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Background: There are few reports of clinical practice treatment patterns and efficacy in mantle cell lymphoma (MCL). Materials and Methods: We retrospectively studied a large, multicenter, cohort of patients with MCL diagnosed between 2000 and 2020 in eight institutions. Results: 536 patients were registered (73% male, median of 70 years). Front‐line treatment was based on high‐dose cytarabine, bendamustine, and anthracyclines in 42%, 12%, and 15%, respectively. The median PFS for all patients was 45 months; 68, 34, and 30 months for those who received high‐dose cytarabine‐based, bendamustine‐based and anthracycline‐based therapy. 204 patients received second‐line. Bendamustine‐based treatment was the most common second‐line regimen (36% of patients). The median second‐line PFS (sPFS) for the entire cohort was 14 months; 19, 24, and 31 for bendamustine‐, platinum‐, and high‐dose cytarabine‐based regimens, with broad confidence intervals for these latter estimates. Patients treated with cytarabine‐based therapies in the front‐line and those with front‐line PFS longer than 24 months had a substantially superior sPFS. Conclusion: Front‐line treatment in this cohort of MCL was as expected and with a median PFS of over 3.5 years. Second‐line treatment strategies were heterogeneous and the median second‐line PFS was little over 1 year. [ABSTRACT FROM AUTHOR]

Parsaclisib, a potent and highly selective phosphoinositide 3-kinase δ inhibitor, has shown clinical activity in relapsed/refractory (R/R) B-cell lymphoma. The phase 1 CITADEL-112 (NCT03424122) study assessed safety and efficacy of parsaclisib in combination with investigator choice standard of care (SOC; rituximab [Treatment A], rituximab plus bendamustine [Treatment B], or ibrutinib [Treatment C]) in 50 patients with R/R B-cell lymphoma. The most common treatment-emergent adverse events included neutropenia (62.5%, 50.0%, and 50.0% of patients in Treatments A, B, and C, respectively); diarrhea (37.5%) and anemia (31.3%) in Treatment A; abdominal pain, asthenia, diarrhea, and nausea (each 33.3%) in Treatment B; and increased alanine and aspartate aminotransferase (each 37.5%) in Treatment C. Objective responses were observed in 13 patients (81.3%) in Treatment A, 10 (55.6%) in Treatment B, and 8 (50.0%) in Treatment C. Parsaclisib combined with SOC therapies had an expected safety profile and promising efficacy in patients with R/R B-cell lymphomas. [ABSTRACT FROM AUTHOR]

Introduction: Mantle cell lymphoma (MCL) is an incurable disease with an aggressive clinical course, and most patients eventually relapse after chemotherapy. Targeted therapies developed for relapsed/refractory MCL have been approved based on clinical trial data. However, real-world setting data are scarce and scattered. Areas Covered: This systematic review aimed to collect, synthesize, and describe the characteristics and treatment outcomes of patients with relapsed/refractory MCL after receiving a second or subsequent line of therapy in the real-world setting. Expert Opinion: R/R MCL is clinically and biologically heterogeneous and still represents a therapeutic challenge, with high-risk and early relapsed patients remaining an unmet medical need. This systematic review is limited by the quality of the available data and the difficulty of comparing outcomes in R/R MCL due to the heterogeneity of the disease, but the results suggest that covalent BTKis should be positioned as second-line therapy, followed by CAR T-cells in BTK-i-relapsed patients. Chemo-free and combination therapies with established chemoimmunotherapy backbones in the relapsed and front-line settings have been recently developed, and front-line options are being improved to move targeted and cellular therapies to earlier lines, including front-line therapy, in elderly and younger fit patients. In the upcoming years, many new targeted agents will play an important role and will be incorporated to the routine practice as their sequence, and outcomes in unselected patients are determined. [ABSTRACT FROM AUTHOR]

