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Moxetumomab pasudotox shows promise in relapsed, refractory hairy cell leukemia
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CHICAGO — The investigational anti-CD22 recombinant immunotoxin, moxetumomab pasudotox, showed a high rate of response and eradicated minimal residual disease among heavily pretreated patients with relapsed/refractory hairy cell leukemia, according to findings from a phase 3 trial presented at the ASCO Annual Meeting.
“Moxetumomab pasudotox had an acceptable tolerability profile and is a nonchemotherapeutic agent that has the potential to become a standard of care for patients with relapsed/refractory hairy cell leukemia,” Robert J. Kreitman, MD, senior investigator at laboratory of molecular biology and head of the clinical immunotherapy section at the NCI, said during his presentation.
Hairy cell leukemia is a highly treatable disease. However, many patients require retreatment after relapse, for whom there is an unmet need for new therapies.
In the multicenter, single-arm, international study, researchers evaluated 40 µg/kg IV moxetumomab pasudotox (MedImmune/AstraZeneca) given on days 1, 3 and 5 of 28-day cycles for up to six cycles in 80 patients (median age, 60 years; 79% men) with relapsed/refractory hairy cell leukemia from 34 centers in 14 countries.
Forty-nine percent of patients had three or more prior lines of therapy and 75% had prior rituximab (Rituxan; Genentech, Biogen).
Durable complete response — defined as complete response with hematologic remission — served as the primary outcome. Secondary outcomes included overall response rate, PFS, safety, immunogenicity and pharmacokinetics.
At a median follow-up of 16.7 months, researchers observed an ORR of 75%, hematologic remission rate of 80%, complete response rate of 41% and durable complete response rate of 30%.
Among 33 patients who achieved a complete response, 82% had immunohistochemistry minimal residual disease-negative status. Eighty-percent of patients achieved hematologic remission, with a median onset of 1.1 months.
Median response duration and median PFS were not reached, Kreitman noted.
The most frequent treatment-related adverse events included nausea (28%), peripheral edema (26%), headache (21%), and pyrexia (20%). Adverse events that led to treatment discontinuation included hemolytic uremic syndrome in 5%, capillary leak syndrome in 3% and increased blood creatinine in 3%.
No treatment-associated deaths occurred. – by Jennifer Southall
Reference:
Kreitman RJ, et al. Abstract 7004. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Kreitman reports receiving patents, royalties or other intellectual property from the NIH/NCI. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Javier Pinilla-Ibarz, MD
The story of this immunotoxin is quite interesting. More than 20 years ago, results of this immunotoxin were published in patients with the orphan disease, harry cell leukemia. The current study reported on 80 patients who achieved a very good response and very long PFS. Certain patients may relapse and may be retreated with the same medication. However, things do change after two relapses, and there is no doubt that there is an unmet need there. Moxetumomab pasudotox will cover this unmet need for patients with multiple relapses.
Another level of interest is that the researchers show that minimal residual negative disease in bone marrow can be achieved, and this is predicted in patients who have long PFS superior to what we would expect with analogues. However, the only caveat is the method they used, immunohistochemistry, has some value in the assessment of minimal residual disease, but it is less sensitive than flow cytometry.
Overall, this is quite an important study that may fill an unmet need for patients with multiple-relapsed disease. Within the past year, we have had targeted therapies that may also have a role for and induce response in these patients with multiple treatment. However, it seems that targeted therapies do not produce such deep levels of response in comparison with the data presented in this study. I would like to congratulate the authors because they have persevered for many years to achieve this outcome found in this trial.
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