Rakesh Popat, BSc, MBBS, MRCP, FRCPath, PhD, consultant hematologist, University College Hospital, honorary associate professor, University College London, discusses investigational strategies to mitigate belantamab mafodotin-blmf (Blenrep)–related keratopathy in multiple myeloma.

Research is being generated regarding how to improve management strategies for belantamab mafodotin–related keratopathy in patients with relapsed/refractory multiple myeloma, Popat explains. Findings from the pharmacokinetic analysis of the phase 2 DREAMM-2 trial (NCT03525678) suggest that the severity of keratopathy correlates with trough levels of belantamab mafodotin. 

As such, clinical rationale exists to extend the infusion time of belantamab mafodotin to elicit a lower trough level. Moreover, some of the ongoing DREAMM trials and other investigator-initiated studies will be dosing belantamab mafodotin in 4-to-6-week cycles rather than 21-day cycles to minimize keratopathy among patients, Popat says.

Additionally, investigators are parsing out whether eye care specialists are needed to manage keratopathy in patients with multiple myeloma receiving belantamab mafodotin. Hematologists typically manage a wide range of treatment-related adverse effects (TRAEs), so once the field develops a better understanding of mitigating keratopathy, hematologists may be able to manage the TRAE without insight from ophthalmologists, Popat explains. In turn, patients could be spared an additional appointment to an eye care specialist, Popat concludes. 

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Rakesh Popat, BSc, MBBS, MRCP, FRCPath, PhD, discusses investigational strategies to mitigate belantamab mafodotin-blmf–related keratopathy in multiple myeloma.  



Dr. Popat on Investigational Strategies for Belantamab Mafodotin–Related Keratopathy in Multiple Myeloma 

Rakesh Popat, BSc, MBBS, MRCP, FRCPath, PhD, consultant hematologist, University College Hospital, honorary associate professor, University College London, discusses mitigating belantamab mafodotin-blmf (Blenrep)–related keratopathy in relapsed/refractory multiple myeloma.

Keratopathy is a common adverse effect observed in approximately 70% of patients with relapsed/refractory multiple myeloma treated with belantamab mafodotin, Popat explains. Although not all patients develop symptoms, signs of keratopathy may be noted by an eye care specialist. Patients who develop symptomatic keratopathy may experience blurred vision, dry eye, gritty eyes, and photophobia, Popat says.

Preservative-free eye drops should be given to all patients before and during treatment with belantamab mafodotin to mitigate the risk of keratopathy. Moreover, dosing of these eye drops should be increased to every 2 to 3 waking hours for symptomatic patients to provide relief, Popat concludes.

Rakesh Popat, BSc, MBBS, MRCP, FRCPath, PhD, discusses mitigating belantamab mafodotin-blmf–related keratopathy in relapsed/refractory multiple myeloma.  



Dr. Popat on Mitigating Belantamab Mafodotin–Related Keratopathy in Multiple Myeloma 

Rakesh Popat, BSc, MBBS, MRCP, FRCPath, PhD, consultant hematologist, University College Hospital, honorary associate professor, University College London, discusses the toxicities associated with belantamab mafodotin-blmf (Blenrep) in relapsed/refractory multiple myeloma. 

Weighing the risks and benefits of all therapies in oncology is an important step of the treatment-decision process, Popat says. Moreover, all treatment recommendations should be personalized to the individual patient.

Findings from the phase 2 DREAMM-2 trial (NCT03525678), which led to the August 2020 FDA approval of belantamab mafodotin, demonstrated clinical activity and a tolerable safety profile with the antibody-drug conjugate in patients with heavily pretreated relapsed/refractory multiple myeloma. Notably, most patients who required treatment discontinuations stopped treatment because of disease progression rather than adverse effects (AEs), Popat says. 

Regardless, making a patient aware of the potential toxicities associated with belantamab mafodotin, including thrombocytopenia and keratopathy, is critical, Popat explains. Moreover, explaining how these AEs could affect a patient’s quality of life, as well as the how the efficacy of the agent compares with that of standard of care therapies, is important, Popat concludes.

Rakesh Popat, BSc, MBBS, MRCP, FRCPath, PhD, discusses the toxicities associated with belantamab mafodotin-blmf in relapsed/refractory multiple myeloma.  



Dr. Popat on Weighing Belantamab Mafodotin–Related Toxicities in Multiple Myeloma 

Rakesh Popat, BSc, MBBS, MRCP, FRCPath, PhD, consultant hematologist, University College Hospital, honorary clinical senior lecturer, University College London Cancer Institute, North Thames Clinical Research Network Specialty Lead for Hematology, Cancer Division, discusses unmet needs in triple-class refractory multiple myeloma.

Despite significant advancements that have been made over the past decade, multiple myeloma remains an incurable hematologic malignancy, Popat says. Currently, a major challenge in myeloma involves developing novel treatments for patients with triple-class refractory disease, Popat explains. 

These heavily pretreated patients have progressed on or become intolerant of proteasome inhibitors, immunomodulatory agents, and CD38-directed monoclonal antibodies, says Popat. 

These 3 drug classes have been brought into earlier lines of treatment in combination regimens for patients with multiple myeloma. Therefore, limited treatment options are available for patients with heavily pretreated progressive disease, concludes Popat. 

Rakesh Popat, BSc, MBBS, MRCP, FRCPath, PhD, discusses unmet needs in triple-class refractory multiple myeloma.  



Dr. Popat on Unmet Needs in Triple-Class Refractory Multiple Myeloma 

Rakesh Popat, BSc, MBBS, MRCP, FRCPath, PhD, consultant hematologist, University College Hospital, honorary clinical senior lecturer, University College London Cancer Institute, North Thames Clinical Research Network Specialty Lead for Hematology, Cancer Division, discusses results from the phase I, dose-expansion DREAMM-1 trial in relapsed/refractory multiple myeloma.

DREAMM-1 investigated the BCMA antibody-drug conjugate GSK2857916 for the first time in humans, explains Popat. Patients enrolled had progressive multiple myeloma after autologous stem cell transplant, or treatment with alkylators, proteasome inhibitors, and immunomodulatory agents.

In part 2 of the trial, heavily pretreated patients who were refractory to both an immunomodulatory agent and proteasome inhibitor had a nearly 60% overall response rate and median progression-free survival of 7.9 months was noted with the 3.4 mg/kg recommended dose of GSK2857916, which was identified in part 1 of the trial.

Thrombocytopenia and corneal adverse events including blurred vision, dry eye, and photophobia were commonly reported; however, the treatment was generally well-tolerated, concludes Popat. 

Rakesh Popat, BSc, MBBS, MRCP, FRCPath, PhD, discusses results from the phase I, dose-expansion DREAMM-1 trial in relapsed/refractory multiple myeloma.
 

Rakesh Popat, BSc, MBBS, MRCP, FRCPath, PhD

Articles

Dr. Popat on Investigational Strategies for Belantamab Mafodotin–Related Keratopathy in Multiple Myeloma

Dr. Popat on Mitigating Belantamab Mafodotin–Related Keratopathy in Multiple Myeloma

Dr. Popat on Weighing Belantamab Mafodotin–Related Toxicities in Multiple Myeloma

Dr. Popat on Unmet Needs in Triple-Class Refractory Multiple Myeloma

Dr. Popat on the DREAMM-1 Trial in Relapsed/Refractory Multiple Myeloma