Administering Step-up and Treatment Doses of Bispecifics in MM


A brief review of bispecific antibody dosing strategies in multiple myeloma to improve patient outcomes and address concurrent adverse events.


Ajai Chari, MD: This is a good time to just review teclistamab dosing. Robert, walk us through how teclistamab is given at the bedside.

Robert Mancini, PharmD, BCOP: One important thing we’re seeing with pretty much all the commercial bispecifics is the requirement of step-up dosing. The big reason is these are bispecific T-cell engagers, which means we’re engaging the T cells to kill our target—in this case, BCMA-expressing B cells. When T cells are attacking those B cells, they’re releasing cytokines. That’s why we get cytokine release syndrome [CRS]. We want to slowly work into that.

What you’ll see is a step-up dosing. The first dose is a very small dose. It’s only 0.06 mg/kg given on day 1. The next dose, which is step-up dose No. 2, is going to be slightly larger, 0.3 mg/kg. That’s typically given on day 4. However, if you look at the package insert, there’s some leeway in terms of when you can give that second dose. You’ll notice the superscript B. That means that step-up dose can be given 2 to 4 days after step-up dose 1. Many institutions, ours included, are moving toward this. I’ve talked to many others who will do the second dose on day 3 to shorten the time they may be in the hospital during that ramp-up phase. As long as they’re doing OK, of course. If they have CRS after dose 1, you’re not going to keep going until that’s resolved. That’s where your step-up dose 2 comes in. The third dose, which is the first treatment dose or first full dose, at 1.5 mg/kg, is going to be given on day 7. That can be adjusted the same as that second step-up dose. The first treatment dose, superscript C in this case, can be given 2 to 4 days after step-up dose 2 if they’re tolerating it.

Rather than a 1, 4, and 7 in all situations, you may see a 135-type schedule following that dose ramp-up. Once you get that first treatment dose in, beyond that, you’re going to give this weekly. One week after that first treatment dose, you’ll continue at the same dosage, 1.5 mg/kg once weekly. You’ll continue on that weekly until progression or unacceptable toxicity.

One thing that’s important to note is premedication for these doses, especially in the ramp-up phase. If you look at the recommendations in the package insert for premedication, you’re going to see that they’re recommending a dose of a corticosteroid, usually dexamethasone at approximately 16 mg, or the equivalent an H1 antagonist such as diphenhydramine and an antipyretic such as acetaminophen. It’s recommended that we give those prior to each ramp-up dose. Then you can drop that. I’m curious about your experience and how often that gets dropped. You can drop that starting with cycle 2, day 1, assuming the patient did fine through those first 3 doses.

Ajai Chari, MD: Thanks, Robert. That’s very helpful and clear. Kiah, I have 2 questions. First, you’ve been primarily involved with research. There wasn’t a research pharmacy ready to mix a drug on a weekend, so that affected the schedule. But when you’re consenting patients, what do you tell them to expect in terms of the duration of hospitalization? Do you have preferred days of starting a priming dose?

Kiah Purcell, NP: We definitely have preferred days of starting. If we know that with this drug CRS is going to happen on day 1 or day 2, then I’d prefer to set it up so we don’t have to have 4 days between dosing. If we’re starting on 1, then I’d consider a Friday or Tuesday start to minimize the time in the hospital. Although with Friday, you have to think about what the staffing is going to be like on the weekend and if it’s safe to have someone with CRS on the weekend—will there be enough trained people? I always tell the patient longer than shorter. If it’s days 1, 4, and 7, then I’m going to tell them days 1, 4 ,and 7. Even though we can administer the second dose a little bit earlier, I plan on this because they’re always happier to get out earlier if we can. If it’s safe, they haven’t had CRS between doses, they’re tolerating well, and we can discharge them a little earlier, then that’s always better. I always have them expect the longest.

As far as step-up dosing with premedications and restarting after a break, in general, we’ve found that if they’re tolerating treatment at the full dose without CRS, they usually do OK when we discontinue the premedications. When we discontinue the premedication, we have a lot of patients who just get teclistamab subcutaneously no premedications. If they’ve been tolerating it, they have no problem. Regarding discontinuing at cycle 2, as long as they’re tolerating it, I would think about it. If they’ve had postdose fevers, rashes, or any other adverse effects that we could attribute to the drug, then we’d consider keeping it on for another few doses until they’re tolerating, especially since they’re going home at that point. We don’t want them having issues at home. Also, if we have a long break in treatment, we consider restarting premedications as needed depending on how long the break is and what grade CRS they had originally.

Transcript edited for clarity.

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