Hairy cell leukemia (HCL) is a rare B cell malignancy characterized by high CD22 expression. As the number of leukemia cells increases, fewer healthy white blood cells, red blood cells, and platelets are produced. Accumulation of neoplastic cells typically results in splenomegaly; a variable reduction in the production of normal red blood cells, platelets, mature granulocytes, and monocytes; and complications of anemia, bleeding, and infection. Moxetumomab pasudotox-tdfk is a CD22-directed cytotoxin, that binds CD22 on the cell surface of B-cells and is internalized. Moxetumomab pasudotox-tdfk internalization results in ADP-ribosylation of elongation factor 2, inhibition of protein synthesis, and apoptotic cell death.
Moxetumomab pasudotox-tdfk (Lumoxiti™) a first-in-class treatment approved by the US Food and Drug Administration (FDA) for hairy cell leukemia. Prior to its approval, treatment options consisted of Purine analogs (i.e., cladribine or pentostatin), splenectomy or interferon for hairy cell leukemia. Variant hairy cell leukemia — HCL variant (HCL-v) is poorly responsive or resistant to standard treatment (i.e., splenectomy, interferon, purine analogs). Although treatment data are sparse, individuals with HCL-v were candidates for treatment with monoclonal antibodies (e.g., rituximab, alemtuzumab).
PEER-REVIEWED LITERATURE
SUMMARY
The study of Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia (HCL) was a phase III, multicenter, single-arm study of moxetumomab pasudotox in individuals with relapsed/refractory hairy cell leukemia. Between 2013 and 2018, 77 individuals with HCL were enrolled to participate. Moxetumomab pasudotox-tdfk (Lumoxiti™) was infused intravenously on days 1, 3 and 5 of each 28 day cycle for a maximum of 6 cycles or until disease progression, unacceptable toxicity occurs, the subject begins alternate therapy, or documented CR (for subjects who have no assessable minimal residual disease [MRD] and not to exceed 6 cycles). Primary outcome measures were to determine percentage of participants with Durable Complete responce (CR) at the end of the treatment (EOT) up to 24 weeks and post (EOT) Day 181. In the study, 50 percent of individuals received three or more prior courses of purine nucleoside analogs and 75 percent received prior rituximab.
Durable CR was defined as overall response that meets blood, bone marrow and imaging criteria for complete response (CR), followed by a >180 day duration of hematologic remission (HR).
Responses were seen in 60 individuals (75 percent) overall with 33 individuals (41 percent) achieving a CR and 27 individuals (34 percent) achieving MRD negativity. Of these, 24 individuals (30 percent) maintained hematologic remission for more than 180 days. MRD negativity was associated with prolonged CR. None of the three individuals with HCL-variant achieved CR.
OFF-LABEL INDICATION
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