MGMT promoter hypermethylation appears to be a useful marker for predicting survival in patients with B-DLCL treated with multidrug regimens including cyclophosphamide.

Role of interim-PET (I-PET) in diffuse large

Key Points• 18FDG PET/CT is a very important staging tool for patients with PMBCL. • Metabolic activity defined by TLG on the baseline PET scan is a powerful predictor of PMBCL outcome.The International Extranodal Lymphoma Study Group (IELSG) 26 study was designed to evaluate the role of 18 F-fluorodeoxyglucose (18FDG) positron emission tomography/ computed tomography (PET/CT) in the management of primary mediastinal (thymic) large B-cell lymphoma (PMBCL). We examined the prognostic impact of functional PET parameters at diagnosis. Metabolic activity defined by the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) was measured on baseline 18FDG PET/CT following a standard protocol in a prospectively enrolled cohort of 103 PMBCL patients. All received combination chemoimmunotherapy with doxorubicin-and rituximab-based regimens; 93 had consolidation radiotherapy. Cutoff values were determined using the receiver-operating characteristic curve. At a median follow-up of 36 months, progression-free survival (PFS) and overall survival (OS) were 87% and 94%, respectively. In univariate analysis, elevated MTV and TLG were significantly associated with worse PFS and OS. Only TLG retained statistical significance for both OS (P 5 .001) and PFS (P < .001) in multivariate analysis. At 5 years, OS was 100% for patients with low TLG vs 80% for those with high TLG (P 5 .0001), whereas PFS was 99% vs 64%, respectively (P < .0001). TLG on baseline PET appeared to be a powerful predictor of PMBCL outcomes and warrants further validation as a biomarker. The IELSG 26 study was registered at www.clinicaltrials.gov as #NCT00944567. (Blood. 2015;126(8):950-956)

(90)Y-ibritumomab consolidation after achieving PR or CR/CRu to induction confers 3-year benefit in median PFS with durable 19% PFS advantage at 8 years and improves TTNT by 5.1 years for patients with advanced FL.

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Summary Background Secondary CNS lymphoma is a rare but potentially lethal event in patients with diffuse large B-cell lymphoma. We aimed to assess the activity and safety of an intensive, CNS-directed chemoimmunotherapy consolidated by autologous haematopoietic stem-cell transplantation (HSCT) in patients with secondary CNS lymphoma. Methods This international, single-arm, phase 2 trial was done in 24 hospitals in Italy, the UK, the Netherlands, and Switzerland. Adults (aged 18–70 years) with histologically diagnosed diffuse large B-cell lymphoma and CNS involvement at the time of primary diagnosis or at relapse and Eastern Cooperative Oncology Group Performance Status of 3 or less were enrolled and received three courses of MATRix (rituximab 375 mg/m 2 , intravenous infusion, day 0; methotrexate 3·5 g/m 2 , the first 0·5 g/m 2 in 15 min followed by 3 g/m 2 in a 3 h intravenous infusion, day 1; cytarabine 2 g/m 2 every 12 h, in 1 h intravenous infusions, days 2 and 3; thiotepa 30 mg/m 2 , 30 min intravenous infusion, day 4) followed by three courses of RICE (rituximab 375 mg/m 2 , day 1; etoposide 100 mg/m 2 per day in 500–1000 mL over a 60 min intravenous infusion, days 1, 2, and 3; ifosfamide 5 g/m 2 in 1000 mL in a 24 h intravenous infusion with mesna support, day 2; carboplatin area under the curve of 5 in 500 mL in a 1 h intravenous infusion, day 2) and carmustine–thiotepa and autologous HSCT (carmustine 400 mg/m 2 in 500 mL glucose 5% solution in a 1–2 h infusion, day −6; thiotepa 5 mg/kg in saline solution in a 2 h infusion every 12 h, days −5 and −4). The primary endpoint was progression-free survival at 1 year. Overall and complete response rates before autologous HSCT, duration of response, overall survival, and safety were the secondary endpoints. Analyses were in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov , NCT02329080 . The trial ended after accrual completion; the database lock was Dec 31, 2019. Findings Between March 30, 2015, and Aug 3, 2018, 79 patients were enrolled. 75 patients were assessable. 319 (71%) of the 450 planned courses were delivered. At 1 year from enrolment the primary endpoint was met, 42 patients were progression free (progression-free survival 58%; 95% CI 55–61). 49 patients (65%; 95% CI 54–76) had an objective response after MATRix–RICE, 29 (39%) of whom had a complete response. 37 patients who responded had autologous HSCT. At the end of the programme, 46 patients (61%; 95% CI 51–71) had an objective response, with a median duration of objective response of 26 months (IQR 16–37). At a median follow-up of 29 months (IQR 20...

PURPOSE To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL). METHODS We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050 ). RESULTS We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age > 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases. CONCLUSION The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL.

IntroductionCNS dissemination in patients with aggressive non-Hodgkin lymphoma (NHL) is a relatively rare but often fatal complication that occurs in the different subtypes of NHL with a frequency of 5% (ie, diffuse large B-cell lymphoma [DLBCL]) to 30% 1 (ie, Burkitt lymphoma [BL] and B-cell lymphoblastic lymphoma [B-LL]). Many CNS events occur early after diagnosis (4.7-9 months), during therapy, or shortly after completion of treatment, suggesting that initial CNS involvement could have been undetected in most cases. Prophylactic treatment likely reduces the incidence of CNS relapse, but may increase the toxicity of systemic chemotherapy; furthermore, the incidence of CNS dissemination is not high enough to suggest the use of prophylaxis treatment in all patients affected by aggressive NHL. Therefore, CNS prophylaxis is usually incorporated into protocols for the treatment of B-LL and BL, but it is not systematically warranted in patients with DLBCL. Therefore, the identification of patient subgroups for which CNS prophylaxis may be useful is important, especially for DLBCL patients who have no well-defined risk factors for CNS relapse. Risk models for DLBCL have been developed, but are mainly derived from analyses of retrospective studies. [2][3][4][5] An increased risk of CNS dissemination is associated with involvement of the BM and certain extranodal sites such as testis, paranasal sinuses, orbits, and paravertebral masses. Moreover, patients with a high to intermediate or high risk according to the International Prognostic Index (IPI), particularly those with high serum levels of lactate dehydrogenase (LDH) and involvement of more than 1 extranodal organ, are much more prone to develop CNS involvement than others and should receive CNS prophylaxis. 6 Nevertheless, CNS risk predictors and related prognostic scores have been identified in retrospective and heterogeneous series, including different lymphoma categories; however, resulting scores show a low sensitivity in predicting CNS involvement.The diagnosis of CNS dissemination is frequently suspected by the presence of related signs or symptoms and confirmed by examination of cerebrospinal fluid (CSF) and neuroimaging techniques. The diagnostic standard conventional cytology (CC) examination of CSF is considered as having low sensitivity and low specificity, with reported falsenegative rates of 20%-60%. 7 This has been ascribed to the paucity of neoplastic cells in the CSF of patients with minimal disease and to the presence of confounding reactive lymphocytes. Therefore, patients with low tumor burden in the CSF, who are more likely to benefit from CNS treatment, are actually more commonly exposed to false-negative [8][9][10][11][12][13][14] However, it is still unknown whether detecting occult leptomeningeal involvement and consequently changing treatment may improve outcome in these patients.In the present study, we compared prospectively FCM analysis versus CC examination of baseline samples of CSF to detect occult leptomeningeal disease in patie...