Ola Landgen, MD, PhD

Ever-Expanding Indications for Daratumumab in MM

Practical Management of IV Daratumumab in MM

Exciting Subcutaneous Formulation Approval in MM

Clinical Impact of SubQ Daratumumab for Multiple Myeloma

The Impact of COVID-19 on Patients With Multiple Myeloma

Videos

How the recent FDA approval of the subcutaneous formulation of daratumumab in multiple myeloma will affect patients and oncologists from practical and clinical standpoints.

Role of Novel Subcutaneous Daratumumab in Multiple Myeloma

The COVID-19 [coronavirus disease 2019] pandemic has clearly impacted everything, including the care of patients with multiple myeloma. The changes are more practical. We don’t really see that the prognosis is very different for patients with myeloma compared with what we have seen in the general population. That’s very good news. We have been very cautious and careful across the board. All the institutions, we talk to one another all the time. We have been using fewer doses. Instead of giving weekly doses and then dosing every other week, if the regimen has such a dosing schedule, we have tried to move to monthly infusions more quickly to try to skip a few steps. If possible, we have tried to use more oral drugs versus IV [intravenous] or subcutaneous [SQ] drugs. Of course, for newly diagnosed patients or patients who have an active relapse, combination therapy is still much more powerful, so we obviously would prefer that. But then we will go toward a less intense regimen to spare the patients from unnecessary visits.

We have cut back on biopsies; there are no bone marrow biopsies. And also imaging; there are no PET [positron emission tomography] or CT [computed tomography] scans or other types of imaging, unless there is really a strong reason. Typically, in newly diagnosed patients, we would check for MRD [minimal residual disease] status after 6 cycles. Now we would hold off with that. We are waiting for COVID-19 to calm down before we start doing these things again. We also stay away from those combination therapies that are highly cytopenic, and that’s typically in the relapsed/refractory setting. Using all the chemotherapy drugs that would make the patient a candidate for transfusions is not what we want.

The patients would be immunosuppressed, exposed to a lot of risks, and there would be need for platelet and blood transfusions, which we try to save because there is a shortage of blood products.

I think very importantly, we have stopped the entire program for transplantation. This is supported by the ASH [American Society of Hematology] Guidelines that very clearly state no more bone marrow transplants in the setting of COVID-19 for patients with myeloma. This is with the exception of patients who have a lot of aggressive disease, for whom there are no other options. But those patients are few and far between given all the other options we have. ASH says to hold off on the collection of stem cells, so that’s also implemented across the board.

Using modern combination therapy and switching to maintenance, we use carfilzomib, we use bortezomib, we use lenalidomide, we use pomalidomide, we use daratumumab, and we use dexamethasone. We use all those drugs, but we are just cautious and try to minimize the unnecessary visits. We do most of their care, I would say 99% of their care, with telemedicine at the current time, but we are also planning to go back and start seeing patients in the clinic in the coming weeks.

In the current setting of COVID-19, daratumumab is becoming an established standard of care in the newly diagnosed setting in combination with lenalidomide and dexamethasone for nontransplant patients and emerging in combination with RVd [lenalidomide, bortezomib, dexamethasone] or KRd [carfilzomib, lenalidomide, dexamethasone] for transplant candidates. This is already an established standard of care for patients with relapsed disease given CASTOR, POLLUX, and other studies. We already have it in that setting, but the SQ administration of daratumumab would make it an even more attractive regimen. It will increase its use in all these different settings because it’s quicker and easier to give.

Access to a subcutaneous [SQ] version of daratumumab will make daratumumab even more attractive for any indication. I could see that it could be partnered even more so with drugs for up-front therapy, given that it is FDA and/or NCCN [National Comprehensive Cancer Network] Guidelines–approved. In the relapsed setting, it also gives daratumumab an upper leg compared with other drugs because it’s so easy and so well tolerated. It also is efficacious. I think that the use of daratumumab as an extended dosing regimen in the fashion of a maintenance therapy will probably become more popular. It’s not being developed as a maintenance drug, but it’s very likely that daratumumab could take the role of a continued injection over time where patients could come in and get an injection and that would be all. We will see exactly where that’s going to land. But I think the SQ route really gives daratumumab a very strong upper leg.

