Dr Garfall on Updated Safety Data for Teclistamab in R/R Myeloma

Alfred L. Garfall, MD, MS, director, Autologous Hematopoietic Stem Cell Transplantation, section chief, Myeloma, Hematology-Oncology, Penn Medicine, associate professor of medicine (hematology-oncology), the Hospital of the University of Pennsylvania, discusses updated safety data reported from the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098) assessing teclistamab-cqyv (Tecvayli) in patients with relapsed/refractory multiple myeloma.

the FDA granted accelerated approval to teclistamab

 for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The regulatory decision was based on prior data from MajesTEC-1.

In updated safety findings from the study presented at the 

, no new safety signals were reported, which Garfall notes as an important finding for a new class of medication given continuously over the course of months. When evaluating a novel agent such as teclistamab, looking for unusual toxicities that emerge with increased follow-up is important, he says.

Garfall notes that infections remained the primary notable adverse effect (AE) reported during the study. Any-grade infections occurred in 78.8% of patients, and 55.2% of patients had grade 3 or 4 infections. Twenty-two patients experienced grade 5 infections during the study; however, 18 of those patients had grade 5 COVID-19, and with additional follow-up, no new grade 5 COVID-19 events were reported.

Over time, the rate of grade 3 infections generally declined, and Garfall explains that patients transitioning to dosing once every 2 weeks could have helped alleviate the risk of infection.

Additional safety data showed that with further follow-up, no changes in the rates of cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome were reported. Treatment-emergent AEs (TEAEs) led to dose reduction in 1 patient (0.6%), and 8 patients (0.4%) discontinued treatment due to TEAEs, including 5 patients who discontinued treatment due to infections.

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Alfred L. Garfall, MD, MS, discusses updated safety data for teclistamab in relapsed/refractory multiple myeloma.

 Dr Garfall on Long-Term Data for Teclistamab in Relapsed/Refractory Myeloma 

Alfred L. Garfall, MD, MS, director, Autologous Hematopoietic Stem Cell Transplantation, section chief, Myeloma, Hematology-Oncology, Penn Medicine, associate professor of medicine (hematology-oncology), the Hospital of the University of Pennsylvania, discusses updated findings from the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098) assessing teclistamab-cqyv (Tecvayli) in patients with relapsed/refractory multiple myeloma.

 showed that at a median follow-up of 30.4 months, 38 patients remained on the treatment, including 37 who switched to a less frequent dosing schedule of once every 2 weeks vs once every week. Notably, in February 2024, findings from MajesTEC-1 also 

supported the FDA approval of teclistamab at a reduced dose

 of 1.5 mg/kg every 2 weeks in patients with relapsed/refractory multiple myeloma who have achieved and maintained a complete response (CR) or greater for at least 6 months.

Long-term data showed that the overall response rate (ORR) was 63.0% among all patients treated at the recommended phase 2 dose (n = 165), including a CR or better rate of 46.1%. Additionally, 87.7% of evaluable patients (n = 48 of 56) achieved minimal residual disease (MRD) negativity at a 10-5 sensitivity at any point. for a minimum of 6 months. MRD negativity was sustained for a minimum of 6 months in 56.1% of evaluable patients (n = 23 of 41) and a minimum of 12 months in 38.9% of patients (n = 14 of 36).

In all patients, the median progression-free survival (PFS) was 11.4 months (95% CI, 8.8-16.4). In those who experienced a CR or better (n = 76), the median PFS was not reached (95% CI, 26.9–not evaluable [NE]). Patients who had a very good partial response or better (n = 98) achieved a median PFS of 26.7 months (95% CI, 19.4-NE).

Alfred L. Garfall, MD, MS discusses updated long-term data for teclistamab in patients with relapsed/refractory multiple myeloma.

Dr Garfall on Long-Term Data for Teclistamab in Relapsed/Refractory Myeloma 

Alfred L. Garfall, MD, MS, assistant professor of medicine, the Hospital of the University of Pennsylvania, discusses the potential of CAR T-cell therapy in multiple myeloma.

CAR T-cell therapy has shown high response rates in heavily pretreated and high-risk patients multiple myeloma, says Garfall.

The modality has been shown to lead to extended treatment-free remissions. Although the majority of patients with multiple myeloma who receive CAR T-cell therapy will relapse, the modality has shown potential for long-term immune surveillance against relapse, concludes Garfall.

Alfred L. Garfall, MD, MS, discusses the potential of CAR T-cell therapy in multiple myeloma. 
 

Dr. Garfall Discusses CAR T-Cell Therapy in Multiple Myeloma

Alfred L. Garfall, MD, MS, assistant professor of Medicine, the Hospital of the University of Pennsylvania, discusses the impact of chimeric antigen receptor (CAR) T-cell therapy in hematologic malignancies.

The use of CAR T-cell therapies for patients with hematologic malignancies has become a very remarkable and translational medicine story that has played out over the last 20 years, Garfall explains. This type of treatment has also come into clinical application use in the last 5 years with pilot and multicenter studies that are targeting CD19 with CAR T cells in patients with various B-cell malignancies, he adds. Another target includes BCMA in multiple myeloma. Soon, the community could see the first FDA approval of CAR T-cell therapy.

An ongoing conversation among oncologists is discussing the various data available for CAR T-cell therapies explored in chronic lymphocytic leukemia, acute lymphoblastic leukemia, and non-Hodgkin lymphoma and comparing the response rates and safety profiles, he adds.

Dr. Garfall on Impact of CAR T-Cell Therapy in Hematologic Malignancies

Alfred L. Garfall, MD, MS, assistant professor of Medicine, the Hospital of the University of Pennsylvania, discusses chimeric antigen receptor (CAR) T-cell therapy in acute lymphoblastic leukemia (ALL).

Studies have now progressed to the point where there are enough patients treated to ascertain certain patterns of response and resistance across different malignancies, Garfall explains.

In ALL, there are 90% response rates with CAR T-cell therapy in patients who are refractory to all other therapies. However, a sizeable portion of those patients will relapse and, in most cases, those relapses will be selection for CD19-negative disease, where the leukemia has managed to eliminate the target of the CAR T cell.

Alfred L. Garfall, MD, MS, assistant professor of Medicine at the Hospital of the University of Pennsylvania, discusses CAR T-cells in acute lymphoblastic leukemia (ALL).

Alfred L. Garfall, MD, MS

Articles

Dr Garfall on Updated Safety Data for Teclistamab in R/R Myeloma

Dr Garfall on Long-Term Data for Teclistamab in Relapsed/Refractory Myeloma

Dr. Garfall Discusses CAR T-Cell Therapy in Multiple Myeloma

Dr. Garfall on Impact of CAR T-Cell Therapy in Hematologic Malignancies

Dr. Garfall on CAR T Cells in ALL