ON SEPTEMBER 13, 2018, moxetumomab pasudotox-tdfk (Lumoxiti), a CD22-directed cytotoxin, was approved for the treatment of adult patients with relapsed or refractory hairy cell leukemia who received at least two prior systemic therapies, including with a purine nucleoside analog.^1,2

Supporting Efficacy Data

APPROVAL WAS BASED on the findings of durable complete response in study 1053 (ClinicalTrials.gov identifier NCT01829711) in patients with histologically confirmed hairy cell leukemia or a hairy cell leukemia variant requiring treatment based on the presence of cytopenias or splenomegaly and who had received prior treatment with at least two systemic therapies, including one purine nucleoside analog.^2,3 Eligible patients had a serum creatinine level ≤ 1.5 mg/dL or creatinine clearance ≥ 60 mL/min estimated by the Cockcroft-Gault equation. A total of 80 patients were enrolled, including 77 with classical hairy cell leukemia and 3 with a hairy cell leukemia variant. Patients received moxetumomab pasudotox-tdfk at 0.04 mg/kg via intravenous (IV) infusion over 30 minutes on days 1, 3, and 5 of each 28-day cycle for a maximum of 6 cycles or until complete response, disease progression, or unacceptable toxicity.

The median age of patients was 60 years (range = 34–84) years, 79% were male, and 94% were white, 98% had an Eastern Cooperative Oncology Group performance status of 0 or 1, and the median number of prior treatments was 3 (range = 2–11). All patients received prior purine nucleoside analog therapy, including 29% in combination with rituximab (Rituxan). The most common other prior treatment regimens were rituximab monotherapy (51%), interferon-alpha (25%), and a BRAF inhibitor (18%). At baseline, 33% had a low hemoglobin level (< 10 g/dL), 68% had neutropenia (< 1,000/mm3), 84% had a platelet count < 100,000/mm3, and 35% had an enlarged spleen (≥ 14 cm).

The major efficacy measure was durable complete response assessed by a blinded independent review committee. A durable complete response was confirmed by maintenance of hematologic remission (hemoglobin ≥ 11 g/dL, neutrophils ≥ 1,500/mm3, and platelets ≥ 100,000/mm3 without transfusions or growth factor for at least 4 weeks) at more than 180 days after independent review committee–assessed complete response. The durable complete response rate was 30% (24 of 80 patients). The overall response rate was 75%, with a complete response in 41% and a partial response in 34%. The median duration of response was not reached.

How It Works

MOXETUMOMAB PASUDOTOX-tdfk is a CD22-directed cytotoxin. The agent binds CD22 on the cell surface of B cells and is internalized, resulting in ADP-ribosylation of elongation factor 2, inhibition of protein synthesis, and apoptotic cell death.

How It Is Used

THE RECOMMENDED DOSE of moxetumomab pasudotox-tdfk is 0.04 mg/kg administered as a 30-minute IV infusion on days 1, 3, and 5 of each 28-day cycle. Treatment should be continued for a maximum of 6 cycles or until disease progression or unacceptable toxicity. Use of this agent is not recommended in patients with severe renal impairment.

Patients should be hydrated with an IV isotonic solution over 2 to 4 hours before and after each infusion and should remain adequately hydrated with daily oral fluids (up to 3 L) on days 1 through 8 of each 28-day cycle. Fluid balance and serum electrolytes should be monitored to avoid fluid overload or electrolyte abnormalities. For thromboprophylaxis, use of low-dose aspirin on days 1 through 8 of each 28-day cycle should be considered, and patients should be monitored for signs and symptoms of thrombosis.

Patients should receive premedication at 30 to 90 minutes prior to each infusion with an antihistamine (eg, hydroxyzine or diphenhydramine), an acetaminophen antipyretic, and a histamine-2 receptor antagonist (eg, ranitidine, famotidine, or cimetidine). If a severe infusion-related reaction occurs, infusion should be interrupted, and appropriate medical management should be instituted. Oral or IV corticosteroid treatment should be given approximately 30 minutes before resuming infusion and before each subsequent infusion. For postinfusion medication, oral antihistamines and antipyretics should be considered for up to 24 hours after infusions and an oral corticosteroid (eg, 4 mg of dexamethasone) is recommended to decrease nausea and vomiting. Adequate oral fluid intake must be maintained.

Product labeling provides detailed instructions on dose modification for and management of capillary leak syndrome, hemolytic uremic syndrome, and increased creatinine.

Safety Profile

AMONG THE 80 patients in study 1053, the most common nonlaboratory adverse events of any grade were infusion- related reactions (50%), peripheral edema (39%), nausea (35%), fatigue (34%), headache (33%), pyrexia (31%), constipation (23%), anemia (21%), and diarrhea (21%). The most common grade 3 or 4 adverse events reactions occurring in at least 5% of patients were hypertension, febrile neutropenia, and hemolytic-uremic syndrome. Overall, fluid retention occurred in 63% of patients. The most common grade 3 or 4 laboratory abnormalities were decreased neutrophils (31%), decreased hemoglobin (15%), decreased platelets (14%), and hypophosphatemia (14%). Adverse events resulted in permanent discontinuation of moxetumomab pasudotox-tdfk in 15% of patients, with the most common cause being hemolytic-uremic syndrome (5%). The most common adverse event resulting in dose delays, omissions, or interruptions was pyrexia (3.8%).

Moxetumomab pasudotox-tdfk has boxed warnings for capillary leak syndrome and hemolytic uremic syndrome, including life-threatening cases. Moxetumomab pasudotox-tdfk also carries warnings/precautions for renal toxicity, infusion-related reactions, and electrolyte abnormalities. Patients should be monitored for changes in renal function prior to each infusion and as clinically indicated. Serum electrolytes should be monitored prior to each dose and on day 8 of each treatment cycle, with mid-cycle monitoring also recommended. Women should not breastfeed when receiving moxetumomab pasudotox-tdfk. ■

REFERENCES

1. U.S. Food and Drug Administration: FDA approves moxetumomab pasudotox-tdfk for hairy cell leukemia. Available at www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm620473.htm. Accessed November 26, 2018.

2. Lumoxiti (moxetumomab pasudotox-tdfk) for injection prescribing information, AstraZeneca Pharmaceuticals LP, September 2018. Available at www. accessdata.fda.gov/drugsatfda_docs/label/2018/761104s000lbl.pdf. Accessed November 26, 2018.

3. Kreitman RJ, Dearden C, Zinzani PL, et al: Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia 32:1768-1777, 2018.