On April 23, 2021, 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, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma, after two or more lines of systemic therapy.

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

Approval was based on an open-label, single-arm trial (LOTIS-2; NCT03589469) of 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-lpyl 0.15 mg/kg every three weeks for two cycles, then 0.075 mg/kg every three weeks for subsequent cycles. Patients received the treatment until they experienced disease progression or unacceptable toxicity.

The main efficacy outcome measure was overall response rate (ORR) as assessed by an independent review committee using Lugano 2014 criteria. ORR was 48.3% (95% 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 evaluated). Of the 70 patients who achieved objective responses, 36% were censored for response duration prior to three months.

The most common adverse reactions (≥ 20%), including laboratory abnormalities, were thrombocytopenia, increased gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, increased transaminase, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain. The prescribing information contains warnings and precautions for adverse reactions, including edema and effusions, myelosuppression, infections, and cutaneous reactions.

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

View the full prescribing information for loncastuximab tesirine-lpyl

FDA approved the indication under accelerated approval based on ORR. Continued approval for the indication is contingent on verification and description of clinical benefit in confirmatory trials. 

The review used Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.

FDA granted the application priority review and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics

Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine or device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.  

For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov