Dosing and Toxicity: Challenges in AE Management of Belantamab Mafodotin for R/R Multiple Myeloma

Peter Voorhees, MD

DALOVISIO: I’d say in the small handful of patients [for whom] I’ve used it, it follows the clinical trial data pretty closely as far as the keratopathy incidence, response rates, and adverse event [AE] profile. I’ve been feeling like it’s been sold correctly or advertised as is.

VOORHEES: Have you found that you’ve been holding the drug frequently for the eye-related AEs?

DALOVISIO: Yes, but in my responders what I’ve found is that disease is usually maintained [under] control until the keratopathy improves enough to [re-dose] [Tables 1 and 2^1,2]. I feel it’s manageable. It can be frustrating for the patients but manageable in the context of what your other alternatives are in late-line therapy.

VOORHEES: [For others], what are the barriers to your use of this agent? Is it just that you don’t [treat] these triple-class refractory patients? Is it trepidation regarding the keratopathy profile that’s been reported? Is it the logistical challenges with regards to ophthalmologic evaluations?

FEAGIN: I’ll be honest, I have some trepidation about that and about the ease of getting [patients] into ophthalmology

FEAGIN: We have a fair number of ophthalmologists in the cities, but same-day appointments or weekly appointments and that kind of thing, I’m not sure I’d be able to get that. The other thing is that when I have patients like this, I usually try to convince them to go see a transplanter and see what their options are. Usually before we get to this point, I at least have an opinion somewhere else.

GILL: The frequency of ophthalmologist appointments can be a barrier, for some of my patients, just getting them in before each dose.

CHARBONNET: How often do you need slit lamp exams? Is it every 2 cycles, every 6 weeks?

VOORHEES: With the REMS [Risk Evaluation and Mitigation Strategy] program, you need a baseline examination within 3 weeks of the first dose, and then you need to have an eye exam before each subsequent dose.³ And that eye exam has to be at least be 1 week beyond the last dose and within 2 weeks of the next dose.

CHARBONNET: So it’s almost every 3 weeks that they’re going to need the eye exam.

VOORHEES: Yes, that’s exactly right. Generally, what I’ve done is I try to get it within a week of the next dose. I try to get it in relatively close proximity, so I can see the full extent of changes from the previous dose. Is anyone familiar with keratopathy or feels comfortable managing it?

DALOVISIO: We’ll use lubricants and artificial tears, but largely I rely heavily on the ophthalmologist. I know the grade is what you base your holding and dose reductions on [Figure 1⁴].

VOORHEES: Are you able to read the reports that come?

DALOVISIO: [I receive] the Snellen chart for the belantamab REMS. I’ve learned enough to get that done. But I generally try to touch base with an ophthalmologist before I redose just to clarify the [grade of] keratopathy.

VOORHEES: Have you had any challenges interfacing with the ophthalmologist or the eye care professionals for your patients in getting them plugged in to have that eye exam before each dose?

DALOVISIO: We’ve been pretty lucky. We had a fair number of patients with myeloma at our institution, so we actually approached the ophthalmology department and got somebody to [participate]—so they’ve been very helpful and gotten really good at it too.

VOORHEES: For those of you that are going to increasingly use this agent, having a specific group of eye care professionals with whom you work can be quite valuable because it’s a learning curve for them as well. And the more experience they gain, the better they get at doing it.

DALOVISIO: Optometrists can do it too, I believe.

VOORHEES: It can be any eye care professional.

FEAGIN: When I’ve had other eye emergencies, sometimes it’s been challenging to get [a patient] seen fairly quickly for patients on other drugs. They’re just complications of life…. The key is the relationship with a single group who will give you a little bit of preferential treatment or save you some slots. That’s got to be the key to getting this done before every cycle.

VOORHEES: Yes, I agree. Just based on my own experience, we’ve been fairly fortunate because we’ve got a number of ophthalmologists with whom we work. But for a lot of subspecialties, it may take a long time to get that first visit in place. Once they’ve got their foot in the door getting the exam, it becomes much easier with each dose because the patient is in the system and they can schedule them in advance, so it does get easier.

As far as the support services and resources, GlaxoSmithKline does have those available. They can also help the hematology/oncology team identify an eye care professional to refer the patient to. They can provide the patients with artificial tears to help them as they’re on treatment, so be aware of that. They can make transitioning the patients onto belantamab mafodotin a lot easier.

DALOVISIO: I talk to the patients about it, especially [because] I know a lot of patients can lose their ability to write or drive and [lose] their transportation or their occupation. I talk to them about those things before I use it. But I also pitch in the context of lack of other options outside of trials.

