Osimertinib Did Not Respond to a Pulmonary Adenocarcinoma with Triple Mutations of Epidermal Growth Factor Receptor, G719S, T790M and S768I

Uncommon epidermal growth factor receptor (EGFR) gene mutations include G719S, T790M and S768I. T790M gatekeeper mutation is the most frequent mechanism of acquired drug resistance to first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs). Osimertinib is a specific EGFR-TKI to overcome T790M resistance mutation. However, owing to a new drug and a rare mutation type, it remains unknown whether osimertinib is effective for acquired S768I. Herein, we reported a 76 year-old woman with pulmonary adenocarcinoma, which had acquired EGFR mutations of S768I and T790M in addition to original G719S after long gefitinib treatment. These mutations were detected in biopsy specimen of liver metastases. During two months of osimertinib, multiple liver metastases progressively enlarged. This case suggested that acquired S768I mutation might be resistant to osimeritinib, despite of co-occurrence of T790M

Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis

Funder: Research Committee on Intractable Vasculitides; The Ministry of Health, Labour and Welfare of Japan.Objectives: Evaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial. Methods: Patients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m2) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months. Patients in this cohort achieving remission were subsequently randomised to receive one of two regimens to prevent relapse. Results: 188 patients were studied: 95/188 (51%) men, median age 59 years (range 19–89), prior disease duration 5.0 years (range 0.4–34.5). 149/188 (79%) had previously received cyclophosphamide and 67/188 (36%) rituximab. 119/188 (63%) of relapses had at least one major disease activity item, and 54/188 (29%) received the higher dose glucocorticoid regimen. 171/188 (90%) patients achieved remission by 4 months. Only six patients (3.2% of the study population) did not achieve disease control at month 4. Four patients died in the induction phase due to pneumonia (2), cerebrovascular accident (1), and active vasculitis (1). 41 severe adverse events occurred in 27 patients, including 13 severe infections. Conclusions: This large prospective cohort of patients with relapsing AAV treated with rituximab in conjunction with glucocorticoids demonstrated a high level of efficacy for the reinduction of remission in patients with AAV who have relapsed, with a similar safety profile to previous studies

Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis

Funder: Research Committee on Intractable Vasculitides; The Ministry of Health, Labour and Welfare of Japan.Objectives: Evaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial. Methods: Patients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m2) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months. Patients in this cohort achieving remission were subsequently randomised to receive one of two regimens to prevent relapse. Results: 188 patients were studied: 95/188 (51%) men, median age 59 years (range 19–89), prior disease duration 5.0 years (range 0.4–34.5). 149/188 (79%) had previously received cyclophosphamide and 67/188 (36%) rituximab. 119/188 (63%) of relapses had at least one major disease activity item, and 54/188 (29%) received the higher dose glucocorticoid regimen. 171/188 (90%) patients achieved remission by 4 months. Only six patients (3.2% of the study population) did not achieve disease control at month 4. Four patients died in the induction phase due to pneumonia (2), cerebrovascular accident (1), and active vasculitis (1). 41 severe adverse events occurred in 27 patients, including 13 severe infections. Conclusions: This large prospective cohort of patients with relapsing AAV treated with rituximab in conjunction with glucocorticoids demonstrated a high level of efficacy for the reinduction of remission in patients with AAV who have relapsed, with a similar safety profile to previous studies