Moxetumomab pasudotox for the treatment of hairy cell leukemia

ABSTRACT

Introduction: Cladribine and pentostatin are the drugs of choice in the treatment of hairy cell leukemia (HCL). Recently, immunotoxin moxetumomab pasudotox has been introduced to improve the prognosis in relapsed and refractory HCL.

Areas covered: This review discusses the mechanism of action, safety, and efficacy of moxetumomab pasudotox in HCL patients. A literature review of the MEDLINE database for articles in English concerning immunotoxins, moxetumomab pasudotox, and hairy cell leukemia was conducted via PubMed. Publications from 2000 through December 2018 were scrutinized. The search terms used were immunotoxins and moxetumomab pasudotox in conjunction with hairy cell leukemia. Conference proceedings from the previous five years of the American Society of Hematology, European Hematology Association and American Society of Clinical Oncology were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles.

Results/conclusion: Moxetumomab pasudotox, a novel recombinant anti-CD22 immunotoxin, was well tolerated and active in the previous phase 1 and 3 studies in patients with HCL. The drug has been approved in 2018 by the FDA for the treatment of patients with relapsed/refractory HCL who had at least two prior systemic therapies including at least one purine nucleoside analog.

Expert opinion: The use of moxetumomab pasudotox is a promising new strategy for the treatment of HCL.

KEYWORDS:

• Anti-CD22 antibody
• CAT-8015
• cladribine
• hairy cell leukemia
• HCL variant
• immunotoxin
• moxetumomab pasudotox
• pentostatin
• refractory
• relapsed
• rituximab

Article Highlights

• Hairy cell leukemia is a rare and indolent form of small, mature, B-cell leukemia.

• Purine analogs, pentostatin, and cladribine are currently the drugs of choice in the treatment of HCL

• Despite very high response rates following purine analog treatment, about 50% of the patients ultimately relapse or have refractory disease after responding to initial treatment. For these patients, novel therapies are needed.

• Over the last few years, several new drugs, particularly immunotoxins and BRAF inhibitors, have been developed and investigated in relapsed and refractory HCL.

• Moxetumomab pasudotox is a new generation of CD22-specific immunotoxins composed of the Fv fragment of an anti-CD22 monoclonal antibody fused to a 38 kDa fragment of Pseudomonas exotoxin.

• Moxetumomab pasudotox is highly active in relapsed/refractory HCL and may have a role in the treatment of patients in whom conventional therapies produce limited responses or treatment failure.

• In a single-group phase 3 study involving 80 HCL patients who had relapsed after at least two previous systemic therapies, the OR rate was 75%, including 41% CR; 30% had a CR that lasted more than 180 days.

• Moxetumomab pasudotox eradicates HCL minimal residual disease (MRD) in more than 50% of the patients achieving CRs, and MRD negativity is associated with prolonged CR duration.

• Common adverse events in patients treated with moxetumomab pasudotox include edema, nausea, fatigue, headache, fever, constipation, diarrhea, and anemia.

• A boxed warning in prescribing information includes the risk of developing capillary leak syndrome and hemolytic uremic syndrome, which can result in life-threatening kidney failure.

• The FDA has approved moxetumomab pasudotox (Lumoxiti) for patients with HCL who have received at least two prior systemic therapies, including a purine nucleoside analog.

Acknowledgments

We thank Edward Lowczowski from the Medical University of Lodz, Poland for editorial assistance.

Declaration of interest

A Janus and T Robak have received a research grant from Medimmune and Astra Zeneca. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

The study was supported in part by grant funding from the Medical University of Lodz, Poland: No. 503/1-093-01/503-11-004 and by the Foundation for the Development of Diagnostics and Therapy, Warsaw, Poland.