care,” the authors reported.

Three patients died during study follow-up, but none of the deaths were considered related to treatment.

Based on results from the phase I trial, the U.S. Food and Drug Administration granted moxetumomab pasudotox priority review for the treatment of adults with HCL who have received at least two prior lines of therapy in April 2018.

The findings of this trial are limited by its single-arm design and small patient population.

The authors report financial relationships with AstraZeneca and MedImmune, the manufacturer of moxetumomab pasudotox.


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. Abstract #7004. Presented at the 2018 ASCO Annual Meeting, June 2, 2018; Chicago, IL.