# Belantamab Mafodotin Combination Therapy for Multiple Myeloma: Benefits, Eye Side Effects, and What Patients Should Know In the DREAMM-7 trial, patients had multiple myeloma that had worsened after at least one prior treatment. These patients lived longer without their disease progressing when they received a three-drug combination of belantamab mafodotin, bortezomib, and dexamethasone (called BVd). This was compared with a standard three-drug combination of daratumumab, bortezomib, and dexamethasone (called DVd). However, eye-related side effects were very common in the BVd group. 79% of patients had ocular (eye) adverse events. 84% had keratopathy (damage to the clear front surface of the eye) or changes in visual acuity (how clearly a person sees). Most of these eye events were grade 3 or higher, meaning they were serious. In a follow-up exchange of letters, the trial authors explained that these eye problems were managed mainly with temporary dose delays. The eye problems were not managed mainly with permanent discontinuation of treatment. 91% of patients who had a significant eye event were able to continue belantamab mafodotin after the event. # Belantamab Mafodotin Combination Therapy for Multiple Myeloma: Benefits, Eye Side Effects, and What Patients Should Know ## Table of Contents - Key Points - Background: Why This Research Matters - The DREAMM-7 Trial: How the Study Was Conducted - Key Findings: Benefits and Risks - Understanding the Eye Side Effects - The Scientific Debate: Concerns About the Data - The Authors' Response: How Eye Events Were Managed - Clinical Implications for Patients - Limitations of the Study - Recommendations for Patients and Caregivers - Frequently Asked Questions - Source Information ## Key Points - In the DREAMM-7 trial, BVd extended progression-free survival compared with DVd in patients with multiple myeloma that had worsened after at least one prior treatment. - Eye side effects were very common with BVd: 79% had ocular adverse events and 84% had keratopathy or visual-acuity events; most were grade 3 or higher. - In the trial, 91% of patients with a significant eye event continued belantamab mafodotin after the event, receiving a median of 8 additional cycles. - The median time to first eye event was 106 days, so eye monitoring should continue throughout treatment, not just at the beginning. - The 9% permanent discontinuation rate may change with longer follow-up, as the trial's median follow-up was shorter than its median progression-free survival. ## Background: Why This Research Matters Multiple myeloma is a cancer of plasma cells, which are a type of white blood cell found in the bone marrow. When multiple myeloma progresses after initial treatment, patients and their doctors must choose among several different drug combinations. Finding a combination that extends the time before the cancer worsens again is a major goal of treatment. The DREAMM-7 trial tested whether a newer three-drug combination could outperform an established standard combination. The newer combination included belantamab mafodotin, a drug that delivers a toxic payload specifically to myeloma cells. The standard combination included daratumumab, a well-established targeted therapy for myeloma. This correspondence in the New England Journal of Medicine presents both the original trial results and a scientific discussion about how to interpret them. The discussion focuses particularly on eye-related side effects and whether the reported discontinuation rates tell the full story. ## The DREAMM-7 Trial: How the Study Was Conducted The DREAMM-7 trial enrolled patients with multiple myeloma that had progressed after at least one line of previous therapy. The trial compared two treatment regimens: - **BVd:** belantamab mafodotin plus bortezomib plus dexamethasone - **DVd:** daratumumab plus bortezomib plus dexamethasone Bortezomib is a proteasome inhibitor, a type of drug that interferes with cancer cell growth. Dexamethasone is a steroid that helps fight myeloma and reduces inflammation. The trial measured progression-free survival, which is the time from treatment start until the cancer worsens or the patient dies. The trial authors reported that patients who received BVd had longer progression-free survival than patients who received DVd. This was the main positive finding of the study. However, the trial also documented a high rate of eye-related side effects in the BVd group. These side effects required careful monitoring and, in many cases, changes to the treatment schedule. ## Key Findings: Benefits and Risks The DREAMM-7 trial produced two headline results. First, the BVd combination extended progression-free survival compared with the DVd combination. Second, eye-related side effects were very common in the BVd group. The specific numbers reported were as follows: - **79%** of patients in the