The SCHOLAR-2 retrospective study highlighted poor overall survival (OS) with standard of care (SOC) regimens among patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) who failed a covalent Bruton tyrosine kinase inhibitor (BTKi). In the ZUMA-2 single-arm trial, brexucabtagene autoleucel (brexu-cel; autologous anti-CD19 CAR T-cell therapy) demonstrated high rates of durable responses in patients with R/R MCL who had previous BTKi exposure. Here, we compared OS in ZUMA-2 and SCHOLAR-2 using three different methods which adjusted for imbalances in prognostic factors between populations: inverse probability weighting (IPW), regression adjustment (RA), and doubly robust (DR). Brexu-cel was associated with improved OS compared to SOC across all unadjusted and adjusted comparisons. Hazard ratios (95% confidence intervals) were 0.38 (0.23, 0.61) for IPW, 0.45 (0.28, 0.74) for RA, and 0.37 (0.23, 0.59) for DR. These results suggest a substantial survival benefit with brexu-cel versus SOC in patients with R/R MCL after BTKi exposure. [ABSTRACT FROM AUTHOR]

Parsaclisib is a potent and highly selective PI3Kδ inhibitor that has shown clinical benefit with monotherapy in a phase 2 study in relapsed or refractory (R/R) follicular lymphoma (FL). CITADEL‐102 (NCT03039114), a phase 1, multicenter study, assessed the efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with R/R FL. Patients were ≥18 years of age with histologically confirmed and documented CD20‐positive FL, and R/R to previous rituximab‐containing treatment regimens. Part one (safety run‐in) determined the maximum tolerated dose of parsaclisib in combination with standard dosage regimens of obinutuzumab and bendamustine. Part two (dose expansion) was an open‐label, single‐group design evaluating safety, tolerability (primary endpoint), and efficacy (secondary endpoint) of parsaclisib combination therapy. Twenty‐six patients were enrolled in CITADEL‐102 and all patients received parsaclisib 20 mg once daily for 8 weeks, followed by 20 mg once weekly thereafter, in combination with obinutuzumab and bendamustine. One patient in safety run‐in experienced a dose‐limiting toxicity of grade 4 QT interval prolongation that was considered related to parsaclisib. Eight patients (30.8%) discontinued treatment due to treatment‐emergent adverse events (TEAEs) of colitis (2 [7.7%]), alanine aminotransferase and aspartate aminotransferase increase (both in one patient [3.8%]), neutropenia, thrombocytopenia, QT prolongation, tonsil cancer, and maculopapular rash (each 1 [3.8%]). The most common reported TEAEs were pyrexia (53.8%), neutropenia (50.0%), and diarrhea (46.2%). Twenty‐three patients (88.5%) experienced grade 3 or 4 TEAEs; the most common were neutropenia (34.6%), febrile neutropenia (23.1%), and thrombocytopenia (19.2%). Seventeen patients (65.4%) had a complete response and 3 patients (11.5%) had a partial response, for an objective response rate of 76.9%. Overall, results from CITADEL‐102 suggest that the combination of parsaclisib with obinutuzumab and bendamustine did not result in unexpected safety events, with little evidence of synergistic toxicity, and demonstrated preliminary efficacy in patients with R/R FL who progressed following prior rituximab‐containing regimens. [ABSTRACT FROM AUTHOR]

PURPOSE: Although follicular lymphoma is characterized by long natural history and frequent relapses, data on the number of patients receiving subsequent therapy lines are scarce. To perform reliable health economical calculations for various treatment options, data regarding the lifetime number of therapy courses are needed. The purpose of this study was to use real-world data to create a model that could estimate the treatment burden over a 20-year period. MATERIALS AND METHODS: We performed a 20-year simulation on the basis of retrospectively obtained multicenter data of 743 patients with follicular lymphoma. The simulation was carried out in two steps: First, a competing risk model on the basis of Weibull distribution was used to simulate the state transitions from diagnosis onward and from first-line therapy onward. Then, the data were completed by imputing on the basis of the existing data. Completion of data was repeated for 1,000 times to estimate reliability. RESULTS: In 20 years, 97% (2.5-97.5 percentile range: 96%-98%), 66% (61%-70%), 34% (30%-41%), and 15% (9%-18%) of the patients received first-line, second-line, third-line, and fourth-line therapies, respectively. The median number of therapy lines received by each patient was two. CONCLUSION: Despite long remissions, approximately two thirds of the patients receive at least two lines and one-third at least three lines of therapy during their lifetime. [ABSTRACT FROM AUTHOR]

