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Abstract Background Despite recent advances, optimal therapeutic approaches applicable to subpopulations with primary central nervous system (CNS) lymphoma outside of clinical trials remain to be determined. Methods We performed a retrospective study of immunocompetent, adult patients with histologically confirmed diffuse large B‐cell lymphoma of the CNS (PCNSL). 190/204 (93%) patients (median age: 65) received one of five high‐dose methotrexate (HD‐MTX) containing chemotherapy regimens: MPV/Ara‐C (HD‐MTX, procarbazine, and vincristine, followed by cytarabine [Ara‐C]) (n = 94, 50%), MATRix (HD‐MTX, Ara‐C, thiotepa, and rituximab) (n = 19, 10%), HD‐MTX/Ara‐C (n = 31, 16%), HD‐MTX monotherapy (n = 35, 18%) and MBVP (HD‐MTX, carmustine, teniposide, prednisolone) (n = 11, 6%). Results Cumulative median HD‐MTX and Ara‐C doses were 17 g/m2 (range: 1–64 g/m2) and 12 g/m2 (0–32 g/m2) respectively. Using 14 g/m2 as the reference dose, the median HD‐MTX relative dose intensity (HD‐MTX‐RDI) was 1.25 (0.27‐4.57) with 84% receiving > 0.75. The overall response rate (ORR) was 72% (complete response: 50%) after completing HD‐MTX. At a median follow‐up of 3.41 years (0.06–9.42), progression‐free survival (PFS) and overall survival (OS) were different between chemotherapy cohorts, with the best outcomes achieved in the MPV/Ara‐C cohort (2‐year PFS 74%, 2‐year OS 82%; p = 0.0001 and p = 0.0024 respectively). On multivariate analysis, MPV/Ara‐C administration and HD‐MTX‐RDI > 0.75 were associated with longer PFS and OS. Conclusion Sequential, response‐adapted approaches can improve outcomes, even in older patients who are ineligible for a high‐intensity concurrent chemotherapy approach and do not undergo traditional consolidative strategies.

Abstract Background In primary central nervous system lymphoma (PCNSL), venous thromboembolism (VTE) can cause significant morbidity and hinder chemotherapy delivery. Objectives To assess VTE incidence, timing and adequacy of inpatient and outpatient VTE prophylaxis in patients with PCNSL receiving chemoimmunotherapy with curative intent. Patients/Methods We reviewed patients diagnosed with PCNSL between 1997 and 2018 who received methotrexate, procarbazine, and vincristine ± Rituximab. Patient demographics, VTE prophylaxis and incidence, adverse events of anticoagulation, and survival outcomes were collected. Results Fifty‐one PCNSL patients were included (median 67 years [range, 32‐87], 30 males [59%]). Thirteen patients (25%, 95% confidence interval [CI], 14‐40) developed VTE at a median of 1.6 months from diagnosis (range, 0‐4). Patients with Khorana Risk Score ≥2 were more likely to have VTE than those with a KRS

High expression of Mcl-1 promotes tumorigenesis and resistance to anticancer therapies. Here they report a macrocyclic molecule with high selectivity and affinity for Mcl-1 that exhibits potent anti-tumor effects as single agent and in combination with bortezomib or venetoclax in preclinical models of multiple myeloma and acute myeloid leukemia.

The Eμ-Myc lymphoma mouse model has been invaluable in the study of this disease. Here, the authors use multiple sequencing strategies to analyse the tumours in these mice and find recurrent inactivating mutations in Bcor, suggesting that this gene has a negative role in Mycsignalling.