Loncastuximab tesirine receives FDA approval for the treatment of large B-cell lymphoma

On 23 April 2021, FDA (the US Food and Drug Administration) granted accelerated approval to loncastuximab tesirine-lpyl (Zynlonta, ADC Therapeutics SA), a CD19-targeted antibody and alkylating-agent conjugate, for relapsed or treatment-resistant large B-cell lymphoma (LBCL) after at least 2 prior lines of therapy. This includes diffuse large B-cell lymphoma (DLBCL) not otherwise specified, arising from low-grade lymphoma, and high-grade B-cell lymphoma.

• Related topic: What is lymphoma, or lymphatic cancer? What are its symptoms and treatments?

FDA approval based on the LOTIS-2 study

The approval was based on LOTIS-2 (NCT03589469), an open-label, single-arm study in 145 adults with high-grade B-cell lymphoma or relapsed or refractory DLBCL after at least two prior systemic regimens. Patients received loncastuximab tesirine-lpyl at 0.15 mg/kg every 3 weeks for 2 cycles, followed by 0.075 mg/kg every 3 weeks for subsequent cycles. Patients continued treatment until progressive disease or unacceptable toxicity.

Results

The main efficacy outcome measure in LOTIS-2, assessed by an independent review committee using the Lugano 2014 criteria, was the overall response rate.

• The overall response rate was 48%, including 24.1% complete responses.
• After a median follow-up of 7.3 months, the median duration of response was 10.3 months
• Of the 70 patients with an objective response, 36% maintained their response for at least 3 months.

Side effects

The most common adverse reactions, including laboratory abnormalities, in patients receiving loncastuximab tesirine-lpyl were thrombocytopenia, increased gamma-glutamyltransferase (GGT), neutropenia, anemia, hyperglycemia, increased transaminases, fatigue, hypoalbuminemia, rash, edema, nausea and muscle pain. The prescribing information provides warnings and precautions for adverse reactions including edema and effusions, myelosuppression, infections and skin reactions.

Recommended dose of loncastuximab tesirine

The recommended dose of loncastuximab tesirine-lpyl is 0.15 mg/kg every 3 weeks for 2 cycles, followed by 0.0075 mg/kg every 3 weeks for subsequent cycles, administered by intravenous infusion over 30 minutes on the first day of each cycle. Patients should receive 4 mg of oral or intravenous dexamethasone twice daily for 3 days, starting the day before loncastuximab tesirine-lpyl.

This indication is approved under accelerated approval based on the overall response rate. Continued approval for this indication may be contingent on verification and description of clinical benefit in a confirmatory trial or trials.

Healthcare professionals should report all serious adverse events suspected to be associated with the medicine through the FDA MedWatch Reporting System or by calling.

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