Ibrutinib- and bortezomib-extended R-CHOP induction in elderly higher-risk patients newly diagnosed with diffuse large B-cell lymphoma - first analysis of toxicity and efficacy signals.

Diffuse large-cell B-cell lymphoma (DLBCL) is the most common lymphoid malignancy. About 30-40% of the patients will not be cured by standard Rituximab (R)-CHOP-like immune-chemotherapy, and many of them experience relapse and eventually succumb to their disease. Enhancing first-line efficacy in patients at higher risk, among them many elderly, is key to improve long-term outcomes. Numerous attempts to combine R-CHOP with targeted agents failed in large randomized phase III trials. The addition of Ibrutinib enhanced survival in younger patients, but increased toxicity across all age groups, especially in the elderly. Older DLBCL patients impose particular challenges, since they often present with more advanced disease, and exhibit treatment-relevant comorbidities. ImbruVeRCHOP trial aims at identifying patients who need that benefit from rationally augmented first-line regimens without experiencing overt toxicity and detecting their molecular signatures of response. This first analysis presents encouraging feasibility, safety, and preliminary response data in elderly high-risk DLBCL patients.

The spectrum of thyroid disorders in adult type 1 diabetes mellitus.

BACKGROUND: Thyroid disorders such as goiter, nodules, autoimmune thyroid disease and thyroid dysfunction have rarely been investigated in adult type 1 diabetes mellitus. Our aim was to study the spectrum of thyroid disorders in adult type 1 diabetic subjects and compare them with results obtained from a sample of the general adult population. METHODS: The study population comprised 224 type 1 diabetic and 3481 non-diabetic subjects aged 20-69 years. Thyroid function (TSH, FT3 and FT4) and serum autoantibodies to thyroperoxidase (anti-TPO-Ab) were evaluated from blood samples. Thyroid structure and size were measured by ultrasound. RESULTS: Type 1 diabetic subjects had a higher risk of known thyroid disease [odds ratio (OR) 1.78, 95% confidence interval (CI) 1.11-2.85], a lower risk of goiter (OR 0.73; 95%-CI 0.54-0.99) and nodules (OR 0.54; 95%-CI 0.35-0.85), and a higher risk of anti-TPO-Ab >200 IU/mL (OR 1.94; 95%-CI 1.28-2.95) compared to the reference population. Furthermore, diabetic subjects had lower serum FT3 levels than the non-diabetic references (adjusted mean 5.00 pmol/L; 95%-CI 4.88-5.12 pmol/L versus 5.27 pmol/L; 95%-CI 5.24-5.30 pmol/L). CONCLUSIONS: Adult type 1 diabetes mellitus is associated with a decreased risk of goiter and nodules and an increased risk of thyroid autoimmunity. A diabetes-related low T3 syndrome may contribute to the differences in thyroid function between type 1 diabetic and non-diabetic subjects.