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Introduction: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is usually fatal. Risk stratification of patients has historically been poorly defined, and CNS prophylaxis with high-dose methotrexate (HDMTX) can be associated with multiple toxicities. The CNS International Prognostic Index (IPI) defines three patient risk groups for CNS disease. The aims of this study were to evaluate the toxicity of HDMTX and describe outcomes in HDMTX and non-HDMTX patients according to the CNS-IPI.Methods: 205 patients diagnosed with DLBCL between 2004 and 2014, initially treated with RCHOP-like chemotherapy and considered for HDMTX CNS prophylaxis were identified by pharmacy records at two teaching hospitals. Patient records were retrospectively reviewed for HDMTX toxicity, CNS-IPI calculation and CNS relapse.Results: 28 patients with DLBCL were selected for two doses of HDMTX. Two of 28 patients received only one dose, and three had their second dose reduced due to renal impairment. 28% of patients experienced nephrotoxicity. 24 HDMTX and 122 non-HDMTX patients were evaluable for the CNS-IPI. No significant difference in the CNS-IPI distribution between the two groups was identified (p = 0.695). Five patients had CNS relapse, two who received HDMTX and three who did not. No significant difference in CNS relapse rate was identified between 24 HDMTX patients propensity-matched to 24 non-HDMTX patients.Conclusions: HDMTX was well-tolerated by patients. Application of the CNS-IPI identifies a different population of candidates for CNS prophylaxis compared to traditional criteria. [ABSTRACT FROM AUTHOR]

Summary: Elderly patients may be heterogeneous in their abilities to tolerate immunochemotherapy‐associated toxicities. We describe the morbidity of rituximab‐chemotherapy combinations among 205 newly‐diagnosed diffuse large B‐cell lymphoma (DLBCL) patients aged ≥60 years from 3 tertiary hospitals between 2009 and 2016, and explore the utility of retrospectively‐assigned baseline Comprehensive Geriatric Assessment (CGA) in predicting these toxicities. Seventy‐three percent (146/201) experienced grade ≥3 toxicities, 81% (163/201) needed admission, 52% (107/205) had ≥2 unplanned admissions, 82/201 (41%) required dose reductions (DR) subsequent to Cycle 1, 39/166 (23%) had chemotherapy delays and 26/198 (13%) ceased therapy early. CGA was associated with pre‐emptive baseline DR and perhaps because of this, did not predict grade ≥3 toxicities, ≥2 unplanned admissions or subsequent DR. Three‐year overall survival (OS) of CGA‐fit, CGA‐unfit and CGA‐frail patients was 82%, 60% and 53%, respectively. Three‐year progression‐free survival (PFS) of CGA‐fit, CGA‐unfit and CGA‐frail patients was 66%, 58% and 46%, respectively. OS of CGA‐fit patients was not statistically different from CGA‐unfit patients, but was superior to CGA‐frail patients (hazard ratio 2·892, 95% confidence interval 1·275–6·559, P = 0·011). PFS differences were not statistically significant. Baseline DR and early therapy cessation were associated with inferior OS and PFS independent of CGA. Prospective studies are needed to confirm if CGA‐adapted treatment strategies minimize morbidity and improves survival. [ABSTRACT FROM AUTHOR]

Abstract Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable outcomes. Despite the majority of patients being cured with combination chemoimmunotherapy, up to 30% eventually succumb to the disease. Until recently, baseline prognostic assessment has centred on the International Prognostic Index (IPI), although this index is yet to impact strongly on treatment choice. Molecular features such as cell of origin, MYC and BCL-2 genetic alterations and protein overexpression were identified over a decade ago, yet their prognostic value is still not fully elucidated. Adding complexity are the plethora of new clinical, biological and molecular prognostic markers described in the recent literature, most of which lack independent validation, likely act as surrogate markers for those already in common use and have yet to substantially impact on therapeutic decision making. This review comprehensively assesses the value of individual prognostic markers in the clinical setting and their potential to predict response to novel agents, and ways to optimise their use in future research. [ABSTRACT FROM AUTHOR]

This is the first report of the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) with Rituximab (GEM-PR) for diffuse large B-cell lymphoma (DLBCL). Thirty-nine patients with relapsed or refractory DLBCL in this study received GEM-P with (n = 24) or without Rituximab (n = 15) 64% patients had Stage III/IV disease. The overall response rate (ORR) was 59% (95% CI 42.1-74.4); 11/39 (28%) patients attained complete response. Patients received a median of two cycles (1-4) of treatment. For GEM-PR group, the ORR was 67% (95% CI 45-84%) compared to 47% (95% CI 21-73%) in GEM-P alone. one-year progression-free survival was 51% (95% CI 28-69%) in GEM-PR group compared to 27% (95% CI 8-49%) in GEM-P alone (P = 0.04). GEM-P is an effective second-line regimen in patients with relapsed or refractory DLBCL and the addition of Rituximab appears to further improve outcomes. [ABSTRACT FROM AUTHOR]