Contributions
Abstract: EP1026
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
The B-cell maturation antigen–targeting antibody–drug conjugate belantamab mafodotin (belamaf; GSK2857916) is approved for the treatment of patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM). Ocular symptoms (eg, dry eye, blurred vision, etc) and eye examination findings including keratopathy (superficial punctate keratopathy and/or microcyst-like epithelial changes) and changes in visual acuity are common with belamaf. These may be managed with dose modification (reduction and/or delay) or treatment discontinuation. Durable responses have been observed despite dose modifications. The safety profile of belamaf and longer-term management of ocular events need to be characterized more fully to optimize clinical care.
Aims
To characterize the safety profile of belamaf in patients treated for ≥12 months, in a post-hoc analysis of the 2.5 mg/kg Q3W arm of the open-label, Phase 2 DREAMM-2 study at 13-month follow-up.
Methods
Patients with RRMM who had ≥3 prior therapies and were refractory to an immunomodulatory agent and proteasome inhibitor and refractory and/or intolerant to an anti-CD38 monoclonal antibody received single-agent belamaf. Eye exams, including a corneal exam and assessment of best corrected visual acuity (BCVA) change, were conducted at baseline and prior to each dose. Dose modifications (delays/reductions) were made based on the most severe Keratopathy and Visual Acuity scale grading, which considers corneal exam findings and BCVA changes from baseline. Recovery was defined as Grade 1 exam findings/no exam findings, and ≤1-line decline in BCVA vs baseline. Patient-reported ocular symptoms were graded per CTCAE version 4.03.
Results
Of 97 patients randomized to the belamaf 2.5 mg/kg cohort, the clinical benefit rate (minimal response or better) was 36% at the 13-month cut-off. A total of 14 patients (15%) had received ≥12 months of treatment with 2.5 mg/kg Q3W belamaf at data cut-off. All 14 patients had experienced ≥1 ocular event (maximum grade of 2 [14%], 3 [79%], or 4 [7%]), and required ≥2 dose delays, with dose reduction (to 1.92 mg/kg) in 12 patients (86%). Dose delay or reduction permitted recovery of ocular events so that treatment could be restarted in all 14 patients. Patients underwent a mean of 3.6 dose delays over the ≥12 months of belamaf treatment (median: 3.5, range: 2–6). Median duration of dose delays was 41 days (range: 4–212). Ten patients (71%) required dose delays of >63 days. In general in this subset of 14 patients, long delays did not appear to negatively impact clinical response to belamaf: 12 (86%) had a clinical response (partial response or better; 11 [79%] for ≥6 months). In the subset of 14 patients analyzed here, all 14 had keratopathy. Ocular symptoms occurred in 13 patients (93%), most commonly blurred vision (57%), dry eye (36%), visual acuity reduced (21%), and photophobia (21%). No patients had permanent complete vision loss.
Conclusion
In this subset of patients receiving belamaf treatment for ≥12 months, dose modification was effective in managing ocular symptoms and decreasing findings at eye examination, and allowed patients the clinical benefit gained from continuing treatment with belamaf. The safety profile of belamaf will be further characterized in ongoing analyses and studies.
Funding: GlaxoSmithKline (Study 205678, NCT03525678). Drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.
Keyword(s): B-cell maturation antigen, Multiple myeloma, Safety
Abstract: EP1026
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
The B-cell maturation antigen–targeting antibody–drug conjugate belantamab mafodotin (belamaf; GSK2857916) is approved for the treatment of patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM). Ocular symptoms (eg, dry eye, blurred vision, etc) and eye examination findings including keratopathy (superficial punctate keratopathy and/or microcyst-like epithelial changes) and changes in visual acuity are common with belamaf. These may be managed with dose modification (reduction and/or delay) or treatment discontinuation. Durable responses have been observed despite dose modifications. The safety profile of belamaf and longer-term management of ocular events need to be characterized more fully to optimize clinical care.
Aims
To characterize the safety profile of belamaf in patients treated for ≥12 months, in a post-hoc analysis of the 2.5 mg/kg Q3W arm of the open-label, Phase 2 DREAMM-2 study at 13-month follow-up.
Methods
Patients with RRMM who had ≥3 prior therapies and were refractory to an immunomodulatory agent and proteasome inhibitor and refractory and/or intolerant to an anti-CD38 monoclonal antibody received single-agent belamaf. Eye exams, including a corneal exam and assessment of best corrected visual acuity (BCVA) change, were conducted at baseline and prior to each dose. Dose modifications (delays/reductions) were made based on the most severe Keratopathy and Visual Acuity scale grading, which considers corneal exam findings and BCVA changes from baseline. Recovery was defined as Grade 1 exam findings/no exam findings, and ≤1-line decline in BCVA vs baseline. Patient-reported ocular symptoms were graded per CTCAE version 4.03.
Results
Of 97 patients randomized to the belamaf 2.5 mg/kg cohort, the clinical benefit rate (minimal response or better) was 36% at the 13-month cut-off. A total of 14 patients (15%) had received ≥12 months of treatment with 2.5 mg/kg Q3W belamaf at data cut-off. All 14 patients had experienced ≥1 ocular event (maximum grade of 2 [14%], 3 [79%], or 4 [7%]), and required ≥2 dose delays, with dose reduction (to 1.92 mg/kg) in 12 patients (86%). Dose delay or reduction permitted recovery of ocular events so that treatment could be restarted in all 14 patients. Patients underwent a mean of 3.6 dose delays over the ≥12 months of belamaf treatment (median: 3.5, range: 2–6). Median duration of dose delays was 41 days (range: 4–212). Ten patients (71%) required dose delays of >63 days. In general in this subset of 14 patients, long delays did not appear to negatively impact clinical response to belamaf: 12 (86%) had a clinical response (partial response or better; 11 [79%] for ≥6 months). In the subset of 14 patients analyzed here, all 14 had keratopathy. Ocular symptoms occurred in 13 patients (93%), most commonly blurred vision (57%), dry eye (36%), visual acuity reduced (21%), and photophobia (21%). No patients had permanent complete vision loss.
Conclusion
In this subset of patients receiving belamaf treatment for ≥12 months, dose modification was effective in managing ocular symptoms and decreasing findings at eye examination, and allowed patients the clinical benefit gained from continuing treatment with belamaf. The safety profile of belamaf will be further characterized in ongoing analyses and studies.
Funding: GlaxoSmithKline (Study 205678, NCT03525678). Drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.
Keyword(s): B-cell maturation antigen, Multiple myeloma, Safety