The importance of secondary cancer screening programs in Hodgkin lymphoma survivors.

Not available.

Plasma neurofilament light chain levels in chemotherapy-induced peripheral neurotoxicity according to type of anticancer drug.

BACKGROUND AND PURPOSE: A real-time biomarker in chemotherapy-induced peripheral neurotoxicity (CIPN) would be useful for clinical decision-making during treatment. Neurofilament light chain (NfL) can be detected in blood in the case of neuroaxonal damage. The aim of the study was to compare the levels of plasma NfL (pNfL) according to the type of chemotherapeutic agent and the severity of CIPN. METHODS: This single-center prospective observational longitudinal study included patients treated with paclitaxel (TX; n = 34), brentuximab vedotin (BV; n = 29), or oxaliplatin (PT; n = 19). All patients were assessed using the Total Neuropathy Score-clinical version and Common Terminology Criteria for Adverse Events before, during, and up to 6-12 months after the end of treatment. Nerve conduction studies (NCS) were performed before and after chemotherapy discontinuation. Consecutive plasma samples were analyzed for NfL levels using a Simoa® analyzer. Changes in pNfL were compared between groups and were eventually correlated with clinical and NCS data. Clinically relevant (CR) CIPN was considered to be grade ≥ 2. RESULTS: Eighty-two patients, mostly women (59.8%), were included. One third of the patients who received TX (29.4%), BV (31%), or PT (36.8%) developed CR-CIPN, respectively, without differences among them (p = 0.854). Although pNfL significantly increased during treatment and decreased throughout the recovery period in all three groups, patients receiving TX showed significantly greater and earlier changes in pNfL levels compared to the other agents (p < 0.001). CONCLUSIONS: A variable change in pNfL is observed depending on the type of agent and mechanism of neurotoxicity with comparable CIPN severity, strongly implying the need to identify different cutoff values for each agent.

Peripheral T-cell lymphoma with a T follicular-helper phenotype: A different entity? Results of the Spanish Real-T study.

Nodal peripheral T-cell lymphoma (PTCL) with a T follicular helper phenotype (PTCL-TFH) is a new type of PTCL. We aimed to define its clinical characteristics and prognosis compared to PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL). This retrospective observational study included 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. Patient diagnosis was centrally reviewed, and patients were reclassified according to the World Health Organization (WHO) 2016 criteria: 21 patients as PTCL-NOS, 55 as AITL and 23 as PTCL-TFH. Median follow-up was 56.07 months (95% CI 38.7-73.4). Progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with PTCL-TFH than in those with PTCL-NOS and AITL (PFS, 24.6 months vs. 4.6 and 7.8 months, respectively, p = 0.002; OS, 52.6 months vs. 10.0 and 19.3 months, respectively, p < 0.001). Histological diagnosis maintained an independent influence on both PFS (hazard ratio [HR] 4.1 vs. PTCL-NOS, p = 0.008; HR 2.6 vs. AITL, p = 0.047) and OS (HR 5.7 vs. PTCL-NOS, p = 0.004; HR 2.6 vs. AITL, p = 0.096), regardless of the International Prognostic Index. These results suggest that PTCL-TFH could have more favourable features and prognosis than the other PTCL subtypes, although larger series are needed to corroborate these findings.

Anti-CD30 antibody-drug conjugate therapy in lymphoma: current knowledge, remaining controversies, and future perspectives.

CD30 is overexpressed in several lymphoma types, including classic Hodgkin lymphoma (cHL), some peripheral T-cell lymphomas (PTCL), and some cutaneous T-cell lymphomas. The antibody-drug conjugate brentuximab vedotin targets CD30-positive cells and has been evaluated for the treatment of various lymphoma entities. This narrative review summarizes 10 years of experience with brentuximab vedotin for the treatment of CD30-positive lymphomas, discusses novel therapies targeting CD30 in development, and highlights remaining controversies relating to CD30-targeted therapy across lymphoma types. The collective body of evidence for brentuximab vedotin demonstrates that exploitation of CD30 can provide sustained benefits across a range of different CD30-positive lymphomas, in both clinical trials and real-world settings. Preliminary experience with brentuximab vedotin in combination with immune checkpoint inhibitors for relapsed/refractory cHL is encouraging, but further exploration is required. The optimal use of brentuximab vedotin for first-line therapy of PTCL remains to be determined. Further research is required on brentuximab vedotin treatment in high-risk patient populations, and in rare lymphoma subtypes, for which no standard of care exists. Novel therapies targeting CD30 include chimeric antigen receptor therapies and bispecific antibody T-cell engagers, which may be expected to further improve outcomes for patients with CD30-positive lymphomas in the coming years.

