Trial-In-Progress Looks to Prophylactic Tocilizumab to Reduce CRS in Patients with Multiple Myeloma

Robert Rifkin, MD, FACP, a medical oncologist and hematologist with Sarah Cannon Research Institute at Rocky Mountain Cancer Centers (part of the US Oncology Network), Denver, CO, spoke to Pharmacy Times about prophylactic tocilizumab (Actemra; Genentech) to mitigate cytokine release syndrome (CRS) associated with teclistamab (Tecvayli; Janssen Biotech, Inc.) for patients with multiple myeloma (MM) at the 65^th American Society of Hematology (ASH) Annual Meeting & Exposition, which took place December 9-12, 2023, in San Diego, California.

PT Staff: Can you discuss the phase 2 Optec study, which will evaluate prophylactictocilizumab for patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM) in the outpatient setting?

Robert Rifkin, MD, FACP: So it's my pleasure to present it ASH this year. And this is a little unusual for me because I'm going to present a trial-in-progress abstract, instead of results of a clinical trial.

But I think that's extraordinarily important in the MM subpopulation that you just identified, we're going to be studying teclistamab, which was the first approved bispecific antibody in the treatment of MM with a B-cell maturation antigen (BCMA) target. This is different because, when the drug was approved with the FDA label, there was a mandate for hospitalization. And the goal of this trial is actually, by changing the strategy to bring teclistamab into the outpatient setting, to hopefully show with convincing safety data that you don't need to be hospitalized for all of the step-up doses.

So this is a little bit unique— we will be following the FDA-approved label, which as you pointed out is myeloma patients who are heavily exposed, and this would be after your fourth line of therapy. But our strategy is going to be different. We're going to strike, if you will, preemptively to prevent the known complications of CRS. And Immune effector cell-associated neurotoxicity syndrome (ICANS), the neurologic complications.

Toward that end, we're going to be giving people prophylactic tocilizumab, a drug that's used commonly to treat CRS, and some corticosteroids. And we hope, based on preliminary data from others, that we can significantly decrease the risk of CRS and ICANS, and hopefully that'll allow this to be available to a lot more patients and make access and administration considerably more simple.

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PT Staff: What is the importance of focusing on CRS as an adverse event?

Robert Rifkin, MD, FACP: It really didn't come to the forefront until we started doing CAR T-cell therapies, as everybody knows, and CRS and ICANS were very well known there. And there's all kinds of grading systems and management programs.

And we knew that, with the advent of bispecific antibodies and now even some trispecific ones in early clinical trials, that these are well-known complications.

We know, for example, the incidence. We know a lot about the severity, [and] we know a lot about the time to onset. So all of these— with all of the rapid advances in myeloma therapy—are sort of a new class of toxicities. And so we need to learn how to very effectively manage these and hopefully ameliorate them so that they're all grade 1 and easily managed in the outpatient setting.

So the study is a little bit unique, in that we're going to follow the label exactly, and at the request of regulatory agencies we're going to do pharmacokinetics (PK) and pharmacodynamics (PD) to demonstrate [that] hopefully there are no issues using this strategy or that we're going to diminish the efficacy of our treatment. So we'd be very looking very closely at the first 5 and first 10 patients.

PT Staff: How can low quality of life impact patient outcomes?

Robert Rifkin, MD, FACP: So this is a difficult myeloma population because they've already failed multiple lines of therapy. They may have even failed CAR - cells, for example. And it's a whole new class of drugs, which— in myeloma every few years we have an explosion of novel agents and new classes of therapies— [come with] new toxicities. And they're important because, in this frailer population, they can get quite ill very quickly, so that's why really the focus of this trial and progress is a safety endpoint. That's a little bit different than a traditional clinical trial when you're developing drugs.

PT Staff: How might findings from the Optec study impact the treatment and management of patients with this disease?

Robert Rifkin, MD, FACP: I think the first thing (as you move into the outpatient setting) you have to have is all of the right things on hand. And that's not just only the drug, but it's the agents used to treat CRS and the ability to monitor patients closely. And so you'll in all of the bispecific trials [that] it's a requirement that you have a caregiver 24/7. And we're educating the caregivers how to recognize complications early, whether it's something like just an increase in heart rate, or maybe a low-grade fever, and that's much different than traditional chemotherapy—it trips a switch to, I guess, to raise the alarm if you will.

And importantly, in all of these trials, all of the patients carry a wallet card. And on there is the attending physician and their cell phone number so that there are no layers and then they go to centers intentionally very close to our trial—[that way we] are well equipped to handle and manage this. They usually have considerable CAR T-cell experience and some bispecific antibody experience.

I think the biggest challenge for us is the availability of hospital beds if you need them, and then the rapid turnover in our industry, just like everybody else, and [new staff] have to be retrained when you get new ones.