The combination of high doses of antimetabolites, R-HDS, and ASCT is feasible and effective in patients age 18 to 70 years old with secondary CNS lymphoma, and we propose it as a new standard therapeutic option.

SummaryThe most effective strategy to prevent central nervous system (CNS) dissemination in diffuse large B-cell lymphoma (DLBCL) remains an important, unmet clinical need. Herein, we report a retrospective analysis of risk-tailored CNS prophylaxis in 200 human immunodeficiency virus-negative adults with DLBCL treated with rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or similar. High risk of CNS relapse was defined by involvement of specific extranodal organs, or simultaneous presence of advanced stage and high serum lactate dehydrogenase level; CNS prophylaxis with high-dose methotrexate AE intrathecal chemotherapy (IT) was routinely used in high-risk patients diagnosed after 2007. CNS relapse risk was low in 93 patients and high in 107; 40 high-risk patients received prophylaxis, which consisted of IT alone in 7. At a median followup of 60 months, one low-risk and nine high-risk patients (1% vs. 8%; P = 0Á01) experienced CNS relapse. In the high-risk group, CNS relapses occurred in 8/67 (12%) patients who did not receive prophylaxis and in 1/40 (2Á5%) patients who did; the latter occurred in a patient managed with IT alone. CNS relapse rate was 12% (9/74) for patients treated with "inadequate" prophylaxis (none or IT only) and 0% (0/33) for patients managed with intravenous prophylaxis (P = 0Á03). In conclusion, high-dose methotrexate-based prophylaxis significantly reduces CNS failures in high-risk patients stratified by involvement of specific extranodal sites and International Prognostic Index.

HD-K is a safe and active salvage treatment in EMZL patients. This macrolide deserves to be further investigated in EMZL and other lymphoma categories.

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Purpose: NGR-hTNF exploits the tumor-homing peptide asparagine-glycine-arginine (NGR) for selectively targeting TNF-a to an aminopeptidase N overexpressed on cancer endothelial cells. Preclinical synergism with cisplatin was displayed even at low doses. This study primarily aimed to explore the safety of low-dose NGR-hTNF combined with cisplatin in resistant/refractory malignancies. Secondary aims included pharmacokinetics (PKs), pharmacodynamics, and activity.Experimental Design: NGR-hTNF was escalated using a doubling-dose scheme (0.2-0.4-0.8-1.6 mg/m 2 ) in combination with fixed-dose of cisplatin (80 mg/m 2 ), both given intravenously once every three weeks. PKs and circulating TNF-receptors (sTNF-Rs) were assessed over the first three cycles.Results: Globally, 22 patients (12 pretreated with platinum) received a range of one to ten cycles. Consistently with the low-dose range tested, maximum-tolerated dose was not reached. No dose-limiting toxicities (DLTs) were observed at 0.2 (n ¼ 4) and 0.4 mg/m 2 (n ¼ 3). One DLT (grade 3 infusion-related reaction) was observed at 0.8 mg/m 2 . This dose cohort was expanded to six patients without further DLTs.No DLTs were noted also at 1.6 mg/m 2 (n ¼ 3). NGR-hTNF exposure increased dose-proportionally without apparent PK interactions with cisplatin. No shedding of sTNF-Rs was detected up to 0.8 mg/m 2 . At the dose level of 0.8 mg/m 2 , expanded to 12 patients for activity assessment, a platinum-pretreated lung cancer patient achieved a partial response lasting more than six months and five patients maintained stable disease for a median time of 5.9 months.Conclusions: The combination of NGR-hTNF 0.8 mg/m 2 with cisplatin 80 mg/m 2 showed favorable toxicity profile and promising antitumor activity.