Impact of pre- and/or post-autologous stem cell transplantation exposure to brentuximab vedotin on survival outcomes in patients with high-risk Hodgkin lymphoma.

The AETHERA trial demonstrated that brentuximab vedotin (BV) consolidation after autologous stem cell transplantation (ASCT) in patients with Hodgkin lymphoma (HL) at high risk of relapse/progression increases progression-free survival (PFS). Patients previously exposed to BV were excluded from that trial. However, BV alone or in combination with chemotherapy is frequently used as front-line treatment and/or pre-ASCT salvage therapy. We analyzed data from 156 patients with high-risk HL who underwent ASCT with (BV-CON, n = 62) or without (non-BV, n = 94) BV consolidation. Fifty-seven patients received BV-based salvage regimens before ASCT. The 3-year overall survival and PFS for all patients were 91.6% and 70.0%, respectively. Multivariate analysis showed that BV-CON was associated with better PFS (HR 0.39, p = 0.01), whereas positive PET at transplant leaded to worse PFS (HR 2.71, p = 0.001). BV-CON improved PFS in PET-positive patients (72.2% vs. 43.0%, p = 0.05), with a beneficial trend observed in PET negative (88.8% vs. 75.2%, p = 0.09). BV-CON patients with or without BV exposure pre-ASCT had a significantly better PFS than non-BV with or without BV pretransplant treatment (HR 0.36, p = 0.004). The efficacy of real-life BV consolidation therapy was similar to that in the AETHERA trial. This therapeutic strategy improves survival independently of BV exposure prior to ASCT.

A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma.

In relapsed/refractory Hodgkin lymphoma (R/R HL), immunotherapies such as the anti-programmed death-1 inhibitor pembrolizumab have demonstrated efficacy as monotherapy and are playing an increasingly prominent role in treatment. The CD30/CD16A-bispecific antibody AFM13 is an innate immune cell engager, a first-in-class, tetravalent antibody, designed to create a bridge between CD30 on HL cells and the CD16A receptor on natural killer cells and macrophages, to induce tumor cell killing. Early studies of AFM13 have demonstrated signs of efficacy as monotherapy for patients with R/R HL and the combination of AFM13 with pembrolizumab represents a rational new treatment modality. Here, we describe a phase 1b, dose-escalation study to assess the safety and preliminary efficacy of AFM13 in combination with pembrolizumab in patients with R/R HL. The primary objective was estimating the maximum tolerated dose; the secondary objectives were to assess safety, tolerability, antitumor efficacy, pharmacokinetics, and pharmacodynamics. In this heavily pretreated patient population, treatment with the combination of AFM13 and pembrolizumab was generally well tolerated, with similar safety profiles compared to the known profiles of each agent alone. The combination of AFM13 with pembrolizumab demonstrated an objective response rate of 88% at the highest treatment dose, with an 83% overall response rate for the overall population. Pharmacokinetic assessment of AFM13 in the combination setting revealed a half-life of up to 20.6 hours. This proof-of-concept study holds promise as a novel immunotherapy combination worthy of further investigation. This phase 1b study was registered at www.clinicaltrials.gov as NCT02665650.

Clonal relationship in multisited mucosa-associated lymphoid tissue lymphomas: a single-centre experience.

