ASH 2024 | Tocilizumab prophylaxis for patients with RRMM treated with teclistamab, elranatamab, or talquetamab

The introduction of bispecific monoclonal antibodies to the field of multiple myeloma has been found to translate into great, deep and durable responses for many patients. When it comes to the safety profile, most of the new side effects we have seen are around the first dose or the first few doses during the step-up dosing. Cytokine release syndrome with fever, drops in blood pressure, or more severe organ symptoms for higher grades of CRS is something that has been seen with CAR T-cell therapy. You can see, for the most part, grade 1 or grade 2 CRS reactions in patients who get these bispecific antibodies, and it’s mostly around the first dose. Looking at the registrational trials for teclistamab, the first BCMA/CD3 targeted bispecific antibody and also elranatamab, which is the second of the same class, and talquetamab, that’s the GPRC5D/CD3 bispecific antibody. You can see across the board that the rate of CRS is 60, 70, or even higher, 80% for the first dose or so. So part of the reason that we still apply hospitalization for the step-up dosing is really the fact that patients develop these type of symptoms. There are also the immune cell-associated neurological syndromes or the ICANS that can happen, but mostly the CRS is what keeps the patient in the hospital. So looking at how you treat CRS, standard approach would be to consider giving tocilizumab, the IL-6 receptor inhibitor, and you can also use steroids, and you can repeat these types of measures. You can also give fluids and other types of strategies if the symptoms are more severe. So the first study that looked into the utility of using an IL-6 receptor inhibitor was the trial that was published two years at ASH, or presented at ASH. It’s not yet published. Suzanne Trudel from Toronto presented data using the FcRH5/CD3 bispecific antibody. The data was very promising. They showed it could reduce the rate of CRS. That triggered us to think about, could we potentially utilize this in the standard of care setting? Our institution made the decision to include prophylaxis with tocilizumab, the IL-6 receptor inhibitor, as a single dose, one hour before the first dose of any of the commercially available bispecific antibodies. And Andrew Kowalski, our clinical pharmacist, presented at this ASH how the rate of CRS from published 75-80% can be dropped down to less than 10%. And we are virtually only seeing grade one CRS in those patients. I think it’s really an improvement for patient experience. You can shorten the hospitalization if you do inpatient. Instead of giving the first dose and having two waiting days, you observe and manage CRS and then you give the next dose. And if you give teclistamab, you have two more waiting days and then you give the next dose. You can really shrink it down to have dose, wait, dose, wait, dose. And it also sets the stage for thinking about how this could become outpatient. So a lot of excitement about this. And the questions that Andrew got after his presentation is, why is this not standard of care? And can I please have a copy of your slide? So I think there’s a lot of excitement. And hopefully, the data will be written up and published soon.

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