Search

Although follicular lymphoma (FL) patients relapsing within 24 months after first-line treatment (POD24) have a poor prognosis, some cases show notable survival after first relapse (SF1R). We aimed to characterize the POD24 FL population and to identify the main prognostic factors at progression. We selected 162 POD24 patients (80F; median age at first relapse 59 years) from a cohort of 1067 grades 1-3a FL-treated patients. The remaining 905 patients treated with first-line immunochemotherapy and diagnosed during the same period were used to compare outcomes in terms of survival. After a median follow-up of 11.0 years, 96 patients died (10y-SF1R of 40%). Age over 60 years (p 0.001), high lactate dehydrogenase (LDH) (p 0.001), haemoglobin (Hb) less than 120 g/L (p 0.001), advanced stage (p 0.001), high-risk Follicular Lymphoma International Prognostic Index (FLIPI) (p 0.001), histological transformation (HT) (p0.001) and reaching less than complete response (CR) after salvage therapy (p 0.001), predicted poor SF1R at relapse. In multivariate analysis only high-risk FLIPI and HT maintained prognostic significance for SF1R. POD24 patients not transformed and with low/intermediate FLIPI at relapse behaved better than the remaining cases. POD24 patients showed an excess mortality of 38% compared to the general population. Although outcome of POD24 FL patients is poor, a considerable group of them (low/intermediate FLIPI and not transformed at first relapse) behave better.

This retrospective study evaluated 66 patients diagnosed with relapsed and/or refractory mantle cell lymphoma (R/R MCL) treated with ibrutinib in Spain in routine clinical practice. At diagnosis, patients had a median age of 64.5 years, 63.6% presented with intermediate/high sMIPI (simplified prognostic index for advanced-stage mantle cell lymphoma), 24.5% had the blastoid variant, and 55.6% had a Ki67 > 30%. Patients had received a median of 2 prior lines of therapy (range 1-2; min-max 1-7). Overall response rate was 63.5%, with 38.1% of patients achieving complete response (CR). With a median duration of ibrutinib exposure of 10.7 months (range 5.2-19.6; min-max 0.3-36), the median progression-free survival (PFS) and overall survival (OS) were 20 months [95% confidence interval (CI) 8.8-31.1] and 32 months (95% CI 22.6-41.3), respectively, and were not reached in patients achieving CR. No grade >= 3 cardiovascular toxicity or bleeding was reported. This study supports that treatment with ibrutinib leads to high response rates and favorable survival outcomes in patients with R/R MCL.

To design and implement a plan to improve oncohaematological patients' sleep.The hospital environment can compromise inpatients' sleep, negatively impacting on health outcomes and patient satisfaction.The improvement plan was designed in collaboration with 18 professionals, 3 patients and 3 accompanying relatives. The study designed followed the SQUIRE 2.0 guidelines. Outcome variables were self-reported patient satisfaction regarding sleep, measured using a 30-item, ad hoc questionnaire and a 10-point visual analogue scale, completed by 318 oncohaematological inpatients (pre-intervention n = 120, post-intervention, n = 198) in a comprehensive cancer centre in Spain from 2017 to 2019.Overall, 61.5% (n = 190) of the inpatients reported sleep alterations, and 92.6% reported interruptions in their nightly sleep. Half slept less than 6 h/night, but 58.0% said they felt rested upon waking, despite the interruptions. These outcomes were similar before and after the intervention. The improvement plan identified four domains for work (professionals, care procedures, instruments/environment and patients/relatives), 10 areas for improvement and 35 actions for implementation. However, overall sleep worsened significantly, from 6.73 to 6.06 on the 10-point scale. The intervention significantly improved variables related to professionals' behaviour, including noise during the shift change, conversations at the control desk and the use of corridor lights. Sleep disturbances were mainly caused by pain/discomfort and infuser alarms, and collectively they decreased significantly after the intervention (p = .008). However, overall sleep worsened significantly, from 6.73 to 6.06 on the 10-point scale.Pain, clinical devices and noise made by professionals are the main causes of sleep disturbances. Involving professionals in decision-making to improve patients' sleep have a positive impact on noise levels.This study proposes new strategies for improving sleep by increasing staff awareness and changing attitudes towards patients' sleep. Nurses should be involved in addressing sleep disturbances during hospitalization.