Clonal heterogeneity in multisited or recurrent lymphoid neoplasms is a phenomenon that has been increasingly studied in recent years. However, in mucosa-associated lymphoid tissue (MALT) lymphomas it remains largely unexplored. Patients diagnosed at our institution with multisited MALT lymphoma, from January 2009 to October 2018, were studied. Molecular studies were performed for the detection of clonally rearranged immunoglobulin by polymerase chain reaction.In all, 91 patients were included. Of those, 28 had a multisited disease and in 16 clonality studies were done. In eight cases, multifocal involvement was synchronous and in eight metachronous. Patients with non-gastric gastrointestinal tract involvement tended to disseminate within the same tract, without observing other specific dissemination patterns. Four cases (25%) had clonal heterogeneity at the different organs involved. All patients with late relapses (two patients) had different clones. The majority of patients with multisited MALT lymphomas presented with the same clone in the different involved organs, identifying a different clone in those with late relapses. These patients could represent de novo neoplasms, rather than a relapse. This could mean that some individuals might have a genetic predisposition to develop this type of lymphoma and it could also have clinical implications regarding therapeutic decisions.

Clinical and pathological characteristics of peripheral T-cell lymphomas in a Spanish population: a retrospective study.

We investigated the clinicopathological features and prognostic factors of patients with peripheral T-cell lymphoma (PTCL) in 13 sites across Spain. Relevant clinical antecedents, CD30 expression and staining pattern, prognostic indices using the International Prognostic Index and the Intergruppo Italiano Linfomi system, treatments, and clinical outcomes were examined. A sizeable proportion of 175 patients had a history of immune-related disorders (autoimmune 16%, viral infections 17%, chemo/radiotherapy-treated carcinomas 19%). The median progression-free survival (PFS) and overall survival (OS) were 7·9 and 15·8 months, respectively. Prognostic indices influenced PFS and OS, with a higher number of adverse factors resulting in shorter survival (P < 0·001). Complete response (CR) to treatment was associated with better PFS (62·6 vs. 4 months; P < 0·001) and longer OS (67·0 vs. 7·3 months; P < 0·001) compared to no CR. CD30 was expressed across all subtypes; >15% of cells were positive in anaplastic lymphoma kinase-positive and -negative anaplastic large-cell lymphoma and extranodal natural killer PTCL groups. We observed PTCL distribution across subtypes based on haematopathological re-evaluation. Poor prognosis, effect of specific prognostic indices, relevance of histopathological sub-classification, and response level to first-line treatment on outcomes were confirmed. Immune disorders amongst patients require further examination involving genetic studies and identification of associated immunosuppressive factors.

Long-term follow-up of a prospective phase 2 clinical trial of extended treatment with rituximab in patients with B cell post-transplant lymphoproliferative disease and validation in real world patients.

The purpose of this report is to provide long-term follow-up of 38 patients diagnosed of post-transplant lymphoproliferative disease (PTLD) included in a phase 2 clinical trial of first line therapy with rituximab and to evaluate the same therapy in a real world cohort of 21 consecutive patients treated once the trial was closed. Eligible patients were ≥ 18 years of age with a biopsy-proven CD20 positive B cell PTLD and treatment naive except for reduction of immunosuppression. Treatment consisted in four weekly infusions of rituximab at the standard dose of 375 mg/m2. Patients in complete remission (CR) were followed without further treatment, and those in partial remission (PR) were treated with another four cycles of weekly rituximab. Median follow-up in the clinical trial was 13.0 years. Disease-specific survival (DSS) at 10 years was 64.7% [95% confidence interval (CI) 48.2-81.2%]. For those patients who achieved CR (61%), DSS at 5 and 10 years was 94.4% (95% CI 83.8-100%) and 88.1% (95% CI 72.6-100%), respectively, and only 1 patient progressed beyond 5 years. The median follow-up of the real world patients was 6.5 years. DSS at 5 years was 75.2% (95% CI 56.4-94.0%). DSS at 5 years of patients who achieved CR (38%) was 87.5% (95% CI 64.6-100%). In conclusion, PTLD patients in CR after rituximab have an excellent long-term outcome. These results not only apply in the clinical trial setting but are also reproducible in the real world. However, those patients who do not respond represent an unmet clinical need and should be included in prospective clinical trials.

Inappropriate Empirical Antibiotic Treatment in High-risk Neutropenic Patients With Bacteremia in the Era of Multidrug Resistance.

