The Intravenous Administration of Monoclonal Antibodies
INSIGHTS FROM: AJAI CHARI, MD, MOUNT SINAI HEALTH SYSTEM; DANIEL VERINA, NP, MOUNT SINAI HEALTH SYSTEM
Wednesday, May 13, 2020
Ajai Chari, MD: Hi, my name is Ajai Chari. I’m a professor of medicine at the Icahn School of Medicine at Mount Sinai in New York. Today I’m privileged to have joining us one of our most seasoned NPs [nurse practitioners], Daniel Verina. Together we’re going to be covering daratumumab, the intravenous and subcutaneous formulations, and what’s new and exciting. Daniel, welcome. Thanks for joining me.
Daniel Verina, NP: Thank you. It’s my pleasure.
Ajai Chari, MD: Let’s get things started. I think to set the stage, obviously we know daratumumab is a CD38 monoclonal antibody. It’s approved for myeloma in several different indications and combinations. In the newly diagnosed setting for transplant-eligible patients, it’s actually approved in combination with VTd, or bortezomib, thalidomide, and DEX [dexamethasone], so DARA/VTd [daratumumab with bortezomib, thalidomide, dexamethasone]. For the transplant-ineligible population, it’s also been approved in combination with lenalidomide and dexamethasone as part of the MAIA study, and also with VMP [bortezomib, melphalan, prednisone] as part of the ALCYON study. All of these have shown that the addition of daratumumab has led to significant improvement in not only response rate but progression-free survival [PFS].
I think one of the other interesting things about this front-line setting is there’s always this question of if you use your drug early, what might happen? And I think an important additional statement to that point is the ALCYON data from ASH [the American Society of Hematology annual meeting] 2019 was updated to show that the addition of daratumumab not only improved response and PFS [progression-free survival], but also overall survival. So I think this concern about using drugs early and potentially getting more aggressive relapse has not been borne out, particularly for the transplant-ineligible population, where you don’t always get a chance to salvage these patients.
And then briefly, in the relapsed setting, daratumumab is also approved in combination with lenalidomide and dexamethasone, and bortezomib and dexamethasone as part of the POLLUX and CASTOR studies. This is with at least 1 line of prior therapy. And then it’s approved in combination with pomalidomide and dexamethasone for at least 2 prior lines of therapy, including a PI [proteasome inhibitor] and an IMiD [immunomodulatory drug]. And finally it’s approved as monotherapy for patients who’ve had at least 3 lines of therapy, which include a PI or IMiD. Those are the current uses of daratumumab, and there are a lot of other exciting studies.
Now I’ll throw this to Danny. So, Danny, you agree, a lot of options to use daratumumab, and maybe you could walk us through what it’s like to give daratumumab currently, which is in the intravenous formulation.
Daniel Verina, NP: Absolutely, thank you. Yes, I think it’s a great option for many of our patients, starting even in newly diagnosed, and like Dr Chari said, even salvage and in the relapsed setting. Because it is a monoclonal antibody, I think many of our patients are concerned about different testing and different adverse effects that they’re going to see. When we speak to our patients up front, we really talk to them about doing normal laboratory tests. You’re going to get your complete blood checked, your CBC [complete blood count], your CMPs [comprehensive metabolic panels]. Interestingly enough, they did find in later data that there was a reactivation of hepatitis B, so now we are testing all patients for hepatitis panel and hepatitis C up front before starting daratumumab, if they need any type of medical interventions prior to starting the medication itself.
Also, we can talk about it a little bit later, is that because daratumumab is a monoclonal antibody, it does adhere to the CD38 receptor that’s located on erythrocytes, and you can interfere with some type and screening of blood. So most patients should have a type and screen drawn prior to their first dose, so that their blood banks can monitor, and know that to be in their control, and if they have antibodies in the past.
Interesting also is because it is an IgG [immunoglobulin G] kappa, it can cause interference with immunofixation electrophoresis [IFE]. Why that becomes important down the line is when you’re trying to say if a patient truly is in complete remission or in a very good partial remission, vgPR, knowing this up front is important. So patients who are IgA or IgM, it really has no bearing on it. But really you’re IgG kappa. So there are 2 tests available. There’s a daratumumab interference assay that is available and also mass spec [spectrometry] on the local level. So if the IFE is there and we want to find out whether it is interference from the drug itself, or does the patient still have a very fine amount of disease, that’s also important.
*Note: Subcutaneous daratumumab is now approved in the United States and Europe.