Prophylactic Tocilizumab Could Increase Community Access to Bispecifics for MM

Prophylactic tocilizumab has the potential to decrease cytokine release syndrome and neurotoxicity for bispecific antibodies, explained Robert Rifkin, MD, a medical oncologist and hematologist with Rocky Mountain Cancer Centers. Decreasing the risk of these adverse events could increase patient access to these therapies by making it easier to administer them in an outpatient community setting.

OPTec study1 evaluates the use of prophylactic tocilizumab in patients with relapsed/refractory multiple myeloma receiving the bispecific antibody teclistamab. Initial results suggest prophylactic tocilizumab may reduce the risk of developing cytokine release syndrome and enable safer outpatient administration. The study has ongoing enrollment for further evaluation.

This transcript has been lightly edited.

Transcript

Your study is adding a cohort to receive prophylactic tocilizumab ahead of talquetamab. Are there even greater potential benefits for preventing adverse events for patients taking this therapy?

There are. The way the OPTec study is designed, when we reach 25 patients, we'll open a talquetamab arm again with prophylactic tocilizumab to try to decrease cytokine release syndrome and neurotoxicity. Unlike teclistamab, where the major issue is infections, in talquetamab, it's a bit of a different toxicity story in that there can be dysgeusia, hair and nail changes, weight loss, and loss of appetite. So, as part of that, we're actually putting in strategies to ameliorate, or at least attenuate, that set of unique toxicities. And they'll still be followed for infection, obviously.

What is the potential for prophylactic tocilizumab for patients who may be given the dual bispecific regimen (RedirecTT) or the trispecific under development that combines the 3 targets in talequetamab and teclistamab with less toxicity?

We're looking at all of those. There is a trial out there called RedirecTT-1,2 where you receive both talquetamab and teclistamab, and it has amazing results. The trispecific antibodies are coming along nicely in development. You still have the same sort of basic issues with cytokine release syndrome and neurotoxicity, but all of the agents going forward, a lot of them are being engineered to turn down the CD3, which will turn down cytokine release syndrome and other things. In addition, some of the new studies will have debulking to get rid of a lot of myeloma before they go on therapies like this, which should decrease the toxicity as well. So, a lot of new strategies.

Regarding the use of prophylactic tocilizumab, clinicians have raised concerns over cost, particularly out-of-pocket costs for Medicare beneficiaries. Could your study lead to a new indication and Medicare coverage for tocilizumab?

This is a very interesting question. If you look at all of the labels for bispecific antibodies and CAR [chimeric antigen receptor] T, they're notoriously silent regarding tocilizumab. And that's very deliberate on the behalf of the regulators, because tocilizumab is not on any clinical pathways for this, nor does it have the indication. In an ideal world, the FDA would like us to redo a study that would be label enabling for that, but it's never going to happen. And it's hard. On studies, we try to get it supplied, obviously, because it's part of an investigation. With Medicare, it's always going to be an issue, but I think if you persist a lot of times, you can get it taken care of. So don't get frustrated.

Reference

1. Rifkin R, Schade H, Simmons G, et al. Optec: a phase 2 study to evaluate outpatient step-up administration of teclistamab in patients with relapsed/refractory multiple myeloma (RRMM): updated results. Presented at: ASH 2024; December 7-10, 2024; San Diego, CA. Abstract 4753.

2. Cohen Y, Morillo D, Gatt ME, et al. First results from the RedirecTT-1 study with teclistamab (tec) + talquetamab (tal) simultaneously targeting BCMA and GPRC5D in patients (pts) with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41(suppl 16). doi:10.1200/JCO.2023.41.16_suppl.80