INTRODUCTION: This double-blind, parallel-group, active-controlled phase III trial (NCT02260804) assessed CT-P10 and rituximab safety and efficacy in patients with previously untreated low-tumor-burden follicular lymphoma (LTBFL), including after a single switch from rituximab to CT-P10. PATIENTS AND METHODS: LTBFL patients were randomized (1:1) to receive CT-P10 or rituximab (375 mg/m(2) intravenously; day 1 of 4 7-day cycles). Patients achieving disease control entered a 2-year maintenance period. CT-P10 or rituximab were administered every 8 weeks (6 cycles) in year 1; all patients could receive CT-P10 (every 8 weeks; 6 cycles) in year 2. Secondary endpoints (reported here) were overall response rate (ORR) during the study period, progression-free survival (PFS), time to progression (TTP), and overall survival (OS). Safety and immunogenicity were evaluated. RESULTS: Between November 9, 2015 and January 4, 2018, 258 patients were randomized (130 for CT-P10; 128 for rituximab). ORR was similar between groups over the study period (CT-P10: 88%; rituximab: 87%). After 29.2 months' median follow-up, median PFS, TTP, and OS were not estimable; 24-month Kaplan-Meier estimates suggested similarity between groups. Overall, 114 (CT-P10: 88%), and 104 (rituximab: 81%) patients experienced treatment-emergent adverse events. The single switch was well tolerated. CONCLUSION: These updated data support therapeutic similarity of CT-P10 and rituximab and support the use of CT-P10 monotherapy for previously untreated LTBFL.

Rituximab biosimilars are a cornerstone of treatment of advanced-stage follicular lymphoma (FL). This double-blind, parallel-group, phase 3 trial randomized (1:1) adults (≥18 years) with stage III to IV indolent B-cell lymphoma, including grades 1 to 3a FL, to receive CT-P10 or rituximab (375 mg/m2 IV), with cyclophosphamide, vincristine, and prednisone, every 3 weeks for 8 cycles (induction period). Patients achieving complete response (CR), unconfirmed CR, or partial response (PR) received CT-P10 or rituximab maintenance for 2 years (375 mg/m2, every 8 weeks). Primary end points were previously reported, proving noninferiority of efficacy and pharmacokinetic equivalence of CT-P10 to rituximab. Secondary end points included overall response rate (PR+CR) during the induction period per 2007 International Working Group (IWG) criteria, survival analyses, and overall safety. Between 28 July 2014 and 29 December 2015, 140 patients were randomized (70 per group). Median follow-up was 39.9 months (interquartile range, 36.7-43.5). Per 1999 IWG criteria, 4-year Kaplan-Meier estimates (95% confidence interval [CI]) for CT-P10 and rituximab were 61% (47% to 73%) and 55% (36% to 70%) for progression-free survival (hazard ratio, 1.33 [95% CI, 0.67-2.63]; P=.409), respectively, and 88% (77% to 94%) and 93% (83% to 97%) for overall survival (5.29 [0.84-33.53]; P=.077). Overall, 90% (CT-P10) and 86% (rituximab) of patients experienced treatment-emergent adverse events. Long-term safety profiles were similar between groups. Findings confirm favorable outcomes for CT-P10–treated patients with advanced-stage FL and demonstrate comparable long-term efficacy and overall safety between CT-P10 and rituximab. This trial was registered at www.clinicaltrials.gov as #NCT02162771.

Primary effusion lymphoma (PEL) is a rare non-Hodgkin lymphoma confined exclusively to body cavities without detectable tumor masses. The term PEL-like is an entity similar to PEL in clinical presentation but without relation to human herpesvirus 8 (HHV8). We report a case of HHV8- and EBV-negative primary effusion-based lymphoma.

