Belantamab Mafodotin in Relapsed/Refractory Myeloma Requires Multidisciplinary Effort

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Sanjay V. Patel, MD, FRCOphth, discusses the corneal-associated toxicities that can occur with belantamab mafodotin and the need for multidisciplinary management to optimally administer this agent.

Sanjay V. Patel, MD, FRCOphth

Belantamab mafodotin-blmf (Blenrep) has elicited significant responses in patients with relapsed/refractory multiple myeloma, but the corneal toxicities associated with its use will require a multidisciplinary effort between ophthalmologists and hematologist/oncologists, according to Sanjay V. Patel, MD, FRCOphth.

Belantamab mafodotin was approved by the FDA in August 2020 for use in patients with relapsed/refractory multiple myeloma who have received 4 prior therapies, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. The decision was based on data from the DREAMM-2 study, in which the antibody-drug conjugate elicited an overall response rate of 31% in those who received the recommended dose of 2.5 mg/kg.

The most common grade 3/4 AE reported by those who received the agent was keratopathy; this occurred in 27% of those who received the 2.5-mg/kg dose and in 21% of those who were given the 3.4-mg/kg dose. Because of this incidence rate, the FDA requires that patients, physicians, and infusion centers alike to participate in a Risk Evaluation and Mitigation Strategy (REMS) program to ensure the appropriate use of the treatment.

“There are several medications that can affect the cornea, but uncommonly, and so, a REMS program is not in place for those medications,” said Patel. “What's different here is that most patients on belantamab mafodotin are going to experience corneal toxicity [and some patients will be symptomatic]. As such, [this agent] really [requires] a new partnership between ophthalmology and hematology/oncology [to develop] a new way of trying to manage these patients.”

In an interview with OncLive, Patel, emeritus chair of ophthalmology at Mayo Clinic, discussed the corneal-associated toxicities that can occur with belantamab mafodotin and the need for multidisciplinary management to optimally administer this agent.

OncLive: How has the FDA approval of belantamab mafodotin impacted the treatment of patients with relapsed/refractory multiple myeloma?

PatelAs an ophthalmologist, I don't see patients with [myeloma] primarily, but I did see those on the DREAMM-2 trial because of their eye toxicities. Based on the patients I have seen, and with getting to know this drug, my understanding is that it offers those with relapsed/refractory myeloma an opportunity for prolonged survival. It sounds like it is an option that is very beneficial for patients.

Could you speak about the corneal toxicities that occur with this agent?

Some of the adverse effects (AEs) associated with this medication are very similar to other oncologic agents. However, this [agent] has a unique toxicity that is quite common: keratopathy, which is an abnormality of the cornea. This drug [can demonstrate] a toxicity in the corneal epithelium, so we would [refer to that] as a corneal epitheliopathy. I would say the majority of patients receiving this treatment will develop [deposits] in their cornea. For some patients, it can be a limiting factor to either further treatment if a dose reduction is not possible.

What we see is that these patients develop microcyst-like deposits in the cornea, many of [which] are scattered around the edge of the cornea. The cornea itself is an 11-mm circle; we do most of our seeing through the central 4 mm or 5 mm. These little deposits tend to occur in the periphery of the cornea early on and most patients wouldn't know that they're there because they're not symptomatic. However, we, as cornea specialists, can see them with a microscope.

Some patients will become symptomatic because if these deposits extend towards the center of the cornea where they cross the line of vision; [this results in] impaired vision or visual acuity. If they move to the center, that's when [a patient will] require an ophthalmologist or an optometrist to [advise] the hematologist or the oncologist on the grade of keratopathy which could result in the next dose being withheld.

Also, many patients will get dry eye syndrome, which is dryness in the tear film that covers the cornea and that can upset their vision or comfort; that is also something that you see with many other [cancer and non-cancer] medications. There are a couple of things happening here, but it's really those cyst-like deposits that are unique to this [agent].

What multidisciplinary effort will be required to adequately manage these AEs?

