Urvi A. Shah, MD, Assistant Attending at Memorial Sloan Kettering Cancer Center and Assistant Professor at Weill Cornell Medicine, New York, moderated the session where the MagnetisMM trial updates1,2 were reported and was interviewed by The ASCO Post.
Urvi A. Shah, MD
Elranatamab vs Teclistamab
Dr. Shah noted that elranatamab could join an ever-expanding landscape of bispecific antibodies in multiple myeloma, the first of which to be approved is teclistamab. Both elranatamab and teclistamab3 target B-cell maturation antigen (BCMA) and the CD3 receptor, and according to Dr. Shah “appear to be comparable in many ways.” Based on clinical trial data, however, the incidence of cytokine-release syndrome and immune effector cell–associated neurotoxicity syndrome (ICANS) appears slightly lower with elranatamab, although with both drugs the vast majority of these cases have been of low grade. Therefore, she said, any differences in this regard are probably not clinically significant.
“At this point, there’s no clear separation showing that elranatamab is significantly different from teclistamab, and teclistamab has the advantage of being the first to market and of having a comfort level with physicians,” Dr. Shah said. “The progression-free survival data for elranatamab from MagnetisMM-1 looks very similar, although it’s not yet available for MagnetisMM-3, and if that is very different, then it could be a factor.”
Update on Talquetamab
Elranatamab and teclistamab both target BCMA and the CD3 receptor, whereas the other bispecific making headlines—talquetamab—targets CD3 and the G protein–coupled receptor family C group 5 member D (GPRC5D). Updated findings for talquetamab from the phase I/II MonumenTAL-1 trial were also presented at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition, showing responses in 70% of heavily pretreated patients, including many with prior T-cell–redirecting therapy.4
“Since they have different targets, we can sequence these drugs. Many patients will need talquetamab after experiencing disease progression on BCMA-targeted treatment. If talquetamab poses less severe neutropenia and infectious risk in the real world [promising published data], it may be preferred before teclistimab once it is approved, though this drug also has common but mild side effects of dysgeusia, skin and nail changes which may be challenging for some,” Dr. Shah commented.
Thus, clinicians will likely have several bispecific monoclonal antibodies from which to choose in relapsed or refractory myeloma. This choice will probably revolve around a number of factors, including ease of access, duration of therapy (fixed duration will be preferred over continuous), ease of administration (subcutaneous administration will be preferred over intravenous), dosing schedule (every 3 weeks will be preferred over weekly), risk of infection (a concern with this class of agents), risk of cytokine-release syndrome and ICANS, progression-free survival, and cost, she said.
Risk of Infection and Soluble BCMA
It is important with this class of drugs to address the risk of infection and to consider appropriate prophylaxis, Dr. Shah continued. “The precautions we take for our transplant patients will need to be considered with bispecifics in myeloma.”
Essentially all patients on bispecific antibodies should receive acyclovir and, under certain conditions, other agents. Patients with immunoglobulin levels less than 400 mg/dL may warrant intravenous immunoglobulin; those with prolonged neutropenia may need prophylactic antibiotics; and those with a history of fungal infections may require antifungals. Some clinicians consider prophylaxis for Pneumocystis carinii pneumonia across the board, whereas others use a CD4 threshold (often < 200 cells/μL), as is done in treating human immunodeficiency virus. It is important to maintain vigilance for risk of viral reactivation as well, such as cytomegalovirus and adenovirus, and consider prophylaxis in appropriate situations, Dr. Shah added. Clinical trials on the appropriate prophylaxis and real-world data on infection risk are needed.
Finally, Dr. Shah said research data on soluble BCMA levels in patients receiving these drugs is interesting and correlates with disease burden and response, though at this time, this has not yet been approved for use in the clinic. In MagnetisMM-1, responders to elranatamab had reductions in soluble BCMA over time, suggesting it could be a prognostic and perhaps predictive marker. There is no currently validated test for soluble BCMA, but if its usefulness as a biomarker becomes clear, it could further refine myeloma risk models and help guide treatment, she said.
DISCLOSURE: Dr. Shah has served as a consultant to Sanofi, Bristol Myers Squibb, and Janssen.
REFERENCES
1. Bahlis NJ, Tomasson MH, Mohty M, et al: Efficacy and safety of elranatamab in patients with relapsed/refractory multiple myeloma naive to B-cell maturation antigen (BCMA)-directed therapies: Results from Cohort A of the MagnetisMM-3 study. 2022 ASH Annual Meeting and Exposition. Abstract 159. Presented December 10, 2022.
2. Raje N, Bahlis NJ, Costello C, et al: Elranatamab, a BCMA targeted T-cell engaging bispecific antibody, induces durable clinical and molecular responses for patients with relapsed or refractory multiple myeloma. 2022 ASH Annual Meeting and Exposition. Abstract 158. Presented December 10, 2022.
3. Moreau P, Garfall AL, van de Donk NWCJ, et al: Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med 387:495-505, 2022.
4. Chari A, Touzeau C, Schinke C, et al: Talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma: Phase 1/2 results from MonumenTAL-1. 2022 ASH Annual Meeting and Exposition. Abstract 157. Presented December 10, 2022.
