INSIGHTS FROM: AJAI CHARI, MD, MOUNT SINAI HEALTH SYSTEM; DANIEL VERINA, NP, MOUNT SINAI HEALTH SYSTEM
Wednesday, June 03, 2020
Ajai Chari, MD: I think another important thing before starting DARA [daratumumab] is the premeds [premedications]. Danny, what are the premeds that you typically like to give in patients before they start daratumumab?
Daniel Verina, NP: Usually up front, absolutely. But going back to your question of, if they don’t receive it at your center with the daratumumab, Janssen Pharmaceuticals Inc has also developed a card for patients to carry with them to let them know they are taking a monoclonal antibody. Because even if they were traveling somewhere else out of state and they had an emergency, that it states that they are on a monoclonal antibody.
Ajai Chari, MD: Good point.
Daniel Verina, NP: Premeds, I think, what are the adverse effects up front and we’re trying to mediate many of them going forward. With infusions, patients will get usually in the first dose, they’ll have everything pretty much IV, intravenously—corticosteroids, we’ll give them acetaminophen, and IV oral antihistamines up front. At our institution, we did use Singulair in our premeds to help prevent the cytokine release and the shortness of breath of bronchospasms. But we also use Pepcid, like an H2 [histamine type 2] inhibitor; that could be done. But in the clinical trials, they only really use the corticosteroid, the Tylenol, and the antihistamine. IV is appropriate for up front, but if the patient truly tolerates the medication, then they can all go to oral. Generally it’s given 1 hour prior to the starting of the daratumumab. I know in many institutions and in the community, if they’re taking oral, the option is 1 to 3 hours, so patients can actually take the medications at home and then go to their infusion center and receive the daratumumab. But I think that’s something you have to know, if the patient is oral adherent, and you know they’re really going to take those drugs up front.
Ajai Chari, MD: Premeds are super important. Maybe you could comment on, a lot of myeloma regimens obviously contain DEX [dexamethasone] already. You have these steroid premeds that are part of the daratumumab label, but then you’re also asking patients to get dexamethasone. How do you manage that?
Daniel Verina, NP: It is interesting that, yes, steroids are the backbone of what myeloma does. We will use them as premeds. Usually in the clinical trials they did use methylprednisolone. It was 100 mg for the first dose, and it dropped down to 60 mg. I think when patients are on long-term daratumumab, and if they’re in complete remission, we then at our institution are starting to pull the steroid out of the regimen if there’s no need for it. Because a lot of times our patients are much more mature in age and they have other comorbidities, so you’re dealing with hyperglycemia or other issues. So you can remove the steroids up front. They use methylprednisolone up front, but they also use dexamethasone because it was the backbone of the other medications, whether it was bortezomib or lenalidomide, so dexamethasone was substituted for it. Again, that’s also an option to switch from methylprednisolone to it.
An interesting thing to keep in mind, whether it’s premeds after their infusion, it was recommended to give steroids post-daratumumab because there was seen some delayed hypersensitivity up to 48 hours. So patients were given methylprednisolone for 2 days or dexamethasone the day after it. Again, in our institution, to be truly honest, if the patient truly does not have any adverse effects from it, we’ve removed the post-daratumumab dexamethasone, again, decreasing their exposure to it.
Ajai Chari, MD: Yes, I agree. I think the only caveat I would add would be that if somebody has a significant respiratory history, be it asthma or COPD [chronic obstructive pulmonary disease], since a lot of those patients may not have always been included in clinical trials, that’s probably the one subgroup of patients where, at least for the first dose, it may not be a bad idea to do the post-dose. But I think to be giving it for everyone, for the most part we don’t really see a lot of delayed reactions, and I think it’s probably not needed.
*Note: Subcutaneous daratumumab is now approved in the United States and Europe.