BACKGROUND: We aimed to describe the current rates of inappropriate empirical antibiotic treatment (IEAT) in oncohematological patients with febrile neutropenia (FN) and its impact on mortality. METHODS: This was a multicenter prospective study of all episodes of bloodstream infection (BSI) in high-risk FN patients (2006-2017). Episodes receiving IEAT were compared with episodes receiving appropriate empirical therapy. Adherence to Infectious Diseases Society of America (IDSA) recommendations was evaluated. Multivariate analysis was performed to identify independent risk factors for mortality in Pseudomonas aeruginosa episodes. RESULTS: Of 1615 episodes, including Escherichia coli (24%), coagulase-negative staphylococci (21%), and P. aeruginosa (16%), 394 (24%) received IEAT despite IDSA recommendations being followed in 87% of cases. Patients with multidrug-resistant gram-negative bacilli (MDR-GNB), accounting for 221 (14%) of all isolates, were more likely to receive IEAT (39% vs 7%, P < .001). Overall mortality was higher in patients with GNB BSI who received IEAT (36% vs 24%, P = .004); when considering individual microorganisms, only patients with infection caused by P. aeruginosa experienced a significant increase in mortality when receiving IEAT (48% vs 31%, P = .027). Independent risk factors for mortality in PA BSI (odds ratio [95% confidence interval] were IEAT (2.41 [1.19-4.91]), shock at onset (4.62 [2.49-8.56]), and pneumonia (3.01 [1.55-5.83]). CONCLUSIONS: IEAT is frequent in high-risk patients with FN and BSI, despite high adherence to guidelines. This inappropriate treatment primarily impacts patients with P. aeruginosa-related BSI mortality and in turn is the only modifiable factor to improve outcomes.

Potential Survival Benefit for Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation after Nivolumab Therapy for Relapse/Refractory Hodgkin Lymphoma: Real-Life Experience in Spain.

Clinical trials have shown that nivolumab has remarkable activity against relapsed/refractory classical Hodgkin lymphoma (cHL). However, the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) as consolidation therapy in these patients remains controversial. We performed a retrospective analysis of data from 74 patients treated with nivolumab. The overall response rate was 58% (including 30.6% with complete responses). Treatment-related adverse events were reported in 56.8% of patients (grade ≥3 in 9.4%). The main reasons for nivolumab discontinuation were referral for transplantation (41.7% patients) and disease progression (37.5%). The 2-year overall survival (OS) rate was 52% for the entire series. Ultimately, 39 patients underwent allo-HSCT. The cumulative incidence of grade II-IV acute graft-versus-host disease was 33.3% (grade III-IV in 2 patients). The cumulative incidence of nonrelapse mortality was 13.2%. Among the patients who responded to nivolumab, the 2-year OS and progression-free survival (PFS) were higher in patients who underwent consolidation with allo-HSCT (77.5% versus 42.6% [P = .126] and 73.9% versus 27.2% [P = .025], respectively). Thus, the efficacy and safety of nivolumab were comparable to values reported in previous clinical trials. The percentage of patients who bridged to transplantation was high, indicating a preference for Spanish physicians. These results suggest that consolidation allo-HSCT increases OS and PFS.

Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial.

BACKGROUND: Based on the encouraging activity and manageable safety profile observed in a phase 1 study, the ECHELON-2 trial was initiated to compare the efficacy and safety of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for the treatment of CD30-positive peripheral T-cell lymphomas. METHODS: ECHELON-2 is a double-blind, double-dummy, randomised, placebo-controlled, active-comparator phase 3 study. Eligible adults from 132 sites in 17 countries with previously untreated CD30-positive peripheral T-cell lymphomas (targeting 75% with systemic anaplastic large cell lymphoma) were randomly assigned 1:1 to receive either A+CHP or CHOP for six or eight 21-day cycles. Randomisation was stratified by histological subtype according to local pathology assessment and by international prognostic index score. All patients received cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 on day 1 of each cycle intravenously and prednisone 100 mg once daily on days 1 to 5 of each cycle orally, followed by either brentuximab vedotin 1·8 mg/kg and a placebo form of vincristine intravenously (A+CHP group) or vincristine 1·4 mg/m2 and a placebo form of brentuximab vedotin intravenously (CHOP group) on day 1 of each cycle. The primary endpoint, progression-free survival according to blinded independent central review, was analysed by intent-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01777152. FINDINGS: Between Jan 24, 2013, and Nov 7, 2016, 601 patients assessed for eligibility, of whom 452 patients were enrolled and 226 were randomly assigned to both the A+CHP group and the CHOP group. Median progression-free survival was 48·2 months (95% CI 35·2-not evaluable) in the A+CHP group and 20·8 months (12·7-47·6) in the CHOP group (hazard ratio 0·71 [95% CI 0·54-0·93], p=0·0110). Adverse events, including incidence and severity of febrile neutropenia (41 [18%] patients in the A+CHP group and 33 [15%] in the CHOP group) and peripheral neuropathy (117 [52%] in the A+CHP group and 124 [55%] in the CHOP group), were similar between groups. Fatal adverse events occurred in seven (3%) patients in the A+CHP group and nine (4%) in the CHOP group. INTERPRETATION: Front-line treatment with A+CHP is superior to CHOP for patients with CD30-positive peripheral T-cell lymphomas as shown by a significant improvement in progression-free survival and overall survival with a manageable safety profile. FUNDING: Seattle Genetics Inc, Millennium Pharmaceuticals Inc, a wholly owned subsidiary of Takeda Pharmacuetical Company Limited, and National Institutes of Health National Cancer Institute Cancer Center.

