What is loncastuximab tesirine-lpyl?
Loncastuximab tesirine-lpyl is an antibody-drug conjugate for adults with refractory or relapsed large B-cell lymphoma. It consists of a CD19 monoclonal antibody, a pyrrolobenzodiazepine dimer cytotoxic alkylating agent (SG3199), and a protease-cleavable linker.
Loncastuximab tesirine-lpyl binds to CD19 on the surface of B cells through its CD-19 monoclonal antibody and is internalized and followed by the release of SG3199 via proteolytic cleavage of the linker. SG3199 induces cell death through binding to DNA and forming highly cytotoxic DNA interstrand crosslinks.
Loncastuximab tesirine-lpyl was granted accelerated approval based on overall response rates for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of therapy.
It was approved based on the overall response rates seen in a Phase II open-label, single-arm study in adults with relapsed/refractory DLBCL, including double-hit and triple-hit DLBCL, as well as primary mediastinal B-cell lymphoma. Patients with bulky disease or active central nervous system lymphoma were excluded. A total of 184 patients were assessed for eligibility and 145 were enrolled and received at least one dose of the drug. Loncastuximab was administered at 0.15 mg/kg on Day 1 of a 3-week cycle for the first 2 cycles, followed by 0.075 mg/kg every 3 weeks for subsequent cycles. The primary endpoint included overall response rate (ORR), including best overall response of complete response (CR) or partial response (PR). Additional endpoints of interest included duration of response (DOR), relapse-free survival (RFS), and progression-free survival (PFS).
ORR was 48.3 percent (95% CI: 39.9,56.7) with 35 (24%) in CR and 35 (24%) in PR. Median DOR was 10.3 months (95% CI: 6.9, not estimable) with a median PFS of 4.9 months (95% CI: 2.9-8.3). Median RFS was 13.4 months (Lancet Oncol 2021; https://doi.org/10.1016/S1470-2045(21)00139-X).
How do you administer this drug?
Loncastuximab tesirine-lpyl is given intravenously over 30 minutes on Day 1 of each cycle, repeated every 3 weeks. It is dosed at 0.15 mg/kg on Day 1 for the first 2 cycles, followed by 0.075 mg/kg for subsequent cycles.
Are there any premedications needed?
Dexamethasone 4 mg given twice daily for 3 days starting the day before loncastuximab infusion is recommended. If not started the day before, dexamethasone should be administered at least 2 hours prior.
What are common side effects (> or =10%)?
* Hematologic: anemia, thrombocytopenia, neutropenia, leukopenia
* Chemistry: gamma-glutamyltransferase and transaminase elevation, hyperglycemia, hypoalbuminemia
* GI: abdominal pain, constipation, diarrhea, nausea, vomiting
* General: fatigue, erythema, edema (including face, generalized, peripheral, ascites, fluid overload, and swelling), decreased appetite
* Dermatologic: pruritus, rash, photosensitivity
* Respiratory: dyspnea, pleural effusion
* Musculoskeletal: pain
* Infection: upper respiratory tract infection
What are uncommon side effects (< 10%)?
Additional side effects include pneumonia (5%), hyperpigmentation (4%), febrile neutropenia (3%), pericardial effusion (3%), sepsis (2%), and infusion site extravasation (<1%).
Are there any important drug interactions?
SG3199 in loncastuximab tesirine-lpyl is metabolized by CYP3A4/5 in vitro; however, there are no recommended adjustments for drug interactions. Use caution with any additional myelosuppressive agents.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
There are no renal or hepatic dose adjustments for loncastuximab tesirine-lpyl, but it has not been studied in severe renal (CrCL <30 mL/min) or moderate-severe hepatic dysfunction.
Practical tips
* Ensure platelets are above 50,000 or higher and absolute neutrophil count is 1,000 or higher prior to each dose of loncastuximab tesirine-lpyl.
* Hold and monitor counts until resolution. If dosing is delayed longer than 3 weeks, reduce subsequent doses by 50 percent. If toxicity recurs, consider discontinuation.
* For patients with a BMI >35 kg/m2, the dose is calculated on an adjusted body weight using the following calculation:
* ABW in kg = 35 kg/m2 x (height in meters)2
What should my patients know about loncastuximab tesirine-lpyl?
Patients should contact their health care provider if they experience any of the following:
* Shortness of breath, swelling, weight gain, or difficulty breathing
* Fever of 100.4 or higher, chills, weakness
* Bleeding or bruising
* Avoid contact with sunlight and utilize protective clothing and sunscreen products
What else should I know about this drug?
Adjusted body weight dosing for a BMI >35 kg/m2 is required due to cumulative toxicity seen in the Phase I study. Serious infections have occurred in patients treated with loncastuximab tesirine-lpyl. Monitor closely and consider growth factor support for patients with myelosuppression.
What useful links are available?
* FDA Accelerated Approval: https://bit.ly/3U68Rzz
* Prescribing Information: https://bit.ly/3zph5uE
Any ongoing clinical trials for this drug?
Clinical trials with loncastuximab tesirine-lpyl are being conducted to investigate its place in therapy for the treatment of relapsed/refractory lymphoma, including DLBCL and mantle cell lymphoma. It is being evaluated as consolidation therapy post-stem cell transplant or CAR T-cell therapy, and with agents such as rituximab, venetoclax, or ibrutinib.
KENDALL C. SHULTES, PHARMD, BCOP, is Clinical Pharmacist Practitioner at the VA Tennessee Valley Healthcare System in Nashville. JANELLE E. MANN, PHARMD, BCOP, is Clinical Oncology Pharmacist/Manager, Clinical Pharmacy Services at Washington University School of Medicine. She serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, serves as the Pharmacy Forum column physician advisor.