What is teclistamab-cqyv?
Teclistamab-cqyv is a bispecific T-cell engager that binds to the CD3 receptor on the surface of T cells and B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells resulting in T-cell activation, proinflammatory cytokine release, and cellular lysis.
What is teclistamab-cqyv approved for?
Teclistamab-cqyv is approved for adults with relapsed or refractory multiple myeloma who have received at least four lines of prior therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
What is the basis for this approval?
The FDA granted accelerated approval for teclistamab-cqyv based on the results of a single-arm, open-label, multi-center study that evaluated 165 patients who had received at least three prior therapies (N Engl J Med 2022; doi: 10.1056/NEJMoa2203478). The overall response rate was 63 percent (95% CI: 52.1-70.9) with a median follow-up of 14.1 months (0.3-24.4). Median progression-free survival was 11.3 months (95% CI: 8.8-17.1). Median duration of response was 18.4 months (95% CI: 14.9-not estimable). Median time until first response was 1.2 months (range: 0.2-5.5). The FDA approval of teclistamab-cqyv is contingent upon verification of clinical benefit in confirmatory trials.
How do you administer this drug?
Teclistamab-cqyv is administered subcutaneously at the recommended step-up dosing schedule of 0.06 mg/kg on Day 1, 0.3 mg/kg on Day 4, 1.5 mg/kg on Day 7, followed by 1.5 mg/kg weekly thereafter. Patients should be hospitalized for 48 hours after the first three doses of teclistamab-cqyv due to the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
Are there any premedications needed for teclistamab-cqyv?
Patients receiving teclistamab-cqyv should receive premedication prior to step-up dose 1, step-up dose 2, and the first treatment dose to reduce the risk of CRS. Premedication should include a corticosteroid (dexamethasone 16 mg or equivalent), an H1-receptor antagonist (diphenhydramine 50 mg or equivalent), and an antipyretic (acetaminophen 650-1,000 mg or equivalent). Premedication may be required for subsequent doses under certain circumstances.
What are the common side effects associated with teclistamab-cqyv (>=20%)?
Common adverse reactions included pyrexia, CRS, neurotoxicity, musculoskeletal pain, injection site reactions, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, infections, diarrhea, decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, decreased platelets, decreased calcium, decreased albumin, decreased phosphate, decreased sodium, increased gamma-glutamyl transferase, increased alanine aminotransferase, increased alkaline phosphatase, increased aspartate aminotransferase, and increased serum creatinine.
What are the uncommon side effects associated with teclistamab-cqyv (<10%)?
Some uncommon but clinically relevant side effects included febrile neutropenia, sepsis, viral infections, ICANS, Guillain-Barre syndrome, seizures, increased serum bilirubin, and hepatic failure.
Are there any important drug interactions I should be aware of?
No clinical trials have evaluated the drug interaction potential of teclistamab-cqyv. It can cause a release of cytokines that can suppress cytochrome P450 (CYP) enzymes. Monitor for increased toxicity from CYP substrates and consider adjusting the dose of CYP substrates as needed, particularly for 7 days after the first dose and during CRS.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
Dose adjustments are not required for renal or hepatic insufficiency. The effects of severe renal impairment (eGFR <30 mL/min) or moderate to severe hepatic impairment (total bilirubin >1.5x ULN with any AST) on pharmacokinetics of teclistamab-cqyv have not been evaluated.
What should my patients know about teclistamab-cqyv?
* Teclistamab-cqyv is only available through a restricted REMS program because of the risks of CRS and ICANS.
* Antiviral prophylaxis to prevent herpes zoster reactivation should be considered in patients prior to initiation of teclistamab.
* Females of reproductive potential should use effective contraception while on treatment and for 5 months after the last dose due to potential risk to the fetus.
What useful links are available regarding teclistamab-cqyv?
* Prescribing Information: https://bit.ly/3R3Rm2E
* FDA Approval: https://bit.ly/3Hq6u7f
Any ongoing clinical trials related to teclistamab-cqyv?
Teclistamab-cqyv is being studied in patients with newly diagnosed, relapsed/refractory, and smoldering multiple myeloma. There are trials evaluating teclistamab-cqyv use in combination with various anti-myeloma therapies. More information is available at http://clinicaltrials.gov.
CHELSEA MINOR, PHARMD, BCPS, BCOP, is Clinical Pharmacist in Hematology and Bone Marrow Transplant at Washington University School of Medicine in St. Louis. 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.