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Characterization of response and corneal events with extended follow-up after belantamab mafodotin (GSK2857916) monotherapy for patients with relapsed multiple myeloma: a case series from the first-time-in-human clinical trial

Multiple myeloma (MM) remains an incurable haematological malignancy typically characterised by multiple relapses requiring ongoing sequential therapy. This treatment paradigm is being challenged by novel immunotherapies that may be able to induce deeper and more durable responses than conventional treatments. Belantamab Mafodotin (belamaf, GSK2857916) is a humanized, afucosylated monoclonal anti-BCMA antibody conjugated to monomethyl auristatin-F (MMAF, a microtubule-disrupting agent) which demonstrated an overall response rate of 60% and a median progression-free survival (PFS) of 12.0 months (95% CI: 3.1–not reached [NR]) in a first-in-human clinical trial in relapsed MM (BMA117159; NCT02064387). In this study a maximum of 16 doses could be given, three weeks apart. The most significant events leading to dose reductions were blurred vision (12 of 35; 34%) and thrombocytopenia (6 of 35; 17%), with corneal events reported in 24 (69%) patients. All patients received prophylactic steroid eye drops four-times a day for four days commencing 24 hours pre-belamaf and fluorescein sodium 2% dye staining was performed at slit lamp examination. Within the context of the trial, greater characterisation of disease response and corneal events, including their management, is not available. We therefore report our experience following a median of 32.6 months followup of the five patients treated at our center with the recommended dose of 3.4 mg/kg Q3W. Baseline demographics and corneal events are shown in the Online Supplementary Table S1, efficacy parameters are summarised in Table 1. Case 1. This 51-year old female with 1q amplification and t(11;14) had received four prior lines and was proteasome inhibitor (PI) and immunomodulatory agent (IMiD) refractory. She was a contact lens wearer and initially continued this against medical advice. Her baseline eye examination was normal. She completed 16 doses of belamaf monotherapy and achieved a complete response (CR) with a PFS of 18.9 months, a treatment-free-interval (TFI) of 6.5 months before clinical relapse. Following dose three, she developed grade (G) III corneal events (dry eyes, photophobia) limiting her driving ability. This was managed by an increased frequency (2 hourly) and duration of dexamethasone eye drops and preservative-free (PF) lubricant eye drops until improvement to GI whereupon they were tapered slowly. Dosing was delayed by 98 days and recommenced with a 50% dose reduction (at 1.7 mg/kg). Further intermittent treatment delays were required due to GII corneal events, managed as previously with no further dose reductions. Corneal events fully resolved 9.5 months following the last dose of belamaf. Secondary cataracts were identified and surgically extracted. Case 2. This 51-year old male had four prior lines of therapy and was IMiD and daratumumab refractory. He had a history of laser ocular surgery and had a normal baseline eye examination. He completed 16 doses of belamaf monotherapy, achieving stringent CR (sCR) with resolution of extramedullary disease. This response was maintained after 34.4 months follow-up with a TFI of 20.0 months. Following two doses of belamaf he developed GIII corneal events (blurring of vision, dry eye) requiring increased frequency of dexamethasone eye drops (4 hourly), PF lubricant eye drops and interruption of belamaf dosing. Dose 3 was delayed by 50 days and reduced by 25% (2.55 mg/kg). Corneal events subsequently remained at <GII. He developed raised intra-ocular pressure, which responded to a topical pressure lowering agent and tapering of steroid eye drops. A further 25% dose reduction from original dose (1.7 mg/kg) was required due to asymptomatic GIII gamma-glutamyl transferase (GGT) elevation. Corneal events fully resolved 6.8 months following the last dose. Secondary cataracts were identified and surgically extracted. Case 3. This 57-year old female with 1q amplification and t(11;14) translocation received six prior lines, was IMiD refractory and had multiple co-morbidities (Arnold Chiari malformation with cerebellar tonsillar descent, pharyngeal dysphagia, diabetes and bronchiectasis) with poor tolerance to prior therapies. She had a history of dry eyes