It's definitely [going to require] a multidisciplinary effort. With the agent only just being FDA approved, we haven't yet seen anyone on the drug yet [referred from our oncologists here]; the only ones I have seen were on the DREAMM-2 trial. However, I'm expecting them to be showing up any day now. Certainly, here at Mayo Clinic, we're fortunate because this is what we do; we work collaboratively with our colleagues in other specialties to coordinate patient care.

When a patient is put on this medication by a hematologist or oncologist, or if they're being considered for the medication, they need to be sent to an ophthalmologist or an optometrist for a baseline eye exam. We would see them to evaluate their whole eye: What factors are affecting their vision? What's the baseline? [Are there] other specific [factors] that already affect their cornea? What's the visual acuity?

Then, they'll be prescribed the drug, receive the drug on a 3-week cycle. Before each subsequent administration of the drug, they will need to see their eye care provider again. Each time we see them in subsequent visits, we're going to be checking the visual acuity, assessing their cornea primarily, and then grading any vision loss or corneal findings. We’re probably not going to see many findings in the first subsequent visit. [This effect is] more likely to [present] during the second subsequent visit, just based on what we saw in the DREAMM-2 trial.

We would assess our findings, and here, at Mayo Clinic, can electronically communicate that through the patient record to the hematologist and oncologist. In the rest of the world, that could be a bit of a challenge because you may have private groups of oncologists who need to work with private or independent ophthalmologists or optometrists who are going to be a little less familiar. [Therefore], they will need to establish chains of communication. That is essentially what needs to happen, per the FDA.

Could you expand more on what these eye exams look like?

The first exam would be a comprehensive eye exam, like when patients go to get their eyes tested. They’re going to have their vision measured on an eye chart. If they wear glasses or contacts, they often get a refraction. We would be doing a refraction in these patients to determine what their best corrected vision is with a pair of glasses.

The ophthalmologist or optometrist would then examine their eyes [through the use of] a slit lamp microscope. That provides us with a magnified view of the front of the eye, which is really where these [deposits] are going to be, in the cornea or the front window of the eye. At the initial examination, we would also look at other factors that may be influencing vision or other findings that may be important for us to know. We want to understand what their baseline looks like. The first exam could take a little longer than the others because we typically dilate the patients and then examine the front and back of the eye.

However, the subsequent exams will really be checking their best corrected vision; we want to know if their visual acuity has changed [since baseline]. We then assess their cornea, which is done with a slit lamp examination; there's no dilation involved there. Let's say a patient has no change or findings, then that's probably the end of the exam. If a patient has decreased vision and corneal findings are observed, they're probably related. If a patient has decreased vision, but the cornea looks good, we would [look further into this] by dilating them to see whether something changed in the back of the eye. We do not expect that with this medication, but other things can happen to patients. That's our role in this: To figure out whether it's a problem related to the drug or if there's something else happening that's unrelated to the medication.

Could you provide an overview of the REMS program?

As part of the DREAMM-2 trial, it became obvious that corneal toxicity is a common AE; [therefore], the FDA asked that a REMS program be implemented. Basically, this medication cannot be prescribed unless a patient has undergone a baseline eye examination. Subsequent treatments also cannot be given unless patients have an eye examination.

This is going to be new for this population of patients, but also for the physicians who manage them. Patients will be required to have eye examinations to receive this treatment. It will require communication and coordination between the eye care professional and the hematologist/oncologist. There's a structure in place that we, as the eye care professionals, don't get involved in, but my hematology colleagues need to be registered in that REMS program, [along with] the administering institution. As long as there's an eye examination on file and an order from the hematology specialists, then infusion center can administer the drug, but that's all coordinated through the REMS program. It's a coordinating mechanism to ensure these patients are getting their safety evaluation and not running into trouble with their vision.

Is there anything else you would like to touch on that we haven't discussed?

The vast majority of patients do not have permanent vision changes. Therefore, stopping the medication will result in improvement of the cornea and, if patients did experience a vision change, a return to baseline vision. Any changes that we see are reversible, but we do need to dose them according to what we see in the cornea.

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