Summary: The aims of our study were to analyse compliance with the 2014 GELTAMO SMZL Guidelines, in patients with splenic marginal zone lymphoma (SMZL), and to evaluate the outcome according to the HPLLs/ABC‐adapted therapeutic strategy. Observational prospective multicenter study of 181 SMZL patients diagnosed between 2014 and 2020. Lymphoma‐specific survival (LSS), composite event‐free survival (CEFS) and response rates were assessed. 57% of the 168 patients included in the analysis followed the Guidelines. The overall response rate was higher in the rituximab chemotherapy and in the rituximab arms compared with the splenectomy arm (p < 0.001). The 5‐year overall survival was 77% and the 5‐year LSS of 93%. There were no differences in the 5‐year LSS according to the treatment received (p = 0.68). The 5‐year CEFS in the overall series was 45%, and there were significant differences between scores A and B (p = 0.036). There were no significant differences when comparing LSS and progression‐free survival in patients treated with rituximab or rituximab chemotherapy at diagnosis or after observation. Our data support HPLLs/ABC score as a practical tool for the management of SMZL, observation as the best approach for patients in group A and rituximab as the best treatment for group B. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Key Clinical Message: HHV8‐ and EBV‐negative primary effusion lymphoma is an extremely rare neoplasm involving body cavities without detectable tumor mass. It usually presents in elderly patients without known immunodeficiency. Compared to primary effusion lymphoma, it has a better prognosis. 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. [ABSTRACT FROM AUTHOR]

Aim: To design and implement a plan to improve oncohaematological patients' sleep. Background: The hospital environment can compromise inpatients' sleep, negatively impacting on health outcomes and patient satisfaction. Design and Method: 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. Results: 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. Conclusions: 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. Relevance to clinical practice: 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. [ABSTRACT FROM AUTHOR]

Summary: Mantle cell lymphoma (MCL) is a rare peripheral B‐cell lymphoma characterised by eventual relapse and progression towards a more aggressive disease biology. With the introduction of rituximab‐ and cytarabine‐based immunochemotherapy regimens, the prognosis of the disease has changed dramatically over the last two decades. To assess the real‐world survival of patients with MCL, we used a population‐based cohort of 564 patients with MCL who were diagnosed and treated between 2000 and 2020. Patient data were collected from seven Finnish treatment centres and one Spanish treatment centre. For the entire patient population, we report a 2‐year overall survival (OS) rate of 77%, a 5‐year OS of 58%, and a 10‐year OS of 32%. The estimated median OS was 80 months after diagnosis. MCL is associated with increased mortality across the entire patient population. Additionally, we assessed the survival of patients after MCL relapse with the aim of establishing a cut‐off point of prognostic significance. Based on our statistical analysis of survival after the first relapse, disease progression within 24 months of the initial diagnosis should be considered as a strong indicator of poor prognosis. [ABSTRACT FROM AUTHOR]

Summary: 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) (p < 0.001) 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. [ABSTRACT FROM AUTHOR]

Keywords: follicular lymphoma; mortality; cause of death; event-free survival; progression of disease; POD24 EN follicular lymphoma mortality cause of death event-free survival progression of disease POD24 458 462 5 10/25/22 20221101 NES 221101 Although the life expectancy of patients with follicular lymphoma (FL) has improved considerably over the last 20 years,1-4 ~20% of patients still experience progression of disease within 24 months (POD24) of first-line therapy.5,6 This early progression is an established independent risk factor for poor survival.5-8 In addition, recent studies reported that complete remission (CR) at 24 months after diagnosis or 30 months after induction therapy predicts a similar life expectancy to that of the general population.9,10 This study aimed to evaluate the links between disease status at 24 months, mortality and causes of death in patients with FL. Within the 24 months of treatment, 174 patients (17.6%) experienced progression (POD24 patients), while 630 patients (63.6%) did not. However, Sarkozy et al.14 reported contrary findings suggesting that subsequent cumulative incidences of lymphoma-related and non-lymphoma-related mortality were similar amongst patients who were event-free at 24 months. In contrast, POD24 patients are at risk of early death due to progressive lymphoma, which justifies more aggressive therapies coupled with higher treatment-related mortality and morbidity and increased societal cost. [Extracted from the article]

