In clinical trials, almost all patients treated with belantamab mafodotin experienced OAEs [17, 19]. As hematologists/oncologists may be unfamiliar with OAEs, clear guidance is needed to ensure appropriate care by healthcare teams. The expert panel discussed data and methodology from the DREAMM-7 and -8 trials as well as their own clinical experience and practical considerations for implementation in the real-world setting in Latin America. Four key themes were identified, under which pertinent clinical questions were defined to guide the recommendations.

Theme 1: Identifying Ocular Conditions at Baseline and OAEs in Response to Belantamab Mafodotin Treatment

A thorough assessment should be performed by an ophthalmologist prior to treatment start, as detailed in expert recommendations below. Where possible, further assessments are recommended during treatment, based on ocular signs and symptoms, and guided by the ophthalmologist (Fig. 1).

Fig. 1

Identifying ocular conditions at baseline and OAEs in response to belantamab mafodotin treatment. HCP, healthcare professional; OAE, ocular adverse event

Expert Recommendations

Q1: What is the ideal schedule for screening, identifying, and monitoring ocular events in patients treated with belantamab mafodotin?

Every patient must be examined by an ophthalmologist before starting treatment with belantamab mafodotin.

Additional assessment should be performed during treatment:

Where possible, prior to each dose/once a month for the first 3 months.

As appropriate based on signs and symptoms, which will be determined by an ophthalmologist.

Q3: How are belantamab mafodotin-associated ocular events classified?

Q4: Are there any patients who should be excluded from belantamab mafodotin treatment based on existing eye conditions?

No patient should be excluded based solely on existing eye conditions; treatment decisions should be made on an individual basis following comprehensive evaluation by the hematologist/oncologist and ophthalmologist, and with informed patient consent.

Patients with pre-existing eye conditions, such as Sjögren’s syndrome, corneal ulcer, severe dry eye, glaucoma, cataract, or prior refractive surgery, require a thorough benefit–risk assessment prior to starting belantamab mafodotin treatment.

Baseline Assessment and Monitoring of OAEs

Corneal epithelial changes, with or without symptoms, have previously been reported in patients treated with belantamab mafodotin; most ocular events were manageable and resolved quickly [23, 24]. In the DREAMM-7 and -8 clinical trials, 79% and 89% of patients, respectively, experienced any-grade OAEs. Common OAEs include eye pain, blurred vision, photophobia, eye irritation, and foreign-body sensation. Bilateral worsening of visual acuity (20/50 or worse) was seen in 34% of patients in both studies [17, 19].

Some existing ocular conditions, such as dry eye, may increase the risk of on-treatment OAEs; therefore, pre-treatment evaluation is important to assess ocular health at baseline and identify patients who may benefit from more regular assessment or supportive medications [23, 24]. Cataracts, which affect the lens of the eye, are not expected to be linked to belantamab mafodotin treatment; however, the panel agreed that all ocular conditions should be recorded at baseline to ensure accurate attribution of the cause of each condition and to enable monitoring of changes.

A post hoc analysis of the DREAMM-7 and -8 data showed that bilateral worsening of visual acuity and rates of OAEs were highest in the first 3 months of treatment [25, 26]; therefore, we recommend ocular assessment during this time period. Although recommendations are provided here for the ideal schedule for on-treatment ophthalmology assessments (Fig. 1), the panel acknowledged that in the real-world setting, access may be limited in some regions of Latin America. Where regular assessments are not possible, the treating physician should maintain high awareness for ocular symptoms, especially in the first 3 months of treatment.

Full assessment of ocular health should take into consideration both ocular signs, as assessed by the ophthalmologist, and symptoms, as assessed by the HCP/patient. In the clinical trials, ocular assessments were graded using the keratopathy visual acuity (KVA) scale, which considers both corneal exam findings and change in best corrected visual acuity [17, 19, 24]. Findings were graded as mild to severe and used to guide dose modification decisions (Table 1). The expert panel agreed that tools such as the KVA are not commonly used by ophthalmologists in the real-world setting. An objective, reproducible grading system is needed; however, this must be balanced with practicality and ease of use. Considering the need for more real-world, regional data for patients with RRMM, consistency in the recording of OAEs will also be important to ensure that data can be collected and published. Symptom-based questionnaires, such as the OSDI, may not be routinely used in clinical practice in Latin America, but are simple, reliable, and free to access [27].

The panel emphasized the importance of assessing the overall benefit–risk profile when interpreting baseline ophthalmologic findings. For example, in cases where cataract surgery is indicated, prompt initiation of myeloma treatment should be prioritized, and cataract surgery can be safely delayed until the patient is stable. In cases where existing ocular conditions may heighten the risk of adverse events, patients should be provided with all the information needed to make an informed decision about their treatment.

