Because of CRS and neurologic toxicity risk, the therapy is available through a REMS program.
Teclistamab-cqyv (Techvayli; Johnson & Johnson) has received accelerated approval from the FDA for the treatment of adult patients with relapsed/refractory (R/R) multiple myeloma (MM) who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti- CD38 monoclonal antibody. Although MM is generally treated by a combination of immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies, after patients progress on these options, few other therapies are available and outcomes tend to be poor.
An accelerated approval from the FDA allows for an abbreviated approval timeline using a surrogate end point to predict clinical benefit. Under the terms of the accelerated approval pathway for teclistamab-cqyv, which was granted on October 25, 2022, the FDA noted that continued approval may be contingent on verification and description of clinical benefit in confirmatory trial(s).
Other approved therapies include 2 chimeric antigen receptor (CAR) T-cell therapies, ciltacabtagene autoleucel (Carvykti; Janssen Biotech and Legend Biotech) and idecabtagene vicleucel (Abecma; Bristol Myers Squibb).1,2 CAR T-cell therapy, however, has limitations due to its risk of adverse events (AEs) and inaccessibility.
The approval of teclistamab-cqyv was based on results from the MajesTEC-1 trial (NCT03145181/NCT04557098), a phase 1/2, multicenter, open-label, single-arm study. The study included patients aged 18 years and older who had R/R MM and had previously received at least 3 prior lines of therapy.3 The median number of lines of prior therapy was 5 (range, 2-14), with 100% of patients having previously received at least 1 immunomodulatory drug, proteasome inhibitor, or anti-CD38 antibody. Overall, approximately 70% of patients had been exposed to at least 2 immunomodulatory drugs, at least 2 proteasome inhibitors, and at least 1 anti-CD38 antibody, and 81.8% had received a stem cell transplant.
Mechanism of Action
Teclistamab-cqyv is an off-the-shelf bispecific T cell–engaging antibody that binds to the CD3 receptor on T cells and B-cell maturation antigen expressed on MM cells and some healthy B-lineage cells. The drug then activates T cells and causes the release of proinflammatory cytokines, resulting in the lysis of MM cells.4
Dosage and Administration
The step-up dosing schedule for teclistamab-cqyv is:
Patients should be treated with teclistamab-cqyv until unacceptable toxicity or disease progression occurs. Premedications are recommended 1 to 3 hours prior to teclistamab-cqyv step-up doses; the first treatment dose should include a corticosteroid, an H1 antagonist, and antipyretics. Premedications may be necessary prior to subsequent doses in patients who repeat doses within the step-up dosing schedule or who experience cytokine release syndrome (CRS), an inflammatory reaction characterized by fever and potential organ failure. Patients are at highest risk of CRS within the first 3 step-up doses, requiring hospitalization for monitoring for 48 hours after the first treatment dose and each step-up dose.4
The most common AEs in patients receiving teclistamabcqyv are pyrexia (76%), injection site reaction (37%), fatigue (33%), musculoskeletal pain (44%), upper respiratory tract infection (26%), pneumonia (24%), nausea (25%), diarrhea (21%), and headache (25%). CRS occurred in 72% of patients, and tocilizumab (Actemra; Genentech) was administered to 36.4% of all patients who received teclistamab-cqyv. Neurotoxic events, including immune effector cell–associated neurotoxicity syndrome (ICANS), were reported in 14.5% of patients, with most reported as grade 1 or 2 events and 8.5% requiring supportive care with therapies including tocilizumab, dexamethasone (Decadron; Pfizer CentreOne), levetiracetam (Keppra; UCB), and gabapentin (Neurontin; ACI).2
During MajesTEC-1 (NCT04557098), the investigators noted that 1 patient had a dose reduction during cycle 21 because of recurrent neutropenia, 63% of patients skipped a dose because of AEs, and 2 patients discontinued teclistamab because of AEs (grade 3 adenoviral pneumonia and grade 4 progressive multifocal leukoencephalopathy). Additionally, 5 deaths occurred during the trial and were considered to be related to teclistamab. Specifically, 1 patient who died had discontinued teclistamab because of progressive multifocal leukoencephalopathy, 2 patients contracted COVID-19, 1 patient experienced hepatic failure, and 1 patient contracted streptococcal pneumonia.4
Warnings and Precautions
Teclistamab-cqyv has a black box warning for CRS, requiring a step-up dosing schedule and inpatient monitoring for 48 hours after each of the first 3 doses. It also has a black box warning for neurologic toxicity, including ICANS. Because of these risks, the drug is available only through the Risk Evaluation and Mitigation Strategy (REMS) program Tecvayli REMS. Prescribers, pharmacies, and health care settings will need to be registered and certified in the program to prescribe, dispense, and treat patients with the drug.4
Pregnancy and Lactation
No data are available for teclistamab-cqyv in pregnant women. However, because the agent is a humanized monoclonal antibody and IgG crosses the placenta, fetal exposure is expected, likely increasing as pregnancy progresses. Practitioners should verify pregnancy status prior to treatment initiation. Patients of childbearing potential should use contraception during therapy and for 5 months after the last dose.
Similarly, whether teclistamab-cqyv is present in breast milk is unknown. However, human IgG is present in breast milk, and it is expected teclistamab-cqyv would also be present in breast milk. Breastfeeding is not recommended during therapy and for 5 months after the last dose of teclistamab-cqyv.4
1. Yong K, Delforge M, Driessen C, et al. Multiple myeloma: patient outcomes in realworld practice. Br J Haematol. 2016;175(2):252-264. doi:10.1111/bjh.14213
2. Kumar SK, Callander NS, Adekola K, et al. Multiple myeloma, version 3.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2020;18(12):1685-1717. doi:10.6004/jnccn.2020.0057
3. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387(6):495-505. doi:10.1056/NEJMoa2203478
4. Teclistamab-cqyv. Package insert. Janssen Biotech Inc; 2022. Accessed January 16, 2023. www.accessdata.fda.gov/drugsatfda_docs/label/2022/761291s000lbl.pdf
About the Author
Emily Viehl, PharmD, BCOP, is a clinical oncology pharmacist at Smilow Cancer Hospital and Yale New Haven Health System in Connecticut.