What is idecabtagene vicleucel?
Idecabtagene vicleucel is a chimeric antigen receptor (CAR)-positive T-cell therapy targeting B-cell maturation antigen (BCMA). The CAR construct includes an anti-BCMA scFv-targeting domain for antigen specificity, a transmembrane domain, a CD3-zeta T-cell activation domain, and a 4-1BB costimulatory domain.
How does idecabtagene vicleucel work?
BCMA is expressed on the surface of normal and malignant plasma cells. Antigen-specific activation of idecabtagene vicleucel results in CAR-positive T-cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.
What is this approved for?
Idecabtagene vicleucel was granted approval by the FDA for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
What is the basis for this approval?
Idecabtagene vicleucel was studied in a multicenter, open-label, single-group, Phase II study designed to evaluate efficacy in patients with advanced and heavily pretreated multiple myeloma. Patients were assigned to receive idecabtagene vicleucel target doses of 150 x 106 to 450 x 106 CAR-positive T cells. After a median follow-up of over 13 months, the overall response rate was 73 percent for patients, including a 33 percent complete response (CR) or stringent complete response (sCR). The median progression-free survival was 8.8 months in the overall patient population and 20.2 months in patients achieving a CR/sCR. Median overall survival was 19.4 months. Adverse reactions were common, though rates of high-grade (grade >=3) cytokine release syndrome (CRS) and neurotoxicity were low at 5 percent and 3 percent, respectively (N Engl J Med 2021; doi: 10.1056/NEJMoa2024850).
How do you administer this drug?
Idecabtagene vicleucel is administered as a single-dose infusion given on Day 0 following lymphodepletion with fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2 daily for 3 days (D-5 to D-3).
Are there any pre-medications needed?
Idecabtagene vicleucel has low emetic risk and does not require antiemetic medications. Premedication with acetaminophen and diphenhydramine are recommended approximately 30-60 minutes before infusion of idecabtagene vicleucel. Prophylactic use of dexamethasone or other systemic corticosteroids should be avoided.
What are the common side effects associated with idecabtagene vicleucel (> or =20%)?
The most common adverse events were cytopenias (neutropenia, anemia, thrombocytopenia, lymphopenia) following lymphodepletion chemotherapy, infection (all grade neutropenia: 91%; grade 3 or 4: 89%), gastrointestinal adverse events (diarrhea, nausea), and laboratory abnormalities. All-grade CRS was common (84%), though incidence of high-grade (according to Lee et al. 2014 criteria) CRS and neurotoxicity were low.
What are the uncommon side effects associated with idecabtagene vicleucel (less than 20%)?
Coagulopathy, cardiac disorders, gastrointestinal hemorrhage, hemophagocytic lymphohistiocytosis, fungal infections, psychiatric disorders, respiratory, and thrombosis occurred in <10 percent of patients treated with idecabtagene vicleucel.
Are there any important drug interactions I should be aware of?
No known clinically significant drug interactions exist.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
Hepatic and renal impairment studies were not conducted, and there are no dosage adjustments per the prescribing information. However, dose adjustments for cyclophosphamide and fludarabine may be necessary.
What should my patients know about idecabtagene vicleucel?
* Manufacture and shipment of product may take 4 weeks or longer following blood collection (apheresis).
* Idecabtagene vicleucel may cause side effects that are severe or life-threatening. Patients should notify their provider if they have difficulty breathing, fever, confusion, dizziness, word-finding difficulties, or other unusual side effects following infusion.
* Patients should not drive or operate machinery for at least 8 weeks following infusion.
* Patients should plan to stay within 2 hours of the health care facility where CAR T cell was received for at least 4 weeks after infusion.
* Treatment can lower one or more types of blood cells, which can make patients feel weak or tired or increase risk of infection or bleeding.
* Patients will be provided with a Patient Wallet Card and instructed to remain within 2 hours of the certified health care facility for at least 4 weeks following infusion.
What else should I know about idecabtagene vicleucel?
All relevant staff involved in prescribing, dispensing, or administering idecabtagene vicleucel are required to be enrolled in the REMS program and adhere to the REMS requirements, including availability of tocilizumab on-site for immediate administration.
What useful links are available regarding idecabtagene vicleucel?
* New England Journal of Medicine Research: https://bit.ly/2RiFHCh
* FDA Approval: https://bwnews.pr/3nT1WLh
* Patient Information: https://www.abecma.com/
* Risk Evaluation and Mitigation Strategy: https://www.abecmarems.com/
Any ongoing clinical trials related to idecabtagene vicleucel?
Idecabtagene vicleucel is being investigated in various ongoing trials for treatment of multiple myeloma and other B-cell lymphomas. More information is available about these trials at clinicaltrials.gov.
ADAM ROBINSON, PHARMD, is PGY2 Oncology Pharmacy Resident at Barnes-Jewish Hospital, St. Louis, Mo. JANELLE E. MANN, PHARMD, BCOP, is Clinical Oncology Pharmacist/ Manager, Clinical Pharmacy Services at Washington University School of Medicine, St. Louis, Mo. 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.