Multidisciplinary Approach is Key to Managing Belantamab Mafodotin–Associated Keratopathy in Myeloma

Sagar Lonial, MD, FACP

Keratopathy, an ocular toxicity associated with treatment with belantamab mafodotin-blmf (Blenrep), is an adverse effect (AE) of interest for both oncologists and patients with multiple myeloma, and management is often dependent on a strong multidisciplinary approach involving ophthalmologists, according to Sagar Lonial, MD, FACP.

“Building that partnership [between oncologists and ophthalmologists] is key, as well as maintaining that open line of communication because sometimes they do not know what you are looking for,” Lonial said. “If you talk to them and say, “visual acuity is pretty good, tell me what you are seeing,” you can have that back and forth that helps the patient get the optimal care.”

In an interview with OncLive^®, Lonial, chief medical officer of the Winship Cancer Institute of Emory University, professor and chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine, and Anne and Bernard Gray Family Chair in Cancer at Emory University School of Medicine, discussed strategies for managing belantamab mafodotin–associated keratopathy in patients with multiple myeloma.

OncLive^®: Could you speak to the differences between mild to moderate and severe keratopathy associated with belantamab mafodotin treatment?

Lonial: One of the things that we are really excited about in the management of triple-class refractory multiple myeloma is the availability of an off-the-shelf BCMA-targeted approach like belantamab mafodotin. Obviously, there is efficacy [associated with this treatment], but balanced with efficacy is safety. One of the unique adverse effects [AEs] that we see [with this treatment] is keratopathy, which is basically the development of microcysts on the cornea. Now, the good news about these microcysts is that they are reversible, and they resolve over time. More importantly, it is the evaluation of these microcysts that really is crucial in understanding the severity.

Mild- to moderate- typically means that there are fewer impacts on visual acuity, and that the number or density of the microcysts, particularly in the central part of the cornea, are fewer than severe- keratopathy. The worst form of keratopathy is the development of an ulcer in the cornea, which in phase 2 DREAMM-2 trial [NCT03525678], only occurred in 1 patient and did completely reverse and resolve. In fact, that patient was re-dosed. It is important to recognize that that grading system is something we are dependent on ophthalmologists to do with us. Moreover, it has to do with an on-target effect associated with the antibody-drug conjugate, as opposed to the targeted BCMA.

What are some best practices for managing this toxicity?

If you have never given belantamab mafodotin before, you want to establish that relationship with an ophthalmologist [or optometrist] even before you give that first dose, because you are going to need that close interaction. If you live in a small town and do not have access to lots of ophthalmologist, optometrists can do this exam as well. One of the first important things to recognize is that this is not a complicated exam. The chair of pphthalmology at the University of Chicago mentioned to the Oncologic Drugs Advisory Committee [ODAC], that this is something every first-year optometrists or ophthalmology resident can do in the first week of their residency or training. It is not a complicated exam, you just need to be able to quantify what you are seeing, and then grade it. There is a very nice descriptor on the form that can help the ophthalmologist do that.

Could you speak to the importance of getting ophthalmologists involved early in the treatment journey? How often visits should be scheduled?

Ophthalmologists need to see a patient prior to first dose. It is important to establish that relationship even before because when you are ready to go, you do not want to wait 3 weeks to get them in to see an ophthalmologist. Building that relationship and suggesting to the ophthalmologist that you may need a slot with an urgent review is [optimal].

You can even do the training, and the ophthalmologist can do some of that simple stuff that can be done in advance so that when you are ready, you can turn it around within a week. That week is usually the turnaround time that I look for, mostly because it takes a week to get precertification from the insurance companies, as well. If you can get an ophthalmologist to set the exam up in a week, that gives you time to be ready to move.

The other thing that we do as part of our practice is schedule out visits with the ophthalmologists every 3 weeks for approximately 3 months. That way you do not have to worry about finding that slot, it is already established and ready to go.

Could you speak to the importance of multidisciplinary management of AEs experienced with treatment?

One of the things that we are discovering is that while the management of AEs of traditional chemotherapy have always been the purview of the oncologist, as we get more and more targeted agents, we need to broaden that family a little bit. An example of that, for instance, is cardio-oncology. We have many drugs that we use, both in solid tumors and hematologic malignancies, that affect the heart. Having a cardio-oncologist as part of the team is critical. If you talk to our melanoma colleagues, or anybody that gives a TKI, dermatology becomes an issue. As such, we now have dermatology-oncologists that really focus on those manifestations.

Ophthalmology is being added to that mix now, and urology is another category that we add as well. The key is understanding how big the family needs to be to help you deliver the optimal care. One of the things that we are focusing on as a myeloma center, and as a cancer program, is how to make sure that we streamline that process for patients in advance and set those relationships up early.

How are dose modifications being used to manage this AE? How about stopping and restarting the drug?

There are a lot of patients and I a lot of oncologists that are a little nervous about this ocular toxicity, because it is not something we have dealt with before. Again, to bring it back to the ODAC discussion, there was a genitourinary oncologist who was on the on the committee who detailed how they figured it out in genitourinary malignancies, because they have a drug that has corneal toxicity, and hematologist should be able to figure it out too. That is the truth, the more we do it, the more we become comfortable with it.

It is okay to miss doses. That is the other important message. It is not uncommon to dose somebody every 6 weeks instead of every 3 weeks. That is okay. The half-life of the antibody is so variable, that there may be patients who go 9 or 12 weeks without a dose, but still hold or deepen their response. We need to allow the patient to feel comfortable with the idea that we are trying to make sure we optimize vision, which is important for them. At the same time, the drug may be continuing to work, so do not get hesitant or anxious about missing doses. Many patients miss 2 or 3 doses and still have long durable responses.