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Zynlonta First FDA-Approved CD19-Directed Therapy for Large B-Cell Lymphoma

Web Exclusives - FDA Approvals

On April 23, 2021, the FDA accelerated the approval of loncastuximab tesirine-lpyl (Zynlonta; ADC Therapeutics SA), an intravenous, CD19-directed antibody and alkylating agent conjugate, for the treatment of 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, in adults who have received ≥2 lines of systemic therapy.

The FDA granted loncastuximab tesirine an orphan drug designation for this indication. Loncastuximab tesirine is the first and only CD19-targeted antibody–drug conjugate approved as a single-agent treatment for this indication.

“There is a significant unmet need for treatment options for patients with relapsed/refractory DLBCL, including those who have been heavily pretreated and have difficult-to-treat disease. Single-agent Zynlonta demonstrated clinically important outcomes in the pivotal LOTIS-2 study across several disease subtypes,” said Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University. He noted that this included patients who were eligible or ineligible for a transplant, as well as patients who had a transplant.

The FDA approval was based on the LOTIS-2 study, an open-label, single-arm clinical trial of 145 adults with relapsed or refractory DLBCL or high-grade B-cell lymphoma who had received ≥2 systemic regimens. All patients received loncastuximab tesirine 0.15 mg/kg every 3 weeks for 2 cycles, then 0.075 mg/kg every 3 weeks, until disease progression or unacceptable side effects.

The study’s main efficacy outcome was overall response rate (ORR). The ORR was 48.3% (95% confidence interval [CI], 39.9-56.7), including 24.1% complete responses. After a median follow-up of 7.3 months, the median duration of response was 10.3 months (95% CI, 6.9-not evaluable). Of the 70 patients with an objective response, 36% were censored for response duration in the previous 3 months.

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

The prescribing information for loncastuximab tesirine includes warnings regarding the risk for edema, effusions, myelosuppression, infections, and cutaneous reactions. Before administering loncastuximab tesirine, patients should be premedicated with dexamethasone 4 mg orally or intravenously twice daily for 3 days.

Full approval of this indication may be contingent on data from clinical trials to confirm the clinical benefit of the drug.

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Last modified: July 6, 2021
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