Theme 2: Belantamab Mafodotin Management and Dose Adjustment for Ocular Events

Dependent on severity, some OAEs may warrant modification of the belantamab mafodotin dose or schedule. Where possible, priority should be given to maintaining MM control, and additional medications may help to manage ocular symptoms (Fig. 2).

Fig. 2

Belantamab mafodotin management and dose adjustment for OAEs. MM, multiple myeloma; OAE, ocular adverse event

Expert Recommendations

Q5: What are the belantamab mafodotin dose/schedule modification protocols for managing ocular events?

Dose/schedule decisions should be discussed between the ophthalmologist and hematologist/oncologist, with priority given to effective MM control. If dose modification is considered necessary, the decision to reduce dose level and/or increase dosing interval should be made on a case-by-case basis.

As a general guide:

Mild: (minimum keratitis; no impact on visual acuity)—maintain treatment.

Moderate: (moderate keratitis; some impact on visual acuity)—reduce dose level and/or increase dosing interval.

Severe: (severe keratitis with pain; significant impact on visual acuity)—further reduce dose level and/or increase dosing interval; consider interruption of treatment.

Guidance used in the DREAMM-7 and -8 clinical trials may help inform selection of an alternate dose level/schedule (Table 1).

Q6: What additional management options are there for patients who experience ocular events?

Continuous use of lubricants (e.g., sodium hyaluronate) or gels (e.g., dexpanthenol 5%) throughout the treatment is recommended; preservative-free options are preferred where available.

The use of contact lenses should typically be avoided but may be necessary in some cases at the discretion of the ophthalmologist.

The use of topical antibiotics and topical corticosteroids may be beneficial but should be used at the discretion of the ophthalmologist.

Use of other medications, including non-prescription medications or prior prescriptions, should be discussed with treating physician.

Q7: Are there any ocular events that indicate permanent discontinuation of belantamab mafodotin treatment?

No ocular events indicate permanent discontinuation of belantamab mafodotin treatment.

Treatment decisions should be guided by the hematologist/oncologist, and ophthalmologist, and by informed patient decision.

Table 1 KVA grading and dose modification used in DREAMM-7 and -8 clinical trials [25, 26]Dose/Schedule Adjustments and Additional Management Options

In the DREAMM-7 and -8 clinical trials, OAEs were managed by dose modification or interruption and guided by KVA grading, as outlined in Table 1. In DREAMM-7 and -8, 44% and 59% of patients had dose reductions, 78% and 83% had dose delays/interruptions, respectively, and 9% discontinued treatment in each study as a result of any ocular event [17, 19]. For patients experiencing bilateral worsening of visual acuity (20/50 or worse), the median time to resolution of first event was 64 and 57 days, respectively, in DREAMM-7 and -8; 98% and 92% of first events had improved by the data cutoff [17, 19, 28].

The panel emphasized the importance of deep responses in the treatment of MM [29, 30]. Over the course of both studies, the median time between doses increased after the initial 3 months treatment, and this was associated with a decrease in occurrence of ocular events [25, 26]. Importantly, most patients had a partial response or better before their first dose delay; high response rates were maintained throughout treatment [18, 25, 26]. Those who underwent dose modifications were still able to derive clinical benefit, and median PFS was not impacted [25, 26].

DREAMM-9 is an ongoing study investigating different dosing schedules of belantamab mafodotin in combination with bortezomib, lenalidomide, and dexamethasone in patients with NDMM. Data are preliminary, but initial results (n = 10–19 per cohort) suggest that efficacy was maintained and incidence of OAEs was reduced with lower doses and longer dosing intervals [31].

The expert panel discussed the importance of balancing the risks associated with OAEs with those of MM. RRMM is a serious disease, and outcomes are especially poor in Latin America [2, 11, 12]. In contrast, most belantamab mafodotin-related OAEs are manageable and resolve quickly [17, 19, 25, 26]. In practice, each case should be discussed between the ophthalmologist and hematologist/oncologist to determine the best course of action, but general guidance is provided here (Fig. 2); grade 2 keratopathy was largely considered to be the threshold for dose modification [25, 26, 32]. Where possible, priority should be given to maintaining control of MM, and the hematologist/oncologist should advise whether dose modification is feasible without compromising efficacy. The guidance used in the DREAMM-7 and -8 clinical trials may help inform selection of an alternate dose level/schedule (Table 1). Patient perspectives should also be considered, and the patient should be provided with all the information needed to make an informed decision.

Prophylactic or reactive treatments may also help prevent or reduce ocular symptoms, and use of these should be guided by the ophthalmologist. In the DREAMM-7 and -8, all patients were advised to use preservative-free artificial tears throughout treatment [17, 19]; however, the panel noted that preservative-free options, though preferred, may not be available in all regions. Additionally, the availability of over-the-counter medications varies by country, highlighting the need for physicians to discuss the use of all medication options with patients. For example, eye drops for glaucoma may cause corneal damage, requiring closer management by the ophthalmologist when used in conjunction with belantamab mafodotin [33].

