Supportive Care Helps Manage AEs With Teclistamab in R/R Multiple Myeloma

Hana F. Safah, MD

Professor of Clinical Medicine

Section of Hematology and Medical Oncology

Director, Stem Cell Transplantation Program and the Leukemia and Lymphoma Programs

Tulane University School of Medicine

New Orleans, LA

Targeted Oncology: What data support the use of teclistamab (Tecvayli) in patients with relapsed/refractory (R/R) multiple myeloma?

Hana F. Safah, MD: The MajesTEC-1 trial [NCT03145181, NCT04557098] was the first-in-human phase 1/2 open-label, multicohort, multicenter, dose escalation study that looked at teclistamab in patients with R/R multiple myeloma who previously received more than 3 lines and were triple class exposed. These patients were B-cell maturation antigen [BCMA] naive. The treatment was using the step-up dose of teclistamab at 0.06 and 0.3 mg…then the treatment dose was 1.5 mg/kg on a weekly basis. They continued with the treatment until progression, and they followed all patients 2 years after.

The primary end point was looking at overall response rate [ORR]. The key secondary end point was looking at the duration of response and the depth of response as well as minimal residual disease [MRD] status. It’s very important to evaluate MRD status when patients with multiple myeloma, especially after induction, after stem cell transplant, and as we are doing these BCMA-targeted therapies, because we're learning MRD negativity correlates very well with prolonged progression-free survival [PFS] and overall survival [OS].

How do you evaluate MRD in patients with multiple myeloma?

That's still the problem with multiple myeloma. It's different from acute lymphoblastic leukemia, where it's flow cytometry. Here, when you look at clinical trials, every clinical trial looked at MRD negativity in a different assay, some next-generation sequencing [NGS], some polymerase chain reaction, and some flow cytometry. The one I prefer is the Mayo Clinic NGS, and it's available, and that's what we use right now in the practice.

How did patients perform in the trial in terms of efficacy?

These were the patient characteristics: those older than age 75 were a good number, almost [15%].¹ When we look at patients who are difficult to treat, it's usually patients with extramedullary disease. These are patients who don't do well with their multiple myeloma. They have a higher risk of early mortality, [as do those with] high-risk cytogenetics. A good number of those patients were enrolled in the trial [17.0% with extramedullary disease and 25.7% with high-risk cytogenetics]. Triple refractory and penta-drug refractory had a good representation [77.6% and 30.3%, respectively].

In these patients who are triple class refractory, the outcome was really good. When you look at the primary end point of overall response, it was 63% in this patient population [including some with] extramedullary disease, with one-third of them having high risk.² The depth of response of complete remission [CR] or better was seen in 46%. Looking at the duration of response, the median duration for the overall population was 24 months [95% CI, 17.0-not estimable (NE)]. Looking at those who achieved CR or better, it was not reached [95% CI, 26.7-NE]. This is really good in that patient population. Looking at the 30 months duration of remission, it was 45% overall. With those who achieved CR or better it was 60%. Those are really good data. When we look at the PFS, the median was 11 months. The median for OS was 22 months [95% CI, 15.1-29.9].

What were the safety outcomes with teclistamab?

It’s impressive with respect to efficacy. So what's stopping us when we look at safety? It does cause cytopenias. These are BCMA-targeted antibodies, but because of the cytokines, because of severe inflammation, patients end up with anemia. They can also cause thrombocytopenia and neutropenia. You need to follow your patients and support them when you when you treat them with teclistamab. You can use growth factors. You have to support them with transfusion. You can even use erythropoiesis-stimulating agents to help them with anemia.

Cytokine release syndrome was seen in 72% at any grade. Grade 3 to 4 was [less than] 1%, but when we look at any-grade we're not talking about only grade 1; we're talking about grade 2. When we talk about grade 2, it's fever and hypotension, and these patients usually behave like patients with sepsis, and they might go to the intensive care unit. That was seen in that study.

How do you address infections in patients receiving teclistamab?

Infection is something common with these bispecifics because…patients with multiple myeloma are very immunosuppressed to start with, and they suffer from hypogammaglobulinemia. Then comes the treatment that leads to worsening of the hypogammaglobulinemia. Bispecifics are notorious for decreasing the immunoglobulins. They really bottom out. This is where you have to follow the immunoglobulin level, even before they start having infections, and give them intravenous immunoglobulin [IVIG]. They need support with IVIG to prevent it, and you can minimize the risk of infection with the bispecific antibodies. I would put them on prophylaxis for viral infection, acyclovir for herpes, and I would I would put them on prophylaxis for Pneumocystis jirovecii pneumonia.

However, discontinuation because of adverse events was only seen in 4.8% [n = 8, 5 due to infection] and dose reduction was used in 0.6% [n = 1].

_References:

_{1. 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}

_{2. Garfall AL, Nooka AK, van de Donk NWCJ, et al. Long-term follow-up from the phase 1/2 MajesTEC-1 trial of teclistamab in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2024;42(suppl 16):7540. doi:10.1200/JCO.2024.42.16_suppl.7540}