With daratumumab being FDA approved as a subcutaneous drug, I think that should be immediately implemented and should replace the intravenous [IV] drug. It really has a role in any setting, anything from the newly diagnosed and early disease to later stages of disease, based on the NCCN Guidelines and the FDA label. It just gives us access to a good drug for more patients because it’s easier to administer and we can pretty much use it anywhere. You don’t have the long infusion at the beginning, which we used to have with the IV formulation.

How will the subcutaneous administration route impact patients and the whole clinical procedure compared with the IV formulation? It’s quite obvious. If you have a drug that can be given as a shot, everyone likes it. The patient loves it. It’s a much shorter visit. The chemotherapy nurses like it because the patient can sit in the chair, you give an injection, and then you’re done. The overall institution likes it because you can reduce the number of chemotherapy chairs and get the work done. Of course, you still must take care of the patient. You have to monitor and make sure everything is safe, but it is a much more feasible way of using this drug.

The administration schedule for the subcutaneous version of daratumumab is the same as the IV administration. According to the FDA label, it’s once a week for 8 doses, then every other week for 8 doses, then once a month, or every 28 days to be exact. It’s the same for both of them. The subcutaneous administration has a fixed dose. The IV dose is 16 mg/kg body weight.

Daratumumab being approved for administration as a subcutaneous [SQ] drug is a huge step forward for the myeloma field. This really gives every patient access to daratumumab. There has been some hesitation in smaller offices that don’t treat so many patients with daratumumab, given that the administration of the monoclonal antibodies as infusions took an extended window of time, at least with the first dose. There was a little bit of a barrier, but once you got up and going, it could be done in a few hours or even as rapid infusions in 90 minutes. With the subcutaneous administration, you start off really fast. It’s only an injection, so it’s a 5-minute procedure. You still will have to monitor the patient afterward, but the fact that it’s a very quick injection is of course fantastic for patients. It makes it much more feasible for doctors’ offices.

The data show, from the studies that have been presented so far, that the efficacy seems to be virtually identical compared with the IV [intravenous] drug. These are single-drug studies comparing SQ with IV. We don’t yet have a lot of data from combination strategies, but there’s no reason to believe that they wouldn’t be the same. I assume that once the drug is approved as a subcutaneous drug, it will move on in all the combinations. I think another huge benefit with the subcutaneous drug is the fact that the drug has fewer infusion-related reactions. With the intravenous drug, around 50% of the patients had an infusion reaction for the first dose and after that, it typically would never happen again.

With the subcutaneous drug, the data suggest that maybe 10% of the patients experience this. I do think there will be continued development when it comes to the premedication. It’s not fully known, but my prediction—based on my clinical experience for many years treating patients with myeloma with different types of drugs, and also treating other hematologic malignancies—is that premedication with steroids can probably be cut back. I think the antihistamine premedication can probably be cut back. The overall experience with daratumumab will be even more gentle beyond the fact that it’s now an injection. We can cut back on the premedication, I would think. We will need a little more data to fully hammer this out, but that’s my prediction.

At our program at Memorial Sloan Kettering Cancer Center, we have used daratumumab extensively with the intravenous administration. This goes back years before it was FDA approved, on clinical trials. We have used it extensively after it was FDA approved as a standard-of-care drug. We are just about to open investigator-initiated studies using the subcutaneous administration. With the FDA approval for the drug, we will obviously switch the entire program from IV to subcutaneous administration within days after the FDA signs off on all the papers.

The subcutaneous dose will definitely reduce patient time in the office, although we don’t know to what degree we need to monitor patients after the first dose with the subcutaneous drug. The data suggest that instead of 50% infusion-related reactions, which we see with IV administration, the SQ administration has about 10% infusion-related reactions. We don’t fully know what the time window should be for monitoring. I think our practice, located in the heart of New York City, will maybe let patients stroll around the city rather than sitting and waiting for many hours. But I could also see that we could potentially have patients waiting in the building instead of sitting in the chemotherapy suite and waiting for hours, as we have done when we have given the intravenous infusion. I think we will learn as we go. I do predict that we probably will loosen up on these rules and procedures going forward. To begin with, we will probably have the patient around for a few hours. After the first cycle, I could see that it will probably be a very short visit. But this is to be investigated further.

Ola Landgen, MD, PhD | Authors

Articles

Role of Novel Subcutaneous Daratumumab in Multiple Myeloma

The Impact of COVID-19 on Patients With Multiple Myeloma

Clinical Impact of SubQ Daratumumab for Multiple Myeloma

Exciting Subcutaneous Formulation Approval in MM