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Background: Everolimus, an mTOR inhibitor, is active in refractory lymphomas. However, toxicity with flat dosing limits its usage. Speculatively, pharmacokinetically-targeted dosing could improve tolerability. Therefore, we studied serum-trough dosing with rituximab as maintenance after high-dose cyclophosphamide (HDC) consolidation in lymphoma patients.Patients/methods: After HDC, everolimus was dosed to serum trough levels (goal 3-15 ng/mL), with quarterly rituximab infusions for 1 year while maintaining < grade II non-hematologic and < grade III hematologic toxicities. Adult patients in first PR/CR with: mantle cell, transformed, double-hit, or high risk chronic lymphocytic leukemia or in second PR for any relapsed B cell lymphoma were eligible. Prophylaxis was given for encapsulated organisms, HSV and PCP. Serum IgG levels were maintained > 500 mg/dL.Results: 49 patients, median age: 59.0 years enrolled; MCL (26), CLL (10), transformed lymphoma (7), and other histologies (6). During the life of the study, the most frequent everolimus dosing has been 2.5 mg daily or 2.5 mg every other day; at these doses, serum levels are within the therapeutic range and non-hematologic toxicity is rare. At a median follow-up of 27.1 months, three patients remain on active therapy. Two patients withdrew secondary to potentially-attributable adverse events including a bacterial pneumonia and a viral pneumonia; this low rate of discontinuation compares well to other long-term everolimus trials. While a 58 and 76% EFS at 30 months for the entire cohort and MCL cohort, respectively, compares similarly to previously published HDC/rituximab data, longer follow-up is required.Conclusions: Pharmacokinetically-targeted dosing appears to increase everolimus tolerability. This finding may be applicable to other patient populations. [ABSTRACT FROM AUTHOR]

Left ventricular assist device (LVAD) core pathology may provide definitive cardiomyopathy etiology and guide management. We present a case of progressive cardiomyopathy concerning for myocarditis in a patient with cutaneous T cell lymphoma (CTCL) undergoing LVAD implantation. A 63-year-old man presented with mildly reduced left ventricular ejection fraction (LVEF) and ventricular tachycardia (VT). He had an extensive history of Gulf War Syndrome, heavy metal exposure, chronic kidney disease, hypercalcemia and cutaneous T cell lymphoma, managed with ultraviolet light therapy and methotrexate. Cardiac magnetic resonance (CMR) imaging demonstrated anteroseptal and inferolateral wall delayed gadolinium enhancement (DGE). Coronary angiography showed no coronary artery disease. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed reduced lateral and inferior wall perfusion but no myocardial FDG uptake or evidence of systemic CTCL. Endomyocardial biopsy demonstrated mild hypertrophy and marked interstitial fibrosis, however no evidence of sarcoidosis or myocarditis. Over the next 2 years, his cardiomyopathy progressed (LVEF 15-20%, LVDd 7.2cm). Upon readmission for VT and heart failure (HF), repeat FDG-PET showed myocardial FDG uptake - perfusion mismatch pattern prompting oral prednisone initiation. Durable LVAD was implanted 5 days later given clinical progression. LVAD core pathology showed myocardial T cell infiltration with a clonal T cell gene rearrangement (Figure 1). Peripheral blood and PET markers remained otherwise negative for CTCL. After LVAD, his HF and VT stabilized, and he is undergoing treatment plan for systemic T cell lymphoproliferative disorder. We present a case of myocardial T cell lymphoproliferative disorder presenting as progressive cardiomyopathy and highlight the role of LVAD core pathology in diagnosis. [ABSTRACT FROM AUTHOR]