BVd group had ocular (eye) adverse events. - **84%** of patients had keratopathy (damage to the cornea, the clear front surface of the eye) or visual-acuity events (changes in how clearly the patient could see). - A majority of these eye events were **grade 3 or higher**, meaning they were serious and required medical attention. - **9%** of patients permanently discontinued belantamab mafodotin because of eye-related toxic effects. - The median duration until the first eye event occurred was **106 days**. - **78%** of patients were recorded as having a delayed treatment at the time of the analysis. These numbers show that eye problems were not rare events. They affected the large majority of patients treated with BVd. The question raised by the letter writers was whether the 9% discontinuation rate accurately reflects the long-term burden of these side effects. ## Understanding the Eye Side Effects Belantamab mafodotin can cause a distinctive pattern of eye toxicity. The main problems are keratopathy and changes in visual acuity. Keratopathy means damage to the cornea, the clear outer layer at the front of the eye. Visual-acuity events refer to changes in how well a person can see. These eye effects are graded by severity. Grade 3 or higher events are the most serious categories. In the DREAMM-7 trial, a majority of the eye events in the BVd group fell into this serious range. According to a separate publication cited in the correspondence, eye events of grade 2 or higher that are associated with belantamab mafodotin require treatment delays until the event resolves. This means that doctors must pause the drug and wait for the eye to improve before restarting treatment. The median time to the first eye event was 106 days. This means that, on average, patients experienced their first eye problem about three and a half months after starting treatment. This timing is important because it means eye monitoring must continue well beyond the first few weeks of therapy. ## The Scientific Debate: Concerns About the Data In a letter to the editor, Dr. Marko Lucijanic, Dr. Anica Sabljic, and Dr. Ivan Krecak raised concerns about how the eye-related discontinuation data were reported. Their main argument was that the median follow-up time in the trial was shorter than the median progression-free survival. This means the data set was still immature, or incomplete, at the time of analysis. The letter writers pointed out that 78% of patients were recorded as having a delayed treatment at the time of the analysis. They suggested that with longer follow-up, a considerable number of these patients might ultimately discontinue treatment permanently. In other words, the 9% discontinuation rate might rise over time. The letter writers also asked the trial authors to provide additional data. Specifically, they wanted to know: 1. How many patients with eye toxic effects attempted to restart the drug (a drug rechallenge)? 1. How many of those patients had a recurrence of eye problems? 1. How many ultimately discontinued treatment? These questions matter because they help patients and doctors understand the real-world experience of managing belantamab mafodotin eye toxicity. A temporary delay is very different from permanent discontinuation, both for the patient's quality of life and for the effectiveness of cancer treatment. ## The Authors' Response: How Eye Events Were Managed The trial authors, led by Dr. Vania Hungria and Dr. María-Victoria Mateos, responded directly to these concerns. They explained that dose delays were the primary strategy used to manage eye events in the DREAMM-7 trial. The authors defined these delays precisely. A dose delay meant holding the dose until the eye event improved to grade 1 or less on the Keratopathy and Visual Acuity (KVA) scale. The KVA scale is a standardized tool for grading eye toxicity. Once the eye event improved to grade 1 or less, the drug was restarted. For patients who had a KVA event of grade 3 or higher, the drug was restarted at a reduced dose. The dose was lowered from 2.5 milligrams per kilogram of body weight to 1.9 milligrams per kilogram. This dose reduction strategy allows patients to continue receiving the anti-cancer benefit of belantamab mafodotin while reducing the risk of further eye damage. The authors emphasized an important distinction: a dose delay is not the same as permanent discontinuation. This distinction is central to interpreting the trial results correctly. The authors provided specific follow-up data to support their position. Of the 209 patients who had at least one ocular event of grade 2 or higher on the KVA scale: - **190 patients (91%)** continued to receive belantamab mafodotin after the initial eye event. - These patients went on to receive a median of **8 additional treatment cycles**. - The range of additional cycles was **1 to 52**. These numbers