Theme 3: Multidisciplinary Collaboration for Effective Management of OAEs

A multidisciplinary team (MDT) is essential to provide optimal care for patients receiving belantamab mafodotin. Timely exchange of information and appropriate educational resources are key (Fig. 3).

Fig. 3

Multidisciplinary collaboration and patient-centric approaches for management of OAEs. HCP, healthcare professional; MM, multiple myeloma; OAE, ocular adverse event; QoL, quality of life

Expert Recommendations

Q8: What are the best practices for collaboration between hematologists/oncologists and ophthalmologists?

The wider MDT should also include nurses, social workers, psychologists, etc.; all members should be educated on the risks and management of OAEs.

Q9: What are the key clinical indicators that an ophthalmology referral is necessary?

Q10: What educational resources and strategies are needed to improve HCP understanding of the belantamab mafodotin ocular event profile?

Materials need to be clear, concise, and tailored to the audience (i.e., materials for ophthalmologists vs hematologists/oncologists).

Multidisciplinary Collaboration, Access Considerations, and Educational Needs

A multidisciplinary approach involving hematologists/oncologists, ophthalmologists, and the wider patient care team is essential for effective management of OAEs and belantamab mafodotin treatment decisions [24]. Some patients may also have regular contact with other support services who play a significant role in their care; these people should also be considered part of the wider MDT. Given the lack of overlap in expertise, educational resources and regular communication are of key importance for all members of the MDT.

The expert panel discussed that most hematologists/oncologists in Latin America may not have existing relationships with ophthalmologist(s); therefore, it is essential to establish contacts prior to treatment and to clearly define roles and responsibilities. They further acknowledged that in some regions, issues such as access from remote areas or insurance coverage may limit the ability of the patient to be seen by a preferred ophthalmologist. In such cases, clear educational materials are needed to ensure the treating ophthalmologist is well informed. Likewise, regular ophthalmology visits may not always be feasible, so hematologists/oncologists must be educated in recognizing anticipated OAEs and understanding when a referral is necessary. In particular, the panel emphasized the importance of reassuring HCPs that the majority of OAEs arising through belantamab mafodotin are manageable and resolve with dose adjustments. To date, no cases of permanent loss of vision have been reported [17, 19, 25, 26]. Furthermore, data suggest that ocular symptoms may not have a large impact on daily functioning and quality of life, discussed in more detail below [20, 34].

Theme 4: Patient-Centric Approaches for Management of OAEs

Patients should be well informed and understand the overall benefit–risk of belantamab mafodotin treatment. Regular assessment of symptoms is key to managing treatment decisions, with an overall goal of maintaining quality of life while keeping patients on treatment (Fig. 3).

Expert Recommendations

Q11: How can clinicians effectively communicate the benefits and risks of belantamab mafodotin to support informed decision-making?

Q12: What role do patient-reported outcomes play in the early detection and management of ocular events?

HCPs and patients should discuss ocular symptoms regularly; findings will help tailor care to maintain quality of life.

A questionnaire such as the OSDI tool may help HCPs and patients identify and monitor ocular symptoms.

Impact of Ocular Symptoms on Quality of Life and Patient Educational Needs

Severe ocular symptoms may be associated with fear of long-term damage to sight, and even mild symptoms could impact daily function and quality of life, for example, limiting independence or ability to drive [34, 35]. Ensuring that patients are fully educated about the anticipated ocular symptoms before starting treatment will help to manage concerns and enable them to plan for disruptions to their daily lives [24]. The panel agreed that physicians should reassure patients that OAEs are manageable and unlikely to result in long-term effects on vision [17, 19, 25, 26].

The BelaRD trial is an ongoing study of belantamab mafodotin, lenalidomide, and dexamethasone in patients with NDMM. During the study, the OSDI tool was used to assess the impact of ocular symptoms on vision-related functioning. Most patients reported limited impact on activities of daily living: around 60% of patients reported “some of the time” and 27–37% reported “none of the time”. Of note, there was not a strong correlation between ocular symptoms and activities of daily living, with symptoms being reported more frequently than impact on daily functioning [34]. Consistent with this, in the DREAMM-7 and -8 clinical trials, there was no clinically meaningful difference in patient-reported quality of life between belantamab mafodotin treatment groups compared with the comparator groups, and exploratory analysis indicated minor impact of blurred vision on quality of life [17, 19, 20].

Comprehensive understanding is key to enable patients to make informed decisions about their care and may also increase compliance with symptom reporting and preventative measures. During the DREAMM-7 and -8 studies, regular assessment of ocular symptoms helped to establish individualized dose schedules that enabled patients to stay on treatment and derive clinical benefit [25, 26].