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Background: B-cell maturation antigen (BCMA) is a tumour necrosis superfamily cell-surface receptor required for plasma cell survival. This study evaluated safety, tolerability and preliminary clinical activity of GSK2857916, a novel anti-BCMA antibody conjugated to microtubule-disrupting agent monomethyl auristatin-F, in patients with relapsed/refractory multiple myeloma (MM). Methods: This international, multicentre, open-label, first-in-human Phase 1 study comprised dose escalation (Part 1) and dose expansion (Part 2) phases. Adults with histologically or cytologically confirmed MM, Eastern Cooperative Oncology Group performance status 0/1, and progressive disease following stem cell transplant, alkylators, proteasome inhibitors and immunomodulators were recruited. In Part 1, patients received GSK2857916 (0 03–4 6 mg/kg) via 1-hour intravenous infusion. In Part 2, patients received the selected dose of GSK2857916 (3 4 mg/kg) every 3 weeks. Primary endpoints were maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). All patients who received ≥1 dose were included in this prespecified administrative interim analysis (cut-off: 26 June 2017), which was performed for internal purposes. The study is ongoing (NCT02064387). Findings: Between July 2014 and February 2017, 73 patients were treated (Part 1 n=38; Part 2 n=35). No MTD was identified in Part 1. Based on safety/clinical activity, 3 4 mg/kg was selected as RP2D. Corneal events were common (42/73; 58%); most (37/42) were Grade 1/2 and did not result in treatment discontinuation in Part 2. The other most common Grade 3/4 events were thrombocytopenia (25/73; 34%) and anaemia (11/73; 15%). There were 12 treatmentrelated serious adverse events and no treatment-related deaths. Overall response rate at 3 4 mg/kg in Part 2 was 60% (21/35; 95% confidence interval: 42 1%–76 1%). Interpretation: At the identified RP2D, GSK2857916 is well tolerated and data suggest it has good clinical activity in heavily pretreated patients, thereby indicating that this may be a promising candidate for the treatment of relapsed/refractory MM. Funding: GlaxoSmithKline plc

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 MMAFcontaining 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

SummaryBortezomib (formerly PS-341) has significant activity in patients with relapsed multiple myeloma (MM), its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin, thus providing the rationale for combination therapy with bortezomib, doxorubicin and dexamethasone (PAD). Patients with untreated MM received four 21-d cycles of PAD, comprising bortezomib 1AE3 mg/m 2 on days 1, 4, 8 and 11, along with dexamethasone 40 mg on days 1-4, 8-11 and 15-18 during cycle 1 and days 1-4 during cycles 2-4. During days 1-4, patients also received 0, 4AE5 or 9 mg/m 2 of doxorubicin at dose levels 1, 2, and 3 respectively. Following peripheral blood stem cell (PBSC) collection, patients received high-dose melphalan (MEL200) with PBSC transplantation (PBSCT). After PAD induction alone, 20 of 21 patients (95%) achieved at least a partial response (PR), including complete response (CR) in five patients (24%). Twenty of 21 had PBSC mobilized, and 18 of 20 received MEL200/PBSCT. In an intention-to-treat analysis, response rates were: CR 43%, near CR 14%, very good PR 24%, PR 14% and stable disease 5%. PAD was effective, did not prejudice subsequent PBSC collection, and should be further evaluated in prospective randomized trials.

Interim analyses of a phase I study with GSK2857916, an antibody–drug conjugate against B cell maturation antigen, have previously reported a 60% overall response and 7.9 months progression-free survival in relapsed/refractory multiple myeloma (MM). We provide updated safety and efficacy results of the BMA117159 trial following an additional 14 months' follow-up. This open-label, first-in-human, phase I study was conducted at nine centres in the USA, Canada and the UK, and included adults with MM and progressive disease after stem cell transplantation, alkylators, proteasome inhibitors, and immunomodulators. In part 1, the recommended dose of 3.4 mg/kg was identified; in part 2, patients received GSK2857916 3.4 mg/kg once every 3 weeks. Selected part 2 safety/tolerability and efficacy endpoints are reported. Twenty-one (60.0%; 95% confidence interval (CI) 42.1–76.1) of 35 patients achieved partial response or better, including two stringent complete responses and three complete responses. The median progression-free survival was 12 months and median duration of response was 14.3 months. Thrombocytopenia and corneal events were commonly reported; no new safety signals were identified. GSK2857916 was well tolerated and demonstrated a rapid, deep and durable response in heavily pre-treated patients with relapsed/refractory MM, consolidating the interim analyses conclusions that GSK2857916 is a promising treatment for these patients.

Real-world assessment of the clinical impact of symptomatic infection with severe acute respiratory syndrome coronavirus (COVID-19 disease) in patients with multiple myeloma receiving systemic anti-cancer therapy Dear Editor, Infection with the novel coronavirus SARS-CoV-2, resulting in an acute respiratory disease (COVID-19), is the cause of the current pneumonia pandemic, with a rapid rise in cases being reported in the European Union and UK. 1,2 The UK index case was identified on January 31, 2020 and, given the rapid spread and high mortality rate of COVID-19, it is imperative to define the impact on patients with co-existing medical conditions. 3 Multiple myeloma (MM), the second-most common haematological malignancy, is a cancer of the mature B-cell lineage, and is associated with both cellular and humoral immune dysfunction that renders patients susceptible to infections, especially of the respiratory tract. [4][5][6][7] This, coupled with a median age at presentation of 70 years in a population with frequent co-existing medical conditions, means the outcomes of MM patients infected with COVID-19 warrants particular attention. We conducted a fully-anonymised prospective clinical audit where only MM patients with documented symptomatic COVID-19, whether managed in the inpatient or outpatient setting, were reported. All patients were tested within the secondary care setting and were receiving systemic anti-cancer therapy (SACT).At the time of analysis (May 18, 2020), 75 completed proformas from MM patients who tested swab-positive for COVID-19 had been received (Table I). The median age of COVID-19-positive MM patients was 73 years (range, 47-88), with 27Á5% of patients >80 years of age. Where ethnicity details were available (n = 51), most (82%) were Caucasian, with 16% being Afro-Caribbean. 41% of patients were newly-diagnosed MM receiving frontline therapy (NDMM); 24% had relapsed from their frontline therapy and were now receiving second-line therapy (1 st REL); and 35% had relapsed and/or refractory disease (RRMM). The median absolute lymphocyte count at presentation with COVID-19 symptoms was 600 cells/ll (range, 0-2500), with 90% of patients demonstrating hypo-gammaglobulinaemia affecting at least 1 sub-class (IgG> IgM>IgA). The male/female ratio was 1Á5, but varied with age (<75 years ratio 2Á33 vs. >75 years ratio 0Á94) as a consequence of significant age difference between the groups (P = 0Á049).The median time from the UK Index case to COVID-19 symptoms was 54 days (range, 23-88). 20Á5% of patients did not have a temperature on presentation but did have a cough, and 16% reported GI symptoms, with 20Á5% of patients acquiring COVID-19 whilst an inpatient for other reasons. 75% had evidence of pulmonary infiltrates primarily detected by chest radiograph. All but three patients were admitted for clinical care. Systemic anticancer therapy (SACT) was stopped a median of 0Á5 days (range, 5-23) after the onset of COVID-19 symptoms. Only nine of 70 patients received critical care support, with five pati...