In the second article of a 2-part series, Ajay Nooka, MD, MPH, discussed the exciting safety profile of teclistamab and how to manage major adverse events, like cytokine release syndrome, for patients with relapsed/refractory multiple myeloma.
Targeted OncologyTM: What do you consider when handling toxicities from teclistamab-cqyv (Tecvayli) seen in the MajesTEC-1 study (NCT04557098)?
AJAY NOOKA, MD, MPH: There are 3 major special adverse events [AEs] that I usually stress on when I when I speak about bispecific antibodies. [The first to consider are the] cytopenia and infection risks, then the second major AE is the cytokine-release syndrome [CRS] rates, and the third one is neurotoxicity.1
What was the prevalence of CRS with this treatment and how do you recommend handling it?
CRS was seen in 72.1% of the patients,2 but the CRS from CAR T-cell therapy is very different than the CRS from bispecific antibodies.… They were mostly grade 1 CRS events, and grade 2 CRS happened 20% of the time, but what we also learned during this time is that CRS further propagation can be mitigated by acting early. You can potentially [cut this off] by giving tocilizumab [Actemra]. In the Transplant and Cellular Therapy guidelines, tocilizumab is for grade 2 CRS, and in the trial for patients with grade 2 CRS...the usage of tocilizumab is in the range of almost 40% of patients who received it.3
The reason [for this] is that our threshold to give it has started to get lower and lower, so that [physicians can] act early when the patient has grade 1 CRS. This prevents further propagation, especially when there is no impact on the response [to treatment], as tocilizumab did not have any impact on the [patient's response to treatment], and it was able to dampen the CRS and mitigate them to a grade 1 AE. So CRS is easily manageable, the usage of tocilizumab earlier is better, and the take home message [is that this usage of it to manage] CRS did not impact any of the responses to treatment.2 If this is the biggest concern for anybody [when sending a patient] to an academic center, now we have some data that [shows for] patients who receive prophylactic tocilizumab, you can minimize [this AE] even before the patients have grade 1 CRS, fully understanding that 30% of the patients who did not have any CRS will still be receiving [tocilizumab].
How can you minimize infections with this treatment?
These T cells...are redirected for a very different purpose. They are redirected to kill the myeloma cells, which basically leaves a huge hole in the different systems, and suddenly, you're seeing that infection risk to be significantly higher. The infection risk was [approximately] 76%, and grade 3 or 4 infections were [seen in 44.8% of patients].2 The patients [who are experiencing infections] are heavily refractory patients with multiple myeloma who do not have the best immune system.
By giving the bispecific antibodies, you're potentially increasing [their chance] for a higher infection risk potential. What we can do to minimize this is identify those specific patients [in order to] increase their layers of protection. Anybody who we have started on the B-cell maturation antigen [BCMA]-targeted bispecific antibody gets [intravenous immunoglobulins] on a monthly basis and anybody who has lymphopenia is already on a prophylaxis...[but everybody will] get a wider prophylaxis. During the first month or so, we also use levetiracetam [Keppra] to prevent any [immune effects from] neurotoxicity. So, increasing prophylaxis can help the patients to still get the benefit of these drugs, and at the same time, not have a lot of toxicities.
What about the toxicity profile of teclistamab stands out to you?
Altogether, whenever I talk about any...AE for a drug I look at the discontinuation rates. [In the MajesTEC-1 trial, you] have 165 patients, and the patients who discontinued the drug because...[of an AE was] extremely low [at 1.2%].2 I have never seen this for any other agent, including daratumumab [Darzalex]. So these drugs are well tolerated, and you need to know what to look for, which are the 3 things I was talking about the CRS, infections, and neurotoxicity. Once you're able to manage those, [teclistamab] could be given easily.
1. van de Donk NWCJ, Moreau P, Garfall A, et al. Long-term follow-up from MajesTEC-1 of teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41(6):8011. doi:10.1200/JCO.2023.41.16_suppl.8011
2. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022 Aug 11;387(6):495-505. doi:10.1056/NEJMoa2203478
3. Banerjee R, Marsal J, Huang CY, et al. Early time-to-tocilizumab after B Cell Maturation Antigen-directed chimeric antigen receptor T cell therapy in myeloma. Transplant Cell Ther. 2021;27(6):477.e1-477.e7. doi:10.1016/j.jtct.2021.03.004