Role of Belantamab Mafodotin In the Treatment of Heavily Pretreated RRMM

EP: 1.72-Year-Old Man with Heavily Pretreated RRMM

EP: 2.Treatment Options for Heavily Pretreated RRMM

EP: 3.The DREAMM-2 Trial in RRMM

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EP: 4.Role of Belantamab Mafodotin In the Treatment of Heavily Pretreated RRMM

EP: 5.Current Status and Future Directions in RRMM

Sagar Lonial, MD, FACP: As we evaluate how belantamab mafodotin [belamaf] fits into our current treatment paradigm, the FDA indication is for patients with 4 or more prior lines of therapy who are basically resistant to PIs, immunomodulatory agents, and an anti-CD38 antibody... I consider belamaf for most [of these patients] unless there’s a potential contraindication that may make the use of belamaf more challenging. Given that keratopathy represents the most common adverse event, you need to explain to patients that there is a chance that [it can affect] their vision or ocular comfort. If you look at patients in DREAMM-2 [NCT03525678], 72% of patients had some form of keratopathy. That’s an exam finding. That is not a clinical finding, meaning patients don’t complain of keratopathy. What they complain about are things, such as dry or itchy eyes, that represent the most common reason for keratopathy. Some patients may experience changes in visual acuity. If you look at data from DREAMM-2, only 18% of patients had significant changes in visual acuity and only 3% of patients had to come off the drug because of significant changes in visual acuity. It’s important to separate the impact of keratopathy by an ophthalmologist using a slit-lamp exam vs clinical impact of keratopathy, which occurs in a much smaller number of patients. From a practical perspective, there are some [treatment] strategies, but what we saw from Dr [Rakesh] Popat at his ASH [Alliance for Shared Health] presentation was that the quality of life data suggested there was no significant decrement in quality of life for patients who were treated with belamaf. This speaks to the fact that these are patients who have had a lot of treatment coming in. They understand the resistant nature of their disease, for the most part. Again, [approximately] 18% did not have significant impacts on visual acuity, their ability to drive, or their ability to read. From a dosing and frequency perspective, the treatment is given every 3 weeks, which means an office visit once every 3 weeks. The added wrinkle with belamaf is that you need an exam from an eye care professional, either an ophthalmologist or an optometrist, within 48 to 72 hours of each dose of belamaf. At our center, for instance, [patients will] see ophthalmology in the morning, us in the early afternoon, and if everything is OK, then we’ll dose them in the afternoon. The infusion is relatively well tolerated. It’s easy and quick to give... The next most common set of adverse events were hematologic, which were of much lower grade and severity than the keratopathy pieces that continue to be 1 of the more prominent adverse effects of this drug. From a dosing perspective, again, it is relatively easy to give. The office visits are relatively rare and the biggest problem is partnering with an eye care professional at the outset.

When it comes to ocular toxicities associated with belamaf, there are a couple of key pieces of information that patients and providers should be aware of. The first is that it does not occur in everybody, and an exam finding doesn’t always translate into clinical decrement in function. Although we do worry about changes in visual acuity, for many patients—particularly patients with myeloma who’ve been on a lot of steroids and may have cataracts that can interfere with vision, as well—it is important to put the potential in front of the patient and have them understand that although this could be an event, only 18% of patients in DREAMM-2 actually had visual acuity changes of 20/50 or greater. The majority of patients did not have that significant adverse event. What we also learned from DREAMM-2 is that corticosteroid eye drops used with cytarabine, for instance, do not offer significant benefit in risk reduction. This is an effect of MMAF, and steroids alone don’t address or mitigate the impact of that adverse event. We also learned that lubricating eye drops are quite helpful and are included in the pack for many patients who are starting on belamaf. That’s important because dry or itchy eyes may be 1 of the more common adverse effects that they experience. Having them use those lubricating eye drops frequently can be very helpful in minimizing the long-term potential issues with belamaf. The other thing we know about belamaf-associated keratopathy is that it is reversible. In almost every patient in DREAMM-2, it reversed, and in those whom we don’t have documented evidence of reversal, it’s because they came off with refractory myeloma and either withdrew additional follow-up or died in the context of refractory myeloma. Every patient that we do have a good follow-up on has had improvement and complete mitigation of their ocular issues. This does not cause long-term or permanent damage to the cornea. It is a reversible finding in patients, in general. These 2 things, along with partnership with your eye care professional, help you to manage and mitigate the potential toxicity. One of the other pieces that is important is the idea that just because you have to hold a dose because of the presence of keratopathy doesn’t mean that you’re going to lose control of the disease. If you look at the patients who had doses held of belantamab [during] therapy, only 20% or fewer had progression during the time of dose holding. That’s important because, unlike cytotoxic chemotherapy where if you hold the dose you often lose control, the half-life of the antibody can be so long you don’t actually lose control. In many patients, you deepen the response over time. You may learn that a patient may only need to be dosed every 6 weeks in instances where they keep having to miss that every-other-dose scheduling and their keratopathy continues to improve with each subsequent cycle of therapy.

Transcript edited for clarity.

A 72-Year-Old Man with Heavily Pretreated, R/R Multiple Myeloma

Initial Presentation

• A 72-year-old man diagnosed with multiple myeloma 4.5 years ago returns for routine follow up
• Treatment history:
  • Initially treated with VRd for 12 months, followed by lenalidomide maintenance 15 mg daily; stable disease lasting 36 months
  • Rechallenged with VRd, stable disease lasting 20 months
  • Subsequently switched to KPd, achieved a partial response lasting 15 months
  • Started DVd; follow up at 12 months showed M protein increase by 0.5 g/dl; patient continues to feel well 
• Currently, 3 months after his last visit, he returns to the clinic complaining of increased muscle weakness, fatigue and bone pain
• PE: new bony tenderness appreciated on ribs, bruising, mild bleeding of the gums

Clinical Workup

• Labs: Hb 8.8 g/dL, calcium 10.2 mg/dL, LDH 160 U/L, creatinine 2.1 mg/dL, albumin 3.0 g/dL, b2 microgloblulin 4.9 mcg/mL, serum M-protein 4.2 g/dL, lambda free light chains 4.1 mg/dL
• HBV negative
• Skeletal survey and MRI revealed stable lytic bone lesions in the left hip, pelvis and L2 vertebrae and new lytic lesions on the ribs 4 and 10 on the left side
• Bone marrow shows 70% plasma cells IgG k
• FISH: t(6;14) (p21;q32) at diagnosis; new del(17p)
• Diagnosis: R-ISS stage II MM
• ECOG 1

Treatment

• Initiated treatment with belantamab mafodotin