Understanding Risks and Training Needs for Outpatient Bispecific Usage

Robert Mancini, PharmD, BCOP, FHOPA

BMT/Heme Pharmacy Program Coordinator

PGY2 Oncology Pharmacy Residency Director

St. Luke’s Cancer Institute

Boise, ID

[Read Part 1]

Targeted Oncology: Which bispecific T-cell engagers [BiTEs] are now available for use in hematologic malignancies?

MANCINI: There are 6 BiTEs currently on the market; we didn’t include blinatumomab [Blincyto], though technically that is a BiTE, but that is a continuous infusion…and has been around for quite some time.

The first 3 are elranatamab-bcmm [Elrexfio], teclistamab-cqyv [Tecvayli], and talquetamab-tgvs [Talvey], [which are] multiple myeloma drugs.^1-3 Epcoritamab-bysp [Epkinly] and glofitamab-gxbm [Columvi] are for patients with diffuse large B-cell lymphoma and more aggressive lymphomas, then mosunetuzumab-axgb [Lunsumio] is a follicular lymphoma drug.^4-6 Those last 3 all have the same target; they’re all anti-CD20, but they do have differences.

Epcoritamab and glofitamab have the same indication but mosunetuzumab is for that indolent lymphoma.^4-6 Then of the first 3, elranatamab and teclistamab are essentially the same drug, a B-cell maturation antigen–targeting bispecific, [whereas] talquetamab targets GPRC5D, so it is different.

What risks and mitigation strategies are present for each of the BiTEs?

All of them have risk of CRS [cytokine release syndrome] and ICANS [immune effector cell–associated neurotoxicity syndrome], but only the myeloma drugs have the REMS [Risk Evaluation and Mitigation Strategy] requirement.^1-6

If you look at the package inserts, pretty much all of them with the exception of mosunetuzumab have some type of recommendation for hospital admission or observation.^1-5 For elranatamab, it is for the first 2 doses; for teclistamab, it’s for the first 3; for talquetamab, it is the first 3 or 4 depending on which dosing regimen you look at.^1-3 For epcoritamab, it’s for day 15 of cycle 1, which is the first full treatment dose.⁴ Then for glofitamab, it is cycle 1, day 8, which is the first dose because with glofitamab, cycle 1, day 1 is [only] a dose of obinutuzumab [Gazyva], which they get for B cell depletion.5 For glofitamab, it’s for the first dose of the drug that inpatient observation is recommended.

There are a lot of ways to approach that, and investigators have looked at trying to move these patients into the outpatient setting. But that does make things a little bit more resource-intensive. However, in our experience, we’re going to be doing our first fully outpatient use of teclistamab next week. We’ll see how that goes. But so far [I believe we’ve treated] 5 patients with epcoritamab, and of the ones that have made it up to cycle 1, day 15, we haven’t had to admit any of them yet. Even with that recommendation, we’re able to manage these patients in an outpatient setting with appropriate monitoring.

All of these products have financial assistance available through the manufacturers and preferences. In terms of [requiring availability of] tocilizumab [Actemra], if you look at some of the CRS guidelines, that is a recommendation for management of CRS. Unlike chimeric antigen receptor T-cell therapy, which requires you to have 2 doses of tocilizumab on hand at all times, none of these products require that,^1-6 so it’s up to your clinic on whether or not you would consider giving tocilizumab in the outpatient setting. Now, for inpatients it is obviously a little bit different. But the thing to consider is that if you are going to use this and build tocilizumab into your treatment protocols, I would make sure that you’re authorizing the tocilizumab upfront [with insurance], because you don’t want to get into a situation where the patient needs it and you want to give it but then you don’t have that authorization for it. If you’re going to build into your protocols, the use of tocilizumab in the outpatient setting, [get that authorized] at the same time that your [treatment] is authorized.

Have you used tocilizumab in the outpatient setting?

We prefer dexamethasone as our primary treatment for CRS…so we don’t routinely use tocilizumab. But I know there are a lot of centers that prefer tocilizumab over dexamethasone, for reasons similar to their using CAR [chimeric antigen receptor] T-cell therapy. Only if you plan to give tocilizumab on the clinic side or the outpatient side, would you require that prior authorization.

We have not on the outpatient side. If a patient on any of these products required tocilizumab, they’re usually in the hospital by that point. But I know there are centers that I’ve talked to that use tocilizumab in the outpatient setting for grade 1 CRS. Just make sure you’re thinking about the cost and that prior authorization. Luckily, there should be a biosimilar tocilizumab coming out, which will hopefully reduce some of the costs.

Who should be involved in management of adverse events related to BiTEs administered in the community practice setting?

For protocol development, making sure you have that outline. Next is making sure you’re educating your staff on everything that’s important. How do we identify these patients? [When] they come into clinic, is it all on the physicians to be able to identify this or are we relying on our support staff to help us identify these patients? And if so, what do they do about it? It’s not only our staff…we have to think about the emergency department as well. So if we have an association, we’re telling our patients to go to a specific emergency department, your emergency department if your practice has one, making sure that they are aware of what these drugs are, and what to do if a patient comes through that. That education process is important.

Third is educating not only your patients, but their caregivers. I think caregivers are essential to successful treatment of these patients, especially up front in the outpatient setting, and making sure that we’re educating our patients on what symptoms to report, and when and who to call. A lot of times, patients will be told to call an after-hours line and they may get hold of an on-call oncologist who may not know the patient or hasn’t used this particular drug. For us, we instruct our patients when they call to make sure on the after-hours line, they specifically ask for the on-call bone marrow transplant/hematology physician who manages that patient. And [tell the patient] when to go to the emergency department.

_References:

_{1. Elrexfio. Prescribing information. Pfizer, Inc, 2023. Accessed November 30, 2023. https://tinyurl.com/45se87z6}

_{2. Tecvayli. Prescribing information. Janssen Pharmeceutical Companies, 2022. Accessed November 30, 2023. https://tinyurl.com/46axb2c4}

_{3. Talvey. Prescribing information. Janssen Pharmaceutical Companies; 2023. Accessed November 30, 2023. https://tinyurl.com/4tczj285}

_{4. Epkinly. Prescribing information. Genmab A/S, 2023. Accessed November 30, 2023. https://tinyurl.com/4n6bv3cd}

_{5. Columvi. Prescribing information. Genentech, Inc, 2023. Accessed November 30, 2023. https://tinyurl.com/34pr64u8}

_{6. Lunsumio. Prescribing information. Genentech, Inc, 2022. Accessed November 30, 2023. https://tinyurl.com/2atadckm}