by
Asim V. Farooq;
Simona Degli Esposti;
Rakesh Popat;
Praneetha Thulasi;
Sagar Lonial;
Ajay Nooka;
Andrzej Jakubowiak;
Douglas Sborov;
Brian E. Zaugg;
Ashraf Z. Badros;
Bennie H. Jeng;
Natalie S. Callander;
Joanna Opalinska;
January Baron;
Trisha Piontek;
Julie Byrne;
Ira Gupta;
Kathryn Colby
Introduction: Patients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody–drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from other MMAF-containing ADCs. Methods: Corneal examination findings from patients in DREAMM-2 were reviewed, and the clinical descriptions and accompanying images (slit lamp microscopy and in vivo confocal microscopy [IVCM]) of representative events were selected. A literature review on corneal events reported with other ADCs was performed. Results: In most patients receiving single-agent belamaf (72%; 68/95), MECs were observed by slit lamp microscopy early in treatment (69% had their first event by dose 4). However, IVCM revealed hyperreflective material. Blurred vision (25%) and dry eye (15%) were commonly reported symptoms. Management of MECs included dose delays (47%)/reductions (25%), with few patients discontinuing due to MECs (1%). The first event resolved in most patients (grade ≥2 MECs and visual acuity[each 77%], blurred vision [67%], and dry eye [86%]), with no reports of permanent vision loss to date. A literature review confirmed that similar MECs were reported with other ADCs; however, event management strategies varied. The pathophysiology of MECs is unclear, though the ADC cytotoxic payload may contribute to on- or off-target effects on corneal epithelial cells. Conclusion: Single-agent belamaf represents a new treatment option for patients with RRMM. As with other ADCs, MECs were observed and additional research is warranted to determine their pathophysiology. A multidisciplinary approach, involving close collaboration between eye care professionals and hematologist/oncologists, is needed to determine appropriate diagnosis and management of these patients. Trial Registration: ClinicalTrials.gov Identifier, NCT03525678.
by
Asim V. Farooq;
Simona Degli Esposti;
Rakesh Popat;
Praneetha Thulasi;
Sagar Lonial;
Ajay Nooka;
Andrzej Jakubowiak;
Douglas Sborov;
Brian E. Zaugg;
Ashraf Z. Badros;
Bennie H. Jeng;
Natalie S. Callander;
Joanna Opalinska;
January Baron;
Trisha Piontek;
Julie Byrne;
Ira Gupta;
Kathryn Colby
The authors of the above mentioned article would like to highlight the following corrections, based upon recent changes to the FDA label and guidance on the use of belamaf. • Page 3: The second sentence under ‘‘Methods’’ should be ‘‘In brief, eligible patients with RRMM were randomized (1:1) to receive belamaf 2.5- or 3.4-mg/kg every 3 weeks by intravenous infusion over 30 min or longer on day 1 of each cycle.’’ • Page 5: Table 1, Grade 4, Recommended dose modification currently reads ‘‘Permanently discontinue treatment’’. This should be ‘‘Consider treatment discontinuation for a Grade 4 event. Based on a benefit:risk assessment, if continuing treatment with belamaf is being considered, treatment may be resumed at a reduced dose after the event has improved to Grade 1 or better event.’’ • Page 6: Table 2, BCVA change, event outcomes as of last follow-up reads ‘‘26/44 (48).’’ This should be ‘‘26/44 (59)’’. Subjective dry eye, first event outcomes reads ‘‘2/14 (31).’’ This should be ‘‘2/14 (14)’’. Blurred vision, event outcome as of last follow-up, not recovered reads ‘‘9/24 (37).’’ This should be ‘‘9/24 (38)’’. • Page 8, 2nd column, 1st paragraph reads ‘‘28% (25/95) of patients’’ this should read ‘‘28% (25/88) of patients’’. • Page 9, 2nd column, first paragraph reads ‘‘Cogan microscysts’’. This should be ‘‘microcysts’’. • Page 10: Fig. 4 legend, reads ‘‘In vivo confocal microscopic image from the same patient (d–f) demonstrating hyperreflective opacities within the corneal epithelium.’’ This should be ‘‘(c–f)’’. • Page 10, 2nd column, first paragraph, first sentence reads: ‘‘Following the first dose of belamaf 2.5 mg/kg, he presented on day 27 with MECs characterized as mild/patchy in the periphery/mid-periphery on slit lamp microscopy (Fig. 5a, b). IVCM of the involved areas revealed hyperreflective opacities (Fig. 5c).’’ This should read as ‘‘(Fig. 4a, b)’’ and ‘‘(Fig. 4c–f)’’, respectively. • Page 18: Under ‘‘Recommended Monitoring, Diagnosis, and Management Techniques’’ and ‘‘Diagnosis and Staging of MECs’’ the final sentence currently reads ‘‘The eye care professional should also determine if the decline in BCVA is related to belamaf-associated examination finding(s).’’ This should be ‘‘Determine the recommended dosage modification of belamaf based on the worst finding in the worst affected eye. Worst finding should be based on either a corneal examination finding or a change in visual acuity per the KVA scale.’’ • Page 18: Under ‘‘Recommended Monitoring, Diagnosis, and Management Techniques’’ and ‘‘Management’’ the sentence currently reads ‘‘Treatment should be permanently discontinued for a grade 4 event.’’ This should be ‘‘Consider treatment discontinuation for a grade 4 event. Based on a benefit: risk assessment, if continuing treatment with belamaf is being considered, treatment may be resumed at a reduced dose after the event has improved to grade 1 or better event.’’ The original article has been corrected.
Dry eye disease (DED) represents a heterogeneous group of conditions with tear film insufficiency and signs and/or symptoms of ocular surface irritation. The clinical manifestations of DED can be highly variable; hence the diagnosis is often based on a combination of symptoms, signs, and clinical tests, given that any one of these alone would miss a significant number of patients. Similarly, the treatment must often be tailored to each patient by targeting the specific mechanisms involved in his or her disease. The purpose of this review is to summarize recent advances that have allowed us to better recognize, categorize, and treat patients with DED. The most notable new diagnostic tests in DED are tear film osmolarity, inflammatory biomarkers, and meibomian gland imaging. Therapeutically, anti-inflammatory therapy, meibomian gland heating and expression, and scleral contact lenses are some of the latest options available for treating DED.
by
Sagar Lonial;
Ajay Nooka;
Praneetha Thulasi;
Ashraf Z. Badros;
Bennie H. Jeng;
Natalie S. Callander;
Heather A. Potter;
Douglas Sborov;
Brian E. Zaugg;
Rakesh Popat;
Simona Degli Esposti;
Julie Byrne;
Joanna Opalinska;
January Baron;
Trisha Piontek;
Ira Gupta;
Reza Dana;
Asim V. Farooq;
Kathryn Colby;
Andrzej Jakubowiak
Belantamab mafodotin (belamaf) demonstrated deep and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) in DREAMM-2 (NCT03525678). Corneal events, specifically keratopathy (including superficial punctate keratopathy and/or microcyst-like epithelial changes (MECs), eye examination findings with/without symptoms), were common, consistent with reports from other antibody–drug conjugates. Given the novel nature of corneal events in RRMM management, guidelines are required for their prompt identification and appropriate management. Eye examination findings from DREAMM-2 and insights from hematology/oncology investigators and ophthalmologists, including corneal specialists, were collated and used to develop corneal event management guidelines. The following recommendations were formulated: close collaboration among hematologist/oncologists and eye care professionals is needed, in part, to provide optimal care in relation to the belamaf benefit–risk profile. Patients receiving belamaf should undergo eye examinations before and during every treatment cycle and promptly upon worsening of symptoms. Severity of corneal events should be determined based on corneal examination findings and changes in best-corrected visual acuity. Treatment decisions, including dose modifications, should be based on the most severe finding present. These guidelines are recommended for the assessment and management of belamaf-associated ocular events to help mitigate ocular risk and enable patients to continue to experience a clinical benefit with belamaf.