The ubiquitous, early‐stage expression, efficient internalization, limited off‐target effects, and high disease specificity of CD19 make it an attractive therapeutic target. Currently available anti‐CD19 therapies have demonstrated particular promise in patients with relapsed or refractory B‐cell non‐Hodgkin lymphoma. Selection of the most appropriate treatment strategy should be based on individual patient characteristics and the goal of therapy. However, evidence and knowledge about the sequencing of anti‐CD19 therapies are limited. Here, we review the current evidence for CD19 as a target in diffuse large B‐cell lymphoma and consider approaches to the use of anti‐CD19 therapy. [ABSTRACT FROM AUTHOR]

Real-world evidence comparing the efficacy of chimeric antigen receptor (CAR) T-cell therapy against that of the previous standard of care (SOC) for refractory large B-cell lymphoma (LBCL) is scarce. We retrospectively collected data from patients with LBCL according to SCHOLAR-1 criteria treated with commercial CAR T-cell therapy in Spain (204 patients included and 192 treated, 101 with axicabtagene ciloleucel [axi-cel], and 91 with tisagenlecleucel [tisa-cel]) and compared the results with a historical refractory population of patients (n = 81) obtained from the GELTAMO-IPI study. We observed superior efficacy for CAR-T therapy (for both axi-cel and tisa-cel) over pSOC, with longer progression-free survival (PFS) (median of 5.6 vs. 4–6 months, p ≤ 0.001) and overall survival (OS) (median of 15 vs. 8 months, p < 0.001), independently of other prognostic factors (HR: 0.59 (95% CI: 0.44–0.80); p < 0.001] for PFS, and 0.45 [(95% CI: 0.31–0.64)] for OS). Within the CAR-T cohort, axi-cel showed longer PFS (median of 7.3 versus 2.8 months, respectively, p = 0.027) and OS (58% versus 42% at 12 months, respectively, p = 0.048) than tisa-cel. These differences were maintained in the multivariable analysis. On the other hand, axi-cel was independently associated with a higher risk of severe cytokine release syndrome and neurotoxicity. Our results suggest that the efficacy of CAR-T cell therapy is superior to pSOC in the real-world setting. Furthermore, axi-cel could be superior in efficacy to tisa-cel, although more toxic, in this group of refractory patients according to SCHOLAR-1 criteria. [ABSTRACT FROM AUTHOR]

Background: The life expectancy of patients with follicular lymphoma (FL) has improved considerably since the introduction of rituximab. This study examined the proportion of deaths from progressive lymphoma and the impact of FL on survival compared with that in the general population. Methods: Altogether, 749 patients with grades 1 and 2 FL in 9 institutions between 1997 and 2016 were enrolled. Competing risk models were used to estimate the cumulative incidences of deaths from progressive lymphoma and from other reasons. Excess mortality was analyzed with respect to the corresponding background populations standardized for age and sex using the excess mortality model based on the penalized spline approach. Results: The median follow‐up duration was 69 months (range, 0‐226 months). The estimated 10‐year overall, disease‐specific, and net survival rates were 72.4%, 86.6%, and 86.4%, respectively. The cumulative incidence of deaths from progressive lymphoma was slightly smaller than that of other causes in the study population (estimated 10‐year cumulative incidences: 12.3% [95% CI, 9.6%‐15.3%] and 15.4% [95% CI, 12.2%‐18.8%], respectively). Excess mortality was observed for up to 10 years after diagnosis, and it slightly increased with time. Conclusions: Deaths from progressive lymphoma are nearly as common as deaths from other causes in FL patients during the rituximab era. Despite the improvements in survival, there was evidence of excess mortality resulting from FL for at least 10 years after diagnosis. Deaths from progressive lymphoma are nearly as common as those from other reasons in patients with follicular lymphoma (FL) in the rituximab era. Despite the improvements in survival, there is evidence of excess mortality from FL for at least 10 years after diagnosis. [ABSTRACT FROM AUTHOR]

Intraocular involvement in patients with primary central-nervous-system lymphoma (oPCNSL) usually affects the retina, vitreous or optic nerve and can occur in isolation or, more commonly, in association with brain lymphoma.1,2 It has been estimated that 10%-25% of patients with PCNSL have ocular dissemination at diagnosis.3 For these reasons, an ophthalmic examination at diagnosis is highly recommended. In five out of the 26 (19%) patients, ocular symptoms, usually described as a decrease in visual acuity, preceded the CNS symptoms. In the oPCNSL group, diagnosis of PCNSL was done by vitrectomy (three patients) or brain biopsy (23 patients). [Extracted from the article]