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  Differences in Cytogenetic Abnormality and Clinical Presentation in Multiple Myeloma Between African Americans and European Americans

  Chan, Sin; Zou, Ying, M.D., Ph.D. (2016)

  Multiple myeloma (MM) is a hematologic cancer with a prominent racial disparity between African Americans and European Americans. African Americans are two-to-three times more likely to be diagnosed, but they have a better prognosis. Cytogenetic abnormalities are associated with prognosis and clinical presentations, which can provide insight into disease outcome, too. This study aimed to assess the basis of racial disparities observed in prevalence and prognosis by comparing racial differences in cytogenetic abnormalities and clinical presentations in MM patients. Conventional FISH and MACS FISH, a more sensitive assay in detection of cytogenetic abnormalities, were compared first. MACS FISH was able to detect a higher frequency of all cytogenetic abnormalities. The comparison of cytogenetic abnormalities and clinical presentations between the two races from MACS FISH supported the view that European Americans have a poorer prognosis than African Americans possibly to a higher frequency of high-risk cytogenetic abnormalities associated with more severe clinical presentations in European Americans.
• Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody–Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study

  Farooq, Asim V.; Degli Esposti, Simona; Popat, Rakesh; Thulasi, Praneetha; Lonial, Sagar; Nooka, Ajay K.; Jakubowiak, Andrzej; Sborov, Douglas; Zaugg, Brian E.; Badros, Ashraf Z.; et al. (Springer Science and Business Media LLC, 2020-07-25)

  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. © 2020, The Author(s).
• Correction to: Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody–Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study (Ophthalmology and Therapy, (2020), 10.1007/s40123-020-00280-8)

  Farooq, Asim V.; Degli Esposti, Simona; Popat, Rakesh; Thulasi, Praneetha; Lonial, Sagar; Nooka, Ajay K.; Jakubowiak, Andrzej; Sborov, Douglas; Zaugg, Brian E.; Badros, Ashraf Z.; et al. (Springer Nature, 2020-09-12)

  The authors of the above mentioned article would like to highlight the corrections in https://doi.org/10.1007/s40123-020-00289-z, based upon recent changes to the FDA label and guidance on the use of belamaf.