FDA grants accelerated approval to talquetamab-tgvs for relapsed or refractory multiple myeloma
What is the potential role for Talquetamab-tgvs in the treatment of Multiple Myeloma?
- Talquetamab-tgvs is a first-in-class bispecific GPRC5D-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD)and an anti-CD38 monoclonal antibody. 1
- GPRC5D is a receptor commonly found on Multiple Myeloma cells. Its expression in normal tissue cells is limited, which makes it a promising therapeutic target.
- Talquetamab-tgvs activated T-cells cause the release of pro-inflammatory cytokines and result in the lysis of multiple myeloma cells.1
- Approval of this indication was based on the MonumenTAL-1 trial, a single arm, open-label, multicenter phase 2 study, in adults with relapsed or refractory multiple myeloma who had previously received at least four prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.2
- Patients (n=288) had received either talquetamab-tgvs 0.4 mg/kg subcutaneously weekly (n=143), following two step-up doses in the first week of therapy, or talquetamab-tgvs 0.8 mg/kg subcutaneously biweekly (n=145), following three step-up doses, until disease progression or unacceptable toxicity.
- The main efficacy measure was overall response rate (ORR). In the group receiving 0.4mg/kg weekly ORR was 74% with a median follow up of 14.9 months and in the group receiving 0.8 mg/kg biweekly ORR was 73% and median follow up of 8.6 months.
- Adverse events leading to dose reductions occurred in 8-15% and those leading to discontinuation occurred in 5-8% of patients.
- Cytokine release syndrome (CRS) was common (75-79%) but mostly low grade and immune effector cell-associated neurotoxicity (ICANS) occurred in 11% of patient who had not received prior T-cell redirecting therapy. 2
- The National Comprehensive Cancer Network (NCCN) lists talquetamab-tgvs as a preferred regimen (in addition to other bispecific and CAR-T therapies) for patients with previously treated multiple myeloma after at least four prior therapies including an anti-CD38 monoclonal antibody, a PI and and IMiD.3
- Although no head to head data is available when comparing ORR of other bispecific T-cell engagers in multiple myeloma, such as elranatamab-bcmm (ORR= 57.7%) and teclistamab-cqyv (ORR was 61.8%), talquetamab-tgvs had slightly better response rates. All three therapy options carry black box warnings for CRS and neurological toxicity. Talquetamab-tgsv is a first in its class due to its novel receptor target, GPRC5D, and it has also been shown to be effective in patients who have previously received T-cell directed therapies.2, 4-5
What role can the pharmacist play in the management of patients on [Talquetamab-tgvs]?
- Talquetamab-tgvs has complex administration requirements including a ramp up dosing schedule, different weekly and every 2 week dosing schemes and pre-medications requirements, which pharmacists can help to implement safely.
- Pharmacists can assist in educating patients and caregivers on signs and symptoms of CRS, neurological toxicities, oral toxicities, and risk of infection.
- Pharmacists can work with providers to select appropriate patients for talquetamab-tgvs and ensure compliance with Risk Evaluation and Mitigation Strategy requirements.
Clinical Pearls
- Due to the risks of cytokine release syndrome and neurological toxicity, including immune effector cell-associated neurotoxicity, Talquetamab-tgvs is only available through a restricted program called the Tecvayli and Talvey Risk Evaluation and Mitigation Strategy (REMS).1
- Unique common side effects of talquetamab-tgvs are nail changes (50%), dysgeusia (70%), and skin disorders (41%) .1
- Patients experiencing oral toxicity and weight loss should be provided with supportive care for grade 1-2
- For grade 3 oral toxicity and weight loss, withhold treatment until grade 1 or better
- Patients who experience grade 4 oral toxicity and weight loss should permanently discontinue talquetamab-tgvs.1
- Janssen offers financial assistant programs for patients with private or commercial insurance, and for uninsured patients.
- CarePath Savings Program for Talvey: Assist with lowering out-of-pocket cost for those with private or commercial insurance. Available at MyJanssenCarePath.com
- Johnson & Johnson Patient Assistance Foundation, Inc. (JJPAF): An independent, nonprofit organizations that gives eligible uninsured patients free prescription medicines donated by Johnson & Johnson companies.6
References
1.TALVEY (talquetamab-tgvs) [Prescribing Information] Horsham, PA: Janssen Biotech; Aug 2023
2.Schinke CD, Touzeau C, Minnema MC, et al. Pivotal phase 2 MonumenTAL-1 results of talquetamab (tal), a GPRC5DxCD3 bispecific antibody (BsAb), for relapsed/refractory multiple myeloma (RRMM). Journal of Clinical Oncology. 2023;41(16_suppl):8036-8036.
3.NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.1.2024. National Comprehensive Cancer Network, Inc. 2024. Accessed [October 9,2023].
4.TECVAYLI (teclistamab-cqyv) [Prescribing Information] Horsham, PA: Janssen Biotech; Aug 2023
5.ELREXFIO (elranatamab-bcmm) [Prescribing Information] New York, NY: Pfizer inc. Aug 2023
6.Jansen Care Path. https://www.janssencarepath.com/patient/talvey/cost-support Accessed November 14, 2023