High-quality data on bone marrow involvement (BMI) assessed by flow cytometry (FC) in follicular lymphoma (FL) is lacking.We set up a prospective protocol with a 10-color tube and acquisition of 500.000 leukocytes on a Nav flow cytometer for evaluation of BMI in FL by FC.FC was compared with a combination of histopathology and IGH gene rearrangement, which were considered the gold standard. We also compared BMI by FC with PET.Fifty-two patients were included (median 67 years, 54% female). BMI by FC was seen in 35 (67%), with a median involvement of 1.2% (interquartile range: 0.3%-7%) of leukocytes. Comparison with the gold standard revealed two false negatives and two false positives (potentially true involvement undetected by the gold standard). BMI by PET was seen in 14/46 (30%). Immunophenotype of FL in the bone marrow was highly heterogeneous. The most common phenotypic abnormality was dim expression of CD19 (0.5 log loss in 30% of patients). CD10 was negative in 13 (37%) and incompletely positive (overlap with the negative population) in a further 8 (28%) while entirely positive only in 14 (48%). Other abnormalities (loss of CD20, gain or loss of CD79b, expression of CD43, and substantial loss of CD45) were rare. Computational analysis by means of FlowSOM confirmed the heterogeneous phenotype, with FL from different patients clustering in unrelated metaclusters.BMI by FL was frequent and immunophenotype was heterogeneous. However, this protocol enabled detection of FL in bone marrow in the vast majority of patients with bone marrow involvement by the gold standard.

Mantle cell lymphoma (MCL) after relapse is associated with poor prognosis. No standard of care exists and available evidence for treatments is limited, particularly in patients who fail Bruton tyrosine kinase inhibitor (BTKi) therapy. This multicentre retrospective chart review study, SCHOLAR-2, addresses this knowledge gap and reports on data collected from 240 patients with relapsed/refractory MCL in Europe who were treated with BTKi-based therapy between July 2012 and July 2018, and had experienced disease progression while on BTKi therapy or discontinued BTKi therapy due to intolerance. The median overall survival (OS) from initiation of first BTKi therapy was 14.6 months (95% confidence interval [CI] 11.6-20.0) in the overall cohort, 5.5 months (95% CI 3.9-8.2) in 91 patients without post-BTKi therapy, and 23.8 months (95% CI 18.9-30.1) in 149 patients who received post-BTKi therapy (excluding chimeric antigen receptor T-cell treatment). In the latter group, patients received a median of one (range, one to seven) line of post-BTKi therapy, with lenalidomide-containing regimens and bendamustine plus rituximab being the most frequently administered; the median OS from initiation of first post-BTKi therapy was 9.7 months (95% CI 6.3-12.7). These results provide a benchmark for survival in patients with R/R MCL receiving salvage therapy after BTKi failure.

This is a randomized phase-2 trial aimed to compare consolidation vs. maintenance in untreated patients with follicular lymphoma (FL) responding to induction. 146 patients were enrolled from 25 Spanish institutions (ZAR2007; ClinicalTrials.gov #NCT00662948). Patients in PR or CR/CR[u] after R-CHOP were randomized 1:1 to 90Y-ibritumomab-tiuxetan 0.4 mCi/kg (arm A) vs. rituximab 375 mg/m2 every 8 weeks for 2 years (arm B). After a median follow-up of 10.55 years, 53 patients eventually progressed with a 10-year PFS of 50% vs. 56% for patients in arm A and B, respectively (HR = 1.42; p > 0.1). No significant differences were seen in OS (10-year OS 78% vs. 84.5%; HR = 1.39, p > .1). Patients receiving 90Y-ibritumomab-tiuxetan showed higher incidence of second neoplasms than those in arm B (10-year cumulative incidence 18.5 vs. 2%, respectively; p = .038). In conclusion, in FL patients responding to R-CHOP, no significant differences were found between consolidation and maintenance, although with higher late toxicity for consolidation.

Patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) have a poor prognosis and a median overall survival of less than 6 months. Outcomes and responses were evaluated in 134 patients with DLBCL administered selinexor. Our findings demonstrate that selinexor treatment in DLBCL patients can safely induce durable responses and improve outcomes regardless of prior treatments and refractory status. Background: Despite a number of treatment options, patients with diffuse large B-cell lymphoma (DLBCL) whose disease has become refractory to treatment have a poor prognosis. Selinexor is a novel, oral drug that is approved to treat patients with relapsed/refractory DLBCL. In this post hoc analysis of the SADAL study, a multinational, open-label study, we evaluated subpopulations to determine if response to single agent selinexor is impacted by number of lines of prior treatment, autologous stem cell transplant (ASCT), response to first and most recent therapies, and time to progressive disease. Patients: Patients (n = 134) with DLBCL after 2-5 prior therapies were enrolled in SADAL and received 60mg selinexor twice weekly. Results: The median overall survival was 9.0 months and median progression free survival was 2.6 months. Patients who had the best overall response rate (ORR) and disease control rate were those who had prior ASCT (42.5% and 50.0%) or responded to last line of therapy (35.9% and 43.5%). Patients with primary refractory DLBCL also showed responses (ORR 21.8%). Adverse events between subgroups were similar to the overall study population, the most common being thrombocytopenia (29.1%), fatigue (7.5%), and nausea (6.0%). Conclusion: Regardless of prior therapy and disease refractory status, selinexor treatment demonstrated results consistent with its novel mechanism of action and lack of cross-resistance. Thus, single agent oral selinexor can induce deep, durable, and tolerable responses in patients with DLBCL who have recurrent disease after several chemoimmunotherapy combination regimens. (C) 2021 Published by Elsevier Inc.

Tisagenlecleucel (tisa‐cel) is a second‐generation autologous CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy approved for relapsed/refractory (R/R) large B‐cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa‐cel in the standard‐of‐care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa‐cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa‐cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non‐relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow‐up of 14.1 months from CAR T‐cell infusion, median progression‐free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa‐cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses., This article provides real‐world European data on the results of relapsed/refractory large B‐cell lymphoma patients treated with tisagenlecleucel.

Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p = 3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts.

Primary mediastinal large B-cell lymphoma (PMBCL) is a rare aggressive B-cell lymphoma characterized by the frequent presence of amplification and translocation events at 9p24.1, resulting in the expression of the programmed cell death-1 (PD-1) ligands PD-L1 and PD-L2. Pembrolizumab, a humanized anti-PD-1 monoclonal antibody, binds PD-1 and blocks this interaction, enhancing the activity of the immune system against tumor cells, and has shown activity in PMBCL and in some cases of primary and secondary central nervous system (CNS) lymphoma. We report the case of a 40-year-old woman diagnosed with relapsed PMBCL and secondary CNS involvement who responded to pembrolizumab monotherapy, allowing for a later allogeneic stem cell transplant.

Introduction The impact of an admission to ICU before stem cell transplantation (SCT) on post-SCT outcome is not well established. Patients and methods We reviewed the medical records of patients who had received a first SCT between 2000 and 2016 in our institution. The outcome of 22 patients who required ICU admission during chemotherapy prior to SCT (ICU group) was compared with 44 matched patients (1:2) who did not need it (NO-ICU group). Results There were no differences in transplant complications, in time to neutrophil and platelet recovery or in the length of hospital stay during SCT between the ICU and NO-ICU groups. However, microbiologically documented infections were more common in the ICU group (16/20) than in the NO-ICU group (18/39) (p = .027). The 5-yr overall survival probability (CI 95%) was 49% (28–70%) in the ICU vs. 45% (29–61%) in the NO-ICU group (p = .353), while the 5-yr incidence of non-relapse mortality was 32% (14–52%) and 24% (12–38%) (p = .333), respectively. Six patients (27%) in the ICU group and 8 (18%) in the NO-ICU group required admission to the ICU during or after the SCT procedure (p = .293). Twelve (54%) patients in the ICU and 22 (50%) in the NO-ICU group died, the causes of death were similar in both groups. Conclusion Our results show that admission to the ICU prior to SCT does not have a negative impact on patient outcomes following SCT and should not be considered as an exclusion criterion for SCT.

