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Background The second-generation ALK tyrosine kinase inhibitor (TKI) ALC has demonstrated efficacy and acceptable safety in ALK+ NSCLC pts who have progressed on CRZ. However, resistance to ALC eventually develops, with secondary resistance mutations detected in approximately 50% of pts and a median progression-free survival (PFS) Trial design The second-generation ALK tyrosine kinase inhibitor (TKI) ALC has demonstrated efficacy and acceptable safety in ALK+ NSCLC pts who have progressed on CRZ. However, resistance to ALC eventually develops, with secondary resistance mutations detected in approximately 50% of pts and a median progression-free survival (PFS) Table . 1586TiP Primary Endpoint Blinded independent review committee (BIRC)−assessed PFS per RECIST v1.1 Secondary Endpoints BIRC-assessed intracranial PFS Overall survival Investigator- and BIRC-assessed ORR, time to response, and duration of response (DOR) BIRC-assessed intracranial ORR and DOR Safety/tolerability Health-related quality of life Selected Exploratory Endpoints BIRC-assessed CNS efficacy per Response Assessment in Neuro-Oncology Brain Metastases criteria (intracranial ORR, DOR, and PFS) Molecular determinants of efficacy and safety with BRG and ALC Clinical trial identification NCT03596866. Editorial acknowledgement Peloton Advantage, LLC, an OPEN Health Company; funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Legal entity responsible for the study ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Funding ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Disclosure S. Popat: Research grant / Funding (institution): Boehringer Ingelheim, Epizyme, BMS, Clovis Oncology, Roche, Lilly, Takeda; Honoraria (self): Boehringer Ingelheim, AstraZeneca, Roche, Takeda, Chugai Pharma; Advisory / Consultancy: Boehringer Ingelheim, Roche, Novartis, Pfizer, AstraZeneca, BMS, MSD, Guardant Health, AbbVie; Travel / Accommodation / Expenses: Boehringer Ingelheim, BMS, Merck Sharp & Dohme. G. Liu: Research grant / Funding (institution): Takeda, AstraZeneca, Roche, Bayer, Boehringer Ingerheim; Honoraria (self): Roche, Takeda, AstraZeneca, Bristol-Myers Squibb, AbbVie, Pfizer, Merck,Novartis, EMD Serano, Bayer; Advisory / Consultancy: Roche, Novartis, Pfizer. S. Lu: Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Hutchison MediPharma, Simcere, Roche, JS InnoPharm; Speaker Bureau / Expert testimony: AstraZeneca, Roche; Research grant / Funding (self): AstraZeneca, Hutchison MediPharma. G. Song: Full / Part-time employment: Takeda. V. Samnotra: Full / Part-time employment: Takeda. J.C. Yang: Advisory / Consultancy: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono Pharmaceutical, Daiichi Sankyo, Takeda, AstraZeneca, Hansoh Pharmaceuticals.

Summary. Two male first cousins with mild haemophilia A had baseline factor VIII levels of 12–15% and experienced bleeding requiring coagulation factor infusion therapy with trauma and surgical procedures. Both the patients with haemophilia A also had electrocardiographically documented symptomatic paroxysmal atrial fibrillation (PAF) for several years that had become resistant to pharmacological suppression. Radiofrequency ablation was considered in both the cases but deferred considering refusal of consent by the patients to undergo the procedure. Remission of arrhythmias has been reported in patients with iron-overload syndromes. Body iron stores assessed by serum ferritin levels were elevated in both men but neither had the C282Y or H63D genes for haemochromatosis. Calibrated reduction of iron stores by serial phlebotomy, avoiding iron deficiency, was followed by remission of symptomatic PAF in both cases. Iron reduction may be an effective treatment for arrhythmias apart from the classic iron-overload syndromes and deserves further study particularly in patients with bleeding disorders who might be at risk for arrhythmias and other diseases of ageing.