Long-term outcome comparing histological grades of follicular lymphoma patients treated with immunochemotherapy as first-line therapy: A retrospective analysis from two institutions.

OBJECTIVES: To clarify the impact of histological grades in follicular lymphoma. METHODS: We retrospectively analysed 250 patients diagnosed with FL treated with chemoimmunotherapy: 188 patients were grades 1-2 and 62 grade 3A. RESULTS: In our series, grade 3A FL patients were older, higher proportion of localised disease and lower bone marrow infiltration at diagnosis comparing grades 1-2 FL patients. Estimated six-year progression-free survival and time to progression showed no differences between both groups [grade 3A: 56% (95%CI: 39%-73%) and 51% (95%CI: 41%-61%) vs grades 1-2:55% (95%CI: 46%-63%) and 57% (95%CI: 49%-65%), P = .782 and P = .521, respectively]. Estimated six-year overall survival was lower, 76% (95%CI: 64%-88%) for the grade 3A group than grades 1-2 83% (95%CI: 77%-89%); P = .044. In addition to that, cumulative incidence curves of death not related to lymphoma at 10 years between groups were as follows: [0.26 (95%CI: 0.25-0.27) and 0.05 (95%CI: 0.04-0.06) for G3AFL and G1-2FL, respectively], P = .010. Grade 3A FL showed in PFS curve no relapses after 6 years. These results were absolutely reproduced in 199 patients receiving R-CHOP regimen as induction. CONCLUSIONS: Our results indicate similar long-term outcomes in terms of progression-free survival and time to progression in grades 1-2 and 3A. No relapses were observed in G3AFL group after 6 years.

m7FLIPI and targeted sequencing in high-risk follicular lymphoma.

Patients with follicular lymphoma (FL) refractory to front-line immunochemotherapy (ICT) have a poor overall survival (OS). Gene mutation analysis may be more accurate than classical risk factors to pick out these patients before treatment. This study aimed to describe the prevalence of selected genetic mutations in a cohort of patients with high-risk FL. Twenty-five patients with FL refractory to front-line ICT and 10 non-refractory patients matched for age, sex, and FLIPI score were included. We sequenced 18 genes (custom targeted sequencing panel) previously reported to potentially have prognostic impact, including the seven genes necessary to determine m7FLIPI risk. The 35 patients had a median age of 62. The FLIPI and FLIPI2 were high in 27 (84%) and 14 (48%), respectively. Three-year progression-free survival (PFS) and OS probabilities were 25% (95% CI, 13%-41%) and 53% (34%-69%), respectively. There were 73 variants in the 18 genes among the 35 patients. The median number of mutations per patient was 1 (interquartile range, 0-3). The most commonly mutated genes were CREBBP (11 of 35, 31%) and EP300 (10 of 35, 29%). EP300 mutations were associated with refractoriness to treatment (10 of 25 among refractory and 0 of 10 among non-refractory). In conclusion, in this study, patients with high-risk follicular lymphoma were genetically heterogeneous.