Current care for patients with follicular lymphoma (FL) offers most of them long-term survival. Improving it further will require careful patient selection. This review focuses on predictive biomarkers (ie, those whose outcome correlations depend on the treatment strategy) in FL, because awareness of what patient subsets benefit most or least from each therapy will help in this task. The first part of this review aims to summarize what biomarkers are predictive in FL, the magnitude of the effect and the quality of the evidence. We find predictive biomarkers in the setting of (a) indication of active treatment, (b) front-line induction (use of anthracyline-based regimens, CHOP vs bendamustine, addition of rituximab), (c) post-(front-line)induction (rituximab maintenance, radioimmunotherapy), and (d) relapse (hematopoietic stem cell transplant) and targeted agents. The second part of this review discusses the challenges of precision medicine in FL, including (a) cost, (b) clinical relevance considerations, and (c) difficulties over the broad implementation of biomarkers. We then provide our view on what biomarkers may become used in the next few years. We conclude by underscoring the importance of assessing the potential predictiveness of available biomarkers to improve patient care but also that there is a long road ahead before reaching their broad implementation due to remaining scientific, technological, and economic hurdles.

BACKGROUND: Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer with a median overall survival of less than 6 months. We aimed to assess the response to single-agent selinexor, an oral selective inhibitor of nuclear export, in patients with relapsed or refractory DLBCL who had no therapeutic options of potential clinical benefit. METHODS: SADAL was a multicentre, multinational, open-label, phase 2b study done in 59 sites in 19 countries. Patients aged 18 years or older with pathologically confirmed diffuse large B-cell lymphoma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received two to five lines of previous therapies, and progressed after or were not candidates for autologous stem-cell transplantation were enrolled. Germinal centre B-cell or non-germinal centre B-cell tumour subtype and double or triple expressor status were determined by immunohistochemistry and double or triple hit status was determined by cytogenetics. Patients received 60 mg selinexor orally on days 1 and 3 weekly until disease progression or unacceptable toxicity. The study was initially designed to evaluate both 60 mg and 100 mg twice-weekly doses of selinexor; however, the 100 mg dose was discontinued in the protocol (version 7.0) on March 29, 2017, when an improved therapeutic window was observed at 60 mg. Primary outcome was overall response rate. The primary outcome and safety were assessed in all patients who received 60 mg selinexor under protocol version 6.0, or enrolled under protocol versions 7.0 or higher and received at least one dose of selinexor. This trial is registered at ClinicalTrials.gov, NCT02227251 (active but not enrolling). FINDINGS: Between Oct 21, 2015, and Nov 2, 2019, 267 patients were randomly assigned, with 175 allocated to the 60 mg group and 92 to the discontinued 100 mg group. 48 patients assigned to the 60 mg group were excluded due to enrolment before version 6.0 of the protocol; the remaining 127 patients received selinexor 60 mg and were included in analyses of primary outcome and safety. The overall response rate was 28% (36/127; 95% CI 20·7-37·0); 15 (12%) achieved a complete response and 21 (17%) a partial response. The most common grade 3-4 adverse events were thrombocytopenia (n=58), neutropenia (n=31), anaemia (n=28), fatigue (n=14), hyponatraemia (n=10), and nausea (n=8). The most common serious adverse events were pyrexia (n=9), pneumonia (n=6), and sepsis (n=6). There were no deaths judged as related to treatment with selinexor. INTERPRETATION: Single-drug oral selinexor induced durable responses and had a manageable adverse events profile in patients with relapsed or refractory DLBCL who received at least two lines of previous chemoimmunotherapy. Selinexor could be considered a new oral, non-cytotoxic treatment option in this setting. FUNDING: Karyopharm Therapeutics Inc.