show that the vast majority of patients who experienced a significant eye event were able to continue treatment. The authors also reiterated that a total of 9% of patients permanently discontinued belantamab mafodotin because of eye events, as stated in the original article. The authors also noted that since publication of the article, they report no further potential conflict of interest. ## Clinical Implications for Patients This exchange of letters highlights several important points for patients with multiple myeloma and their care teams. First, the BVd combination offers a progression-free survival benefit compared with the DVd combination. This means patients who receive BVd may live longer before their cancer worsens. This is a meaningful benefit for a disease that has progressed after prior therapy. Second, eye-related side effects are very common with BVd. Nearly 8 in 10 patients (79%) experienced ocular adverse events, and more than 8 in 10 (84%) had keratopathy or visual-acuity events. A majority of these events were grade 3 or higher. Patients considering BVd should be prepared for the possibility of significant eye problems. Third, most eye events can be managed with dose delays and dose reductions rather than permanent discontinuation. In the trial, 91% of patients with a grade 2 or higher eye event continued treatment after the event. These patients received a median of 8 additional cycles. This suggests that with careful monitoring and management, most patients can stay on treatment. Fourth, the timing of eye events matters. The median time to first eye event was 106 days. This means eye monitoring is essential throughout treatment, not just at the beginning. ## Limitations of the Study The letter writers raised a valid concern about the maturity of the data. The median follow-up time was shorter than the median progression-free survival. This means that many patients had not been followed long enough to know their final treatment outcome. Because of this, the 9% permanent discontinuation rate may not reflect the full picture. Some patients who were recorded as having a delayed treatment at the time of analysis (78%) might eventually discontinue treatment permanently. Longer follow-up will be needed to answer this question definitively. The letter writers also noted that the trial authors did not initially report how many patients attempted a drug rechallenge. The trial authors did not initially report how many patients had recurrent eye events. The trial authors did not initially report how many patients ultimately discontinued. The authors' response provided some of this information, showing that 190 of 209 patients (91%) continued treatment after their first significant eye event. However, the correspondence does not provide a full breakdown of rechallenge attempts, recurrences, and subsequent discontinuations over the entire follow-up period. Another limitation is that the correspondence format does not allow for the same level of detail as a full research article. The original DREAMM-7 publication contains the complete trial data, and readers seeking more comprehensive information should consult that article. ## Recommendations for Patients and Caregivers Based on this research and the scientific discussion it generated, patients with multiple myeloma who are considering belantamab mafodotin combination therapy should keep the following points in mind: 1. **Discuss the benefits and risks with your oncologist.** The BVd combination extended progression-free survival in the DREAMM-7 trial, but it also caused eye side effects in the large majority of patients. 1. **Plan for regular eye monitoring.** Eye events occurred at a median of 106 days after starting treatment. Monitoring should continue throughout therapy, not just in the first weeks. 1. **Report any changes in vision promptly.** Keratopathy and visual-acuity changes are the main eye concerns. Early reporting allows your care team to adjust treatment before the problem worsens. 1. **Understand that dose delays are common and are not the same as stopping treatment.** In the trial, 91% of patients with a significant eye event continued treatment after the event, receiving a median of 8 additional cycles. 1. **Ask about dose reduction strategies.** For grade 3 or higher eye events, the trial protocol reduced the belantamab mafodotin dose from 2.5 milligrams per kilogram to 1.9 milligrams per kilogram. This approach allowed patients to continue treatment. 1. **Ask your care team about the KVA scale.** This is the standardized tool used to grade eye toxicity and guide treatment decisions. 1. **Be aware that longer-term data are still emerging.