Long-term safety and outcome of fludarabine, cyclophosphamide and mitoxantrone (FCM) regimen in previously untreated patients with advanced follicular lymphoma: 12 years follow-up of a phase 2 trial.

Fludarabine combinations are very affective in follicular lymphoma (FL) with high rates of complete response and prolonged survival. However, late toxicities could be a concern. The aim of the present study was to analyze the long-term impact on survival, relapse and late toxicities of a trial of treatment with fludarabine, mitoxantrone and cyclophosphamide (FCM regimen) for untreated patients with advanced stage FL. One hundred and twenty patients enrolled in a phase 2 trial of treatment with FCM regimen between 2000 and 2003 were evaluated. After a median follow-up of 12 years, 52 patients eventually relapsed/progressed with 10 year progression-free survival (PFS) of 46 %. Ten patients showed histological transformation to aggressive lymphoma with a risk of transformation of 2 and 9 % at 5 and 10 years, respectively. Three patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) and seven solid neoplasms with an overall risk of 3 and 8 % at 5 and 10 years, respectively. Twenty-six patients eventually died during the follow-up. Overall survival at 10 years was 83 %. In conclusion, FCM regimen allows excellent long-lasting response in previously untreated patients with FL. The incidence of late events including histological transformation and secondary neoplasia is low but not negligible.

Phase II trial of ofatumumab plus ESHAP (O-ESHAP) as salvage treatment for patients with relapsed or refractory classical Hodgkin lymphoma after first-line chemotherapy.

The management of recurrent/refractory (R/R) Hodgkin lymphoma (HL) remains challenging. Previously published data have shown some efficacy of rituximab in this setting. The purpose of this phase II trial was to investigate the activity of ofatumumab in combination with etoposide, steroids, cytarabine and cisplatin (O-ESHAP) in 62 patients with R/R classical HL. Treatment consisted of ESHAP plus ofatumumab 1000 mg on days 1 and 8 of the first cycle and day 1 of the second and third cycles. O-ESHAP was well tolerated with only 3% of patients requiring treatment discontinuation because of adverse events. Overall response rate was 73% (44% complete metabolic response). In multivariate analysis, early relapse (P < 0·001), bulky disease (P < 0·001) and B symptoms (P < 0·001) were the most important prognostic factors for response. No failures of stem cell mobilization were observed. The high response rate, particularly the complete metabolic response rate, the low toxicity profile, and the high mobilizing potential of the O-ESHAP regimen suggest that patients with R/R HL may benefit from this salvage regimen. However, with the encouraging results observed with other new therapeutic agents in HL, the O-ESHAP regimen could be restricted to patients failing these agents or to those with R/R nodular lymphocyte-predominant HL.

Long-Term Follow-Up of a Phase II Trial of Six Cycles of Dose-Dense R-CHOP-14 for First-Line Treatment of Diffuse Large B-Cell Lymphoma in Young and Elderly Patients.

BACKGROUND/AIMS: Rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 14 days seems to achieve better outcomes than R-CHOP every 21 days in diffuse large B-cell lymphoma (DLBCL) patients. Currently, the standard regimen is R-CHOP every 21 days. METHODS: This is a phase II clinical trial of treatment with 6 cycles of R-CHOP-14 with pegfilgrastim support in 2 populations of previously untreated DLBCL patients aged ≥65 years (n = 73) or <65 years (n = 51) with low-risk International Prognostic Index scores (0-2). RESULTS: With a median follow-up of 63.7 months, the 5-year event-free survival rate was 53.8% in patients aged ≥65 years and 71.0% in patients aged <65 years. The 5-year overall survival rate was 71.4 and 89.8%, respectively. The complete remission rate was 69.9% for older and 80.4% for younger patients. The median relative dose intensity of cytotoxic drugs was 143.2% in the elderly and 149.1% in the young patients. Febrile neutropenia was the most common grade 3-4 adverse event, being higher in elderly patients (21.3 vs. 9.3%). Eight deaths (7 in elderly patients) were considered treatment related. CONCLUSION: In conclusion, the R-CHOP-14 regimen is feasible and very active, though it is more toxic in elderly patients mainly due to an increased incidence of infections. New strategies, such as new monoclonal antibodies or new targeted therapies, are needed to improve the outcomes of DLBCL patients.