On 23 April 2021, the US Food and Drug Administration (FDA) granted accelerated approval to loncastuximab tesirine-lpyl (Zynlonta, ADC Therapeutics SA), 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. <\/p>\n
Approval was based on LOTIS-2 (NCT03589469), an open-label, single-arm study 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-lpyl 0.15 mg\/kg every 3 weeks for 2 cycles, then 0.075 mg\/kg every 3 weeks for subsequent cycles. Patients received treatment until progressive disease or unacceptable toxicity. <\/p>\n
The main efficacy outcome measure was overall response rate (ORR), as assessed by an independent review committee using Lugano 2014 criteria. The ORR 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). <\/p>\n
After a median follow-up of 7.3 months, median response duration was 10.3 months (95% CI 6.9, NE). Of the 70 patients who achieved objective responses, 36% were censored for response duration prior to 3 months. <\/p>\n
Most common (\u226520%) adverse reactions in patients receiving loncastuximab tesirine-lpyl, including laboratory abnormalities, are thrombocytopenia, increased gamma-glutamyltransferase, neutropenia, anaemia, hyperglycaemia, transaminase elevation, fatigue, hypoalbuminemia, rash, oedema, nausea, and musculoskeletal pain. <\/p>\n
The prescribing information provides warnings and precautions for adverse reactions including oedema and effusions, myelosuppression, infections, and cutaneous reactions. <\/p>\n
The recommended loncastuximab tesirine-lpyl dosage is 0.15 mg\/kg every 3 weeks for 2 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 4 mg orally or intravenously twice daily for 3 days beginning the day before loncastuximab tesirine-lpyl. <\/p>\n
Full prescribing information for Zynlonta is available here<\/a>. <\/p>\n This indication is approved under accelerated approval based on ORR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). <\/p>\n This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA\u2019s assessment. <\/p>\n This application was granted priority review and orphan drug designation. <\/p>\n Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA\u2019s MedWatch Reporting System. <\/p>\n For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA\u2019s Oncology Center of Excellence<\/a> Project Facilitate<\/a>.<\/p>\n