Ibrutinib monotherapy for relapse or refractory primary CNS lymphoma and primary vitreoretinal lymphoma: Final analysis of the phase II 'proof-of-concept' iLOC study by the Lymphoma study association (LYSA) and the French oculo-cerebral lymphoma (LOC) network.

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal centre B-cell subtype, with unmet medical needs. This study aimed to evaluate the efficacy and toxicity of ibrutinib in DLBCL-PCNSL PATIENTS AND METHODS: This prospective, multicentre, phase II study involved patients with relapse or refractory(R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma. The treatment consisted of ibrutinib (560 mg/day) until disease progression or unacceptable toxicity occurred. The primary outcome was the disease control (DC) rate after two months of treatment (P0 < 10%; P1 > 30%). RESULTS: Fifty-two patients were recruited. Forty-four patients were evaluable for response. After 2 months of treatment, the DC was 70% in evaluable patients and 62% in the intent-to-treat analysis, including 10 complete responses (19%), 17 partial responses (33%) and 5 stable diseases (10%). With a median follow-up of 25.7 months (range, 0.7-30.5), the median progression-free and overall survivals were 4.8 months (95% confidence interval [CI]; 2.8-12.7) and 19.2 months (95% CI; 7.2-NR), respectively. Thirteen patients received ibrutinib for more than 12 months. Two patients experienced pulmonary aspergillosis with a favourable (n = 1) or fatal outcome (n = 1). Ibrutinib was detectable in the cerebrospinal fluid (CSF). The clinical response to ibrutinib seemed independent of the gene mutations in the BCR pathway. CONCLUSION: Ibrutinib showed clinical activity in the brain, the CSF and the intraocular compartment and was tolerated in R/R PCNSL. The addition of ibrutinib to standard methotrexate-base induction chemotherapy will be further evaluated in the first-line treatment. CLINICAL TRIAL NUMBER: NCT02542514.

[Influence of the instillation of two versus three eyedrops of cyclopentolate 0.5% on refraction of Caucasian nonstrabismic children]. / Influence de l'instillation de 2 ou 3 gouttes de cyclopentolate à 0,5% sur la réfraction de l'enfant caucasien non strabique.

INTRODUCTION: Children's refraction can usually be measured using cyclopentolate 0.5%. Instilling three drops is time-consuming and inconvenient to both the clinical staff and the child. To remedy this situation, we investigated the refractive results of instilling two drops of cyclopentolate 0.5% at a 10-min interval compared with three drops at a 5-min interval in a group of a Caucasian nonstrabismic children. The kinetics of refraction in this population was also assessed. PATIENTS AND METHODS: We conducted a randomized cross-over study on 36 children aged between 4 and 13 years from March 1st to August 1st, 2003 at the University of Tours School of Ophthalmology. In protocol I, two cyclopentolate eyedrops were instilled in both eyes at a 10-min interval. In protocol II, three eyedrops were instilled at a 5-min interval. The refractive results were evaluated in terms of sphere and cylinder strength and axis. We used an auto-kerato-refractometer every 15 min from the first instillation for both protocols until the 90th min. RESULTS: Before the first drop instillation, there was no significant influence on skiascopy results for both eyes (-0.30+/-0.20 D for the right eye; -0.37+/-0.24 D for the left eye). The strength and the axis of the cylinder were comparable and stable (-0.5+/-0.18 D for strength; 5 degrees +/-22 for the axis) for all protocols and subjects tested. Sphere variation reached +1+/-0.6 D between t0 and t30 min for both protocols and remained stable between t30 and t90 min (+0.01+/-0.2 D). CONCLUSION: Instilling two eyedrops of cyclopentolate 0.5% at a 10-min interval in Caucasian nonstrabismic children aged 4-13 years is as effective as instilling three eyedrops at a 5-min interval in terms of kinetics and depth of cycloplegia. In addition, skiascopy can be performed as early as 30 min after the first instillation and until the 90th minute with the same effectiveness. The stability of astigmatism should be underlined in this population. Since these refractive results cannot be extrapolated for strabismic and ametropic children, we recommend, especially for the latter, instilling three drops for the first exam and only two thereafter, depending on the results.