There is no standard treatment for relapsed follicular lymphoma (FL). Although platinum-based combinations are one of the most used treatments, few data have been reported in this setting. Our aim was to analyse R-ESHAP efficacy in relapsed FL patients. We retrospectively analysed 80 FL patients treated with R-ESHAP in the first or successive relapses. Responding patients received a stem cell transplantation following R-ESHAP. Seventeen histologically transformed patients were included. Median age was 50 years. At R-ESHAP initiation, 85% of the patients were in an advanced stage, 28% had a bulky disease and 40% had increased LDH. There were no statistically significant differences between POD24 and non-POD24 patients in terms of response to R-ESHAP (ORR 72% vs. 93%, p = 0.109). When analyzing R-ESHAP efficacy according to the response to the immediately previous line, patients achieving CR or PR had better CR rates to R-ESHAP than those who did not respond (CR of 57% vs. 15%, respectively, p = 0.009), as well as differences in OS (7.2 vs. 1.4 years, p < 0.0001) and in PFS (2.1 vs. 0.3 years, p < 0.0001). R-ESHAP is an effective treatment in relapsed FL patients who respond to the previous line and has to be considered as an adequate alternative for some 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.

Key Points Patients with FL anti-HBc+ present with worse 10-year PFS and OS.Patients with anti-HBc+ present with a higher frequency of ARID1A mutations and lack of EP300 mutations., Epidemiological studies have demonstrated the association between hepatitis B virus (HBV) infection and B-cell non–Hodgkin lymphoma (NHL), mainly for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). We studied a cohort of 121 patients with FL for HBV infection status, clinical features, and gene mutational profile. Anti-HBc was detectable in 16 patients (13.2%), although all had undetectable HBV DNA. Anti-HBcore+ (anti-HBc+) cases presented with older age at diagnosis than anti-HBc− cases (68.1 vs 57.2 years; P = .007) and higher β2-microglobulin (56.3% vs 28.9%; P = .04). All patients included in the study fulfilled criteria for treatment and received therapy with rituximab or rituximab-containing chemotherapy. There were no episodes of HBV reactivation or HBV hepatitis during treatment and/or maintenance. Remarkably, anti-HBc+ patients had significantly lower 10-year progression-free survival (PFS; 12.9% vs 58.3%; P < .0001) and overall survival (OS; 22.0% vs 86.2%; P < .0001), that remained at multivariate analysis. Gene mutational profiling of all cases showed that anti-HBc+ cases had higher incidence of ARID1A mutations and absence of EP300 mutations, 2 key epigenetic regulators in FL. Overall, our study shows that FL patients with resolved HBV infection have a worse outcome independently of other well-known clinical risk factors and a distinct gene mutational profile.

The phase 2b, open-label, multicenter SADAL study evaluated single agent oral selinexor, a selective inhibitor of nuclear export (SINE) compound, in patients with diffuse large B cell lymphoma (DLBCL) after >= 2 lines of systemic therapy. Similar activity was observed in GCB- and non-GCB DLBCL with a trend to higher response rates in DLBCL transformed from follicular lymphoma. Lower response rates were observed in double expressor DLBCL; higher response rates were observed in patients with baseline hemoglobin >= 10 g/dL and normal levels of C-MYC or BCL-2 expression (51%). Overall, strong single agent activity with selinexor were observed in patients with relapsed/refractory DLBCL.Background: The SADAL study evaluated oral selinexor in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior lines of systemic therapy. In this post-hoc analysis, we analyzed the outcomes of the SADAL study by DLBCL subtype to determine the effects of DLBCL subtypes on efficacy and tolerability of selinexor. Patients and Methods: Data from 134 patients in SADAL were analyzed by DLBCL subtypes for overall response rate (ORR), overall survival (OS), duration of treatment response, progression-free survival, and adverse events rate. Results: ORR in the entire cohort was 29.1%, and similar in patients with germinal center (GCB) versus non-GCB DLBCL (31.7% vs. 24.2%, P = 0.45); transformed DLBCL showed a trend towards higher ORR than de novo DLBCL: 38.7% vs. 26.2% (P = 0.23). Despite similar prior treatment regimens and baseline characteristics, patients with DLBCL and normal C-MYC/BCL-2 protein expression levels had a significantly higher ORR (46.2% vs.14.8%, P = 0.012) and significantly longer OS (medians 13.7 vs. 5.1 months, hazard ratio 0.43 [95% CI, 0.23-0.77], P = 0.004) as compared with those whose DLBCL had C-MYC and BCL-2 overexpression. Among patients who had normal expression levels of either C-MYC or BCL-2 and baseline hemoglobin levels >= 10g/dL, ORR was 51.5% (n = 47), with median OS of 15.5 months and median PFS of 4.6 months. Similar rates of adverse events were noted in all subgroups. Conclusions: Overall, single agent oral selinexor showed strong responses in patients with limited treatment alternatives regardless of germinal center B-cell type or disease origin. (C) 2021 Elsevier Inc. All rights reserved.

Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) cases have a poor outcome. Here we analysed clinico-biological features in 373 DLBCL patients homogeneously treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP), in order to identify variables associated with early failure to treatment (EF), defined as primary refractoriness or relapse within 12 months from diagnosis. In addition to clinical features, mutational status of 106 genes was studied by targeted next-generation sequencing in 111 cases, copy number alterations in 87, and gene expression profile (GEP) in 39. Ninety-seven cases (26%) were identified as EF and showed significantly shorter overall survival (OS). Patients with B symptoms, advanced stage, high levels of serum lactate dehydrogenase (LDH) or beta 2-microglobulin, low lymphocyte/monocyte ratio and higher Revised International Prognostic Index (R-IPI) scores, as well as those with BCL2 rearrangements more frequently showed EF, with R-IPI being the most important in logistic regression. Mutations in NOTCH2, gains in 5p15 center dot 33 (TERT), 12q13 (CDK2), 12q14 center dot 1 (CDK4) and 12q15 (MDM2) showed predictive importance for EF independently from R-IPI. GEP studies showed that EF cases were significantly enriched in sets related to cell cycle regulation and inflammatory response, while cases in response showed over-representation of gene sets related to extra-cellular matrix and tumour microenvironment.

The frequency of aggressive subtypes of B-cell non-Hodgkin lymphoma (B-NHL), such as high-grade B-cell lymphomas (HGBL) with MYC and BCL2 and/or BCL6 rearrangement (HGBL-DH/TH) or Burkitt-like lymphoma (BL) with 11q aberration, is not well known in the HIV setting. We aimed to characterise HIV-associated aggressive B-NHL according to the 2017 WHO criteria, and to identify genotypic and phenotypic features with prognostic impact. Seventy-five HIV-associated aggressive B-NHL were studied by immunohistochemistry (CD10, BCL2, BCL6, MUM1, MYC, and CD30), EBV-encoded RNAs (EBERs), and fluorescence in situ hybridisation (FISH) to evaluate the status of the MYC, BCL2, and BCL6 genes and chromosome 11q. The 2017 WHO classification criteria and the Hans algorithm, for the cell-of-origin classification of diffuse large B-cell lymphomas (DLBCL), were applied. In DLBCL cases, the frequencies of MYC and BCL6 rearrangements (14.9 and 27.7%, respectively) were similar to those described in HIV-negative patients, but BCL2 rearrangements were infrequent (4.3%). MYC expression was identified in 23.4% of DLBCL cases, and coexpression of MYC and BCL2 in 13.0%, which was associated with a worse prognosis. As for BL cases, the expression of MUM1 (30.4%) conferred a worse prognosis. Finally, the prevalence of HGBL-DH/TH and BL-like with 11q aberration are reported in the HIV setting. The phenotypic and genotypic characteristics of HIV-associated aggressive B-NHL are similar to those of the general population, except for the low frequency of BCL2 rearrangements in DLBCL. MYC and BCL2 coexpression in DLBCL, and MUM-1 expression in BL, have a negative prognostic impact on HIV-infected individuals.

This is a randomized phase-2 trial aimed to compare consolidation vs. maintenance in untreated patients with follicular lymphoma (FL) responding to induction. 146 patients were enrolled from 25 Spanish institutions (ZAR2007; ClinicalTrials.gov #NCT00662948). Patients in PR or CR/CR[u] after R-CHOP were randomized 1:1 to