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FDA Grants Accelerated Approval to Loncastuximab Tesirine-lpyl for Large B-Cell Lymphoma


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On April 23, the U.S. Food and Drug Administration (FDA) granted accelerated approval to loncastuximab tesirine-lpyl (Zynlonta), a CD19-directed antibody and alkylating agent conjugate, for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma.

LOTIS-2

Approval was based on LOTIS-2 (ClinicalTrials.gov identifier NCT03589469), an open-label, single-arm trial in 145 adult patients with relapsed or refractory DLBCL or high-grade B-cell lymphoma after at least two prior systemic regimens. Patients received loncastuximab tesirine at 0.15 mg/kg every 3 weeks for two cycles, then at 0.075 mg/kg every 3 weeks for subsequent cycles. Patients received treatment until progressive disease or unacceptable toxicity.

The main efficacy outcome measure was overall response rate as assessed by an independent review committee using Lugano 2014 criteria.

The overall response rate was 48.3% (95% confidence interval [CI] = 39.9%–56.7%) with a complete response rate of 24.1% (95% CI = 17.4%–31.9%). After a median follow-up of 7.3 months, median response duration was 10.3 months (95% CI = 6.9–not evaluable). Of the 70 patients who achieved objective responses, 36% were censored for response duration prior to 3 months.

The most common (≥ 20%) adverse reactions in patients receiving loncastuximab tesirine, including laboratory abnormalities, were thrombocytopenia, increased gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain.

The prescribing information provides warnings and precautions for adverse reactions, including edema and effusions, myelosuppression, infections, and cutaneous reactions.

The recommended loncastuximab tesirine dosage is 0.15 mg/kg every 3 weeks for two cycles, then 0.075 mg/kg every 3 weeks for subsequent cycles, by intravenous infusion over 30 minutes on day 1 of each cycle (every 3 weeks). Patients should be premedicated with dexamethasone at 4 mg orally or intravenously twice daily for 3 days beginning the day before loncastuximab tesirine.


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