Teclistamab Toxicities Highly Manageable in R/R Multiple Myeloma

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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.

CASE SUMMARY

  1. A 63-year-old man was diagnosed 8 years ago with multiple myeloma (IgG-kappa)​
  2. He lives in a rural community.​
  3. He now presents with penta-refractory disease progression.
  4. Completed 4 prior lines of therapy, which included autologous stem cell transplant, 2 proteasome inhibitors, 2 immunomodulatory drugs, and 1 anti-CD38 antibody​.

Medical History

  • Hypertension controlled with lisinopril​.
  • ECOG performance status: 1

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

Ajay Nooka, MD, MPH

Director, Myeloma Program

Department of Hematology and Medical Oncology

Scientific Director

Winship Data and Technology Applications Shared Resource

Winship Cancer Institute​

Emory University School of Medicine​

Ajay Nooka, MD, MPH

Director, Myeloma Program

Department of Hematology and Medical Oncology

Scientific Director

Winship Data and Technology Applications Shared Resource

Winship Cancer Institute​

Emory University School of Medicine​

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.

References:

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

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