Moxetumomab pasudotox for the treatment of relapsed and/or refractory hairy cell leukemia

ABSTRACT

Introduction: Hairy cell leukemia is a rare indolent B-cell malignancy, characterized by pancytopenia, recurrent infections, and splenomegaly. After initial therapy with purine nucleoside analogs, up to 50% of patients relapse after several years of remission. The number of relapsed patients is increasing and, until recently, there was no approved therapy with durable responses for hairy cell leukemia patients in the relapsed setting, thus the need for new non-chemotherapy approach with significant efficacy and less myelosuppression.

Areas covered: Moxetumomab pasudotox is a recombinant immunotoxin containing a Fv fragment of an anti-CD22 monoclonal antibody and truncated Pseudomonas exotoxin (PE38). The authors reviewed pre-clinical and clinical studies that led to the FDA approval of the drug in patients with relapsed and/or refractory hairy cell leukemia, who received at least two prior therapies, including at least one purine nucleoside analog.

Expert opinion: Moxetumomab pasudotox demonstrated a durable complete remission rate of 30% in heavily pretreated patients with hairy cell leukemia, and MRD eradication in 85% of responding patients. Moxetumomab pasudotox got a global FDA approval in September 2018. The US prescribing information carries boxed warnings regarding the risk of capillary leak syndrome and hemolytic uremic syndrome. Long-term follow-up of the pivotal study is ongoing (NCT01829711).

KEYWORDS:

• Hairy cell leukemia
• immunotoxin
• moxetumomab pasudotox

Article highlights

• Hairy cell leukemia is a rare indolent B-cell malignancy characterized by high CD22 expression on the surface of leukemic cells.

• Moxetumomab pasudotox is a recombinant immunotoxin directed against CD22 surface antigen and linked to a truncated Pseudomomas exotoxin A.

• In the pivotal, multicentric, open-label phase 3 trial, moxetumomab resulted in durable complete remission of 30%, and MRD eradication assessed by immunohistochemistry in bone marrows in 85% of responding patients.

• Two unique serious adverse events occurred with the drug, which are hemolytic uremic syndrome and capillary leak syndrome. Although infrequent and reversible, their occurrence may be life-threatening if not recognized and promptly managed.

• FDA approved moxetumomab pasudotox in September 2018 for the treatment of patients with relapsed and/or refractory hairy cell leukemia with at least two prior therapies.

Declaration of interest

F Ravandi has received research funding from BMS and Amgen and advisory board member for BMS, and Ariad, and Amgen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

A peer reviewer on this manuscript has received research grants from Medimmune and Astra Zeneca. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.