FDA Approves Loncastuximab Tesirine-lpyl for Relapsed/Refractory Large B-Cell Lymphoma

Diffuse large B-cell lymphoma.

The FDA has granted accelerated approval to loncastuximab tesirine-lpyl (Zynlonta, ADC Therapeutics) for patients with relapsed/refractory large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma, who had two or more lines of systemic therapy.

“Loncastuximab tesirine has shown substantial antitumor activity with a manageable toxicity profile in patients with relapsed/refractory DLBCL who had failed ≥2 prior therapies,” wrote Alexander I. Spira, MD, PhD, FACP, a medical oncologist at Virginia Cancer Specialists, and colleagues, in their publication of results of the ongoing single-arm, open-label phase 2 LOTIS-2 clinical trial (NCT03589469), on which the approval was based. “The treatment was well tolerated by patients.”

LOTIS-2 enrolled 145 patients who had relapsed/refractory DLBCL or high-grade B-cell lymphoma who had previously received at least two systemic therapies. Patients were heavily pretreated, with a median of three prior systemic therapies. The patients received 0.15 mg/kg loncastuximab tesirine-lpyl every three weeks for two cycles, followed by 0.075 mg/kg every three weeks for subsequent cycles. The trial’s primary end point was overall response rate.

Loncastuximab tesirine-lpyl produced an overall response rate of 48.3%, with a complete response rate of 24.1%. After a median follow-up of 7.3 months, the median response duration was 10.3 months.

The most common adverse reactions, including laboratory abnormalities, occurring in at least 20% of patients were thrombocytopenia, increased gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain.

“The overall response rate exceeded the primary end point target for the trial, reinforcing the potential for loncastuximab tesirine to fill a critical unmet need and become a key part of the treatment paradigm for heavily pretreated patients with diffuse large B-cell lymphoma,” concluded Dr. Carmelo Carlo-Stella, MD, PhD, Section Chief of Lymphoid Malignancies and Cancer Therapeutics at Humanitas Clinical and Research Center – IRCCS in Italy, and colleagues in an oral presentation affiliated with the LOTIS-2 study.

The recommended dose of loncastuximab tesirine-lpyl is 0.15 mg/kg every three weeks for two cycles, followed by 0.075 mg/kg every three weeks for subsequent cycles. On Day 1 of each cycle, doses should be given intravenously over a 30-minute period. Starting on the day before receiving loncastuximab tesirine-lpyl, patients should be premedicated with dexamethasone 4 mg orally or intravenously twice a day for three days. 

For More Information

Spira AI, Chen L, Zhou X, et al (2020). Symptoms, health-related quality of life, and tolerability of loncastuximab tesirine in patients with relapsed or refractory diffuse large B cell lymphoma. Blood, 136(suppl_1). DOI:10.1182/blood-2020-139571

Carlo-Stella C, Zinzani PL, Kahl B, et al (2020). Initial results of a phase 2 study of loncastuximab tesirine, a novel pyrrolobenzodiazepine-based antibody-drug conjugate, in patients with relapsed or refractory diffuse large B-cell lymphoma [oral presentation]. European Hematology Association. Abstract S233.

Clinicaltrials.gov (2021). Study to evaluate the efficacy and safety of loncastuximab tesirine in patients with relapsed or refractory diffiuse large B-cell lymphoma (LOTIS-2). NLM identifier: NCT03589469.

Zynlonta (loncastuximab tesirine-lpyl) prescribing information (2021). ADC Therapeutics. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761196s000lbl.pdf

US Food & Drug Administration (2021). FDA grants accelerated approval to loncastuximab tesirine-lpyl for large B-cell lymphoma. Available at: https://www.fda.gov/drugs/fda-grants-accelerated-approval-loncastuximab-tesirine-lpyl-large-b-cell-lymphoma

Image credit: CoRus13. Licensed under CC BY-SA 4.0

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