VOORHEES: Patients get keratopathy. It’s quite common. But oftentimes, it occurs without symptoms. Not everybody gets visual acuity changes that are severe, and in fact, only 3% in the DREAMM-2 trial [NCT03525678] actually discontinued belantamab mafodotin permanently because of keratopathy issues [Figure 2].⁵ With dose holds and dose reductions, they were able to navigate patients through treatment.

There are also baseline exams that need to be done within 3 weeks before the first dose and at least 1 week after and within 2 weeks prior to the next dose. It’s advised that patients use preservative-free eye drops at least 4 times a day. I usually tell patients to do it hourly while they’re awake and avoid the use of contact lenses while they’re on belantamab mafodotin.

The patients need to be advised that if they do develop keratopathy with clinically significant visual changes, it may impair their ability to drive and read, so they have to have that support system in place—so if they’re not able to drive, someone can do it for them. If reading is a very important aspect of their life, there are potential quality-of-life issues that come into play, so these patients need to be counseled about these things before dosing.

CHARBONNET: I like the fact that it doesn’t really have any major hematological AEs, but I think the ophthalmology issues would be an excluding factor for us. We’re [in a town with a] population of 40,000, and we’ve gone from 3 ophthalmologists to 1. I know optometrists can do the slit-lamp exam, but you’d have to trust them. And until we’re using similar drugs in other disease classes, you have to have somebody you can trust. I think right now I’m going to be excluded. I don’t think I can get somebody in every 3 weeks with the eye doctor in our situation. I think until that resolves, this is going to be on hold and then just [referring patients to] my tertiary center.

VOORHEES: So if you had a patient that was going to the local Walmart and having the optometrist at the Walmart doing your visual acuity assessment and slit lamp exam before each dose, does that give you the level of confidence that you want?

CHARBONNET: [Our local] Walmart optometrist is pretty decent. [But] since my experience is nil at this point, for the first few [patients], I’d want to [use] an ophthalmologist instead of the optometrist just to hold my hand until my confidence level is up. I think that’s a problem that’s probably holding it off because, otherwise, the AEs for fourth-line treatment look very promising.

VOORHEES: The only other thing that I’ll point out too is that this is an off-the-shelf product. Yes, you need an eye exam, but it is off-the-shelf and you can gain access to it much faster than you can CAR T-cell therapy, which is another consideration. So if you have a patient who’s progressing very rapidly, they’re not going to have the luxury to get scheduled for apheresis, undergo T-cell manufacturing, and then get dosed subsequently.

ASHRAF: I think I’ll be using it, especially if an optometrist exam is enough. It will be easier. I didn’t know that.

FEAGIN: I may just start fostering my relations with ophthalmology [groups] and identify some physicians who are willing to integrate these patients from my practice in their group.

VOORHEES: I think that that’s a great idea. Again, GlaxoSmithKline can help you in this regard, and there is a training that [eye care professionals] go through [on] what they need to do as far as the exam is concerned and how to grade these patients, which could be quite helpful.

Combination strategies with belantamab mafodotin are being tested, and I think one of the more promising ones in the relapsed/refractory space is the [ALGONQUIN; NCT03715478] study that’s been led by Suzanne Trudel, MD, MSc, at Princess Margaret Cancer Centre in Toronto, Canada. They’re looking at pomalidomide, dexamethasone, and belantamab mafodotin in patients with relapsed/refractory multiple myeloma. At the doses that have been tested thus far, overall response rate is close to 90%.⁶ You’ll be seeing more data with combination strategies in the near future looking at different doses and dose schedules of belantamab in these combination strategies.

_REFERENCES:

_{1. Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study.Lancet Oncol. 2020;21(2):207-221. doi:10.1016/S1470-2045(19)30788-0}

_{2. Lonial S, Lee HC, Badros A, et al. Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study.Cancer. 2021;127(22):4198-4212. doi:10.1002/cncr.33809}

_{3. Risk Evaluation and Mitigation Strategy (REMS) document: Blenrep (belantamab mafodotin) REMS program. FDA. Accessed September 19, 2022. https://bit.ly/3GWBpFD}

_{4. Blenrep. Prescribing information. GlaxoSmithKline;2020. Accessed September 19, 2022. https://bit.ly/3Lsk8qK}

_{5. Lonial S, Nooka A, Thulasi P, et al. Recovery of ocular events with longer-term follow-up in the DREAMM-2 study of single-agent belantamab mafodotin (belamaf) in patients with relapsed or refractory multiple myeloma(RRMM). Presented at:62nd American Society of Hematology Annual Meeting and Exposition;December 5-8, 2020;virtual. https://bit.ly/3xCZ3Eo}

_{6. Trudel S,McCurdy A, Sutherland HJ, et al. Part 1 results of a dose-finding study of belantamab mafodotin in combination with pomalidomide and dexamethasone forthe treatment of relapsed/refractory multiple myeloma (RRMM). Blood. 2021;138(suppl1):1653. doi:10.1182/blood-2021-147101}