** The median follow-up in the trial was shorter than the median progression-free survival, so the final discontinuation rate may change as more data become available. Patients should also feel empowered to ask their care team about the specific experience of their treatment center with belantamab mafodotin. Real-world experience can complement the information from clinical trials. ## Frequently Asked Questions ### What is the BVd combination and who was it tested in? BVd is belantamab mafodotin plus bortezomib plus dexamethasone. In the DREAMM-7 trial, it was tested in patients with multiple myeloma that had worsened after at least one prior treatment. It was compared with a standard combination called DVd, which is daratumumab plus bortezomib plus dexamethasone. ### Did BVd help patients live longer without their disease getting worse? Yes. In the DREAMM-7 trial, patients who received BVd had longer progression-free survival than those who received DVd. Progression-free survival is the time from starting treatment until the cancer worsens or the patient dies. This was the main positive finding of the study. ### How common were eye side effects with BVd? Eye side effects were very common. In the BVd group, 79% of patients had ocular adverse events, and 84% had keratopathy (damage to the clear front surface of the eye) or changes in visual acuity. A majority of these eye events were grade 3 or higher, meaning they were serious. ### What does it mean if an eye side effect is grade 3 or higher? Grade 3 or higher means the eye event was serious and required medical attention. In the DREAMM-7 trial, a majority of the eye events in the BVd group fell into this serious range. These events were managed mainly with temporary dose delays, not permanent discontinuation of treatment. ### If I have a serious eye side effect, will I have to stop treatment? Not necessarily. In the DREAMM-7 trial, 91% of patients who had a significant eye event were able to continue belantamab mafodotin after the event. They received a median of 8 additional treatment cycles. Dose delays and dose reductions were the main strategies used to manage eye problems. ### When do eye side effects usually start? In the DREAMM-7 trial, the median time to the first eye event was 106 days, or about three and a half months after starting treatment. This means eye monitoring must continue well beyond the first few weeks of therapy, throughout the treatment period. ### What did the letter writers question about the discontinuation rate? The letter writers noted that the median follow-up time was shorter than the median progression-free survival, so the data were still incomplete. They pointed out that 78% of patients had a delayed treatment at the time of analysis and suggested the 9% permanent discontinuation rate might rise with longer follow-up. ### If I have multiple myeloma that worsened after prior treatment and I'm offered belantamab mafodotin plus bortezomib and dexamethasone, when should I seek a second opinion? Seek a second opinion before starting belantamab mafodotin, bortezomib, and dexamethasone (BVd), because the choice between BVd and daratumumab, bortezomib, and dexamethasone involves a real trade-off: BVd extended progression-free survival, but 79% of patients had eye adverse events and 84% had keratopathy or visual-acuity events, mostly grade 3 or higher. An independent review can help weigh that benefit against eye monitoring, dose delays, and dose reductions. Diagnostic Detectives Network provides independent expert second opinions. ## Source Information **Original article title:** Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma **Original trial:** DREAMM-7 trial, published in the New England Journal of Medicine, August 1, 2024 (volume 391, pages 393-407). Authors: Hungria V, Robak P, Hus M, et al. **Correspondence:** Letters to the editor and authors' reply published in the New England Journal of Medicine, October 10, 2024 (volume 391, issue 14, pages 1364-1365). **Letter writers:** Marko Lucijanic, M.D., Ph.D., Anica Sabljic, M.D., and Ivan Krecak, M.D., Ph.D. (Dubrava University Hospital, Zagreb, Croatia; University of Rijeka Faculty of Medicine, Rijeka, Croatia). **Authors' reply:** Vania Hungria, M.D., Ph.D. (Clinica São Germano, São Paulo, Brazil) and María-Victoria Mateos, M.D., Ph.D. (Hospital Universitario de Salamanca, Salamanca, Spain). **Additional cited reference:** Lu R, Morphey A, Diaz F, Chen J, Razmandi A, Richards T. Management of ocular toxicity in patients receiving belantamab mafodotin. J Adv Pract Oncol 2023; 14: 300-6. *This patient-friendly article is based on peer-reviewed research.* --- Publisher: Diagnostic Detectives Network (https://diagnosticdetectives.com) — independent multi-expert medical second opinions, worldwide, private-pay. Author byline: Anton Titov, MD, PhD. Contact: https://diagnosticdetectives.com/pages/contact Canonical page: https://diagnosticdetectives.com/products/belantamab-mafodotin-combination-therapy-for-multiple-myeloma-benefits-eye-side-effects-and-what-patients-should-know