The R2 (lenalidomide-rituximab) and R2 with bendamustine (R2B) regimens are both feasible in relapsed/refractory follicular lymphoma (R/R FL), but prospective phase II data on R2B are lacking. In this multinational, prospective, randomised, non-comparative trial, patients with R/R FL were randomised 1:1 to R2 (arm A) or R2B (arm B). Patients achieving CT-based partial or complete remission (PR/CR) received rituximab maintenance every 3 months for 2 years. Co-primary endpoints were investigator-assessed CR rates at end-of-induction (EOI) and severe toxicity rates. Between December 2014 and July 2019, 92 patients were randomized. The trial was stopped prematurely due to slow accrual. CR rates at EOI were 11.4% (95% CI [3.8, 24.6%]) for R2 and 15.2% (CI [6.3, 28.9%]) for R2B. With a median follow-up of 74 months, predefined severe toxicities occurred in 3 (6.8%; CI [1.4, 18.7%]) and 6 pts (13.0%, CI [4.9, 26.3%]) in Arm A and Arm B respectively, with 2 pneumonia-related deaths in arm A and no treatment-related deaths in arm B; 43% and 66% experienced any grade 3-4 AE (2%/7% grade 4). At 60 months, in arms A and B event free survival (EFS) was 39.5% (CI [25.1, 53.6%]) and 56.4% (CI [40.1, 69.3%]). Overall survival (OS) was excellent at 72.1% and 86.3%, respectively. R2 and R2B are both effective treatment regimens for R/R FL. While CT-based CR rates were low, treatment with R2B resulted in numerically longer median EFS and OS, but this was associated with higher toxicity.

BACKGROUND:T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive mature T-cell malignancy with limited therapeutic options. Alemtuzumab remains the backbone of therapy, and fit responders are consolidated with allogeneic stem cell transplantation (alloSCT). However, contemporary population-level outcomes remain poorly defined. METHODS:All T-PLL cases diagnosed between 2001 and 2023 were identified from the nationwide Netherlands Cancer Registry. Overall survival (OS) and survival after relapse (OS2) were analyzed in 220 patients. Detailed treatment-line data were available for patients diagnosed from 2014 onward (n = 120), enabling assessment of treatment sequencing, response, and progression-free survival (PFS). RESULTS:Median age at diagnosis was 71 years; 56% were male. Overall, 54% received systemic therapy, of whom 25% underwent transplantation. Median OS was 13.5 months; 2- and 5-year OS were 36% and 10%, with no improvement over time. Alemtuzumab was the predominant frontline therapy and was associated with higher response and survival than other regimens. Consolidation with alloSCT provided the greatest likelihood of durable disease control, although only one-third of treated patients were eligible. Survival after relapse remained poor (median OS2, 5-7 months), and later treatment lines rarely produced durable benefit. Nearly half of patients were initially managed with observation; long-term survival remained limited after progression. CONCLUSIONS:Alemtuzumab followed by alloSCT remains the most effective strategy for fit patients with T-PLL, yet long-term survival is uncommon and has not improved over two decades. High relapse rates and poor salvage outcomes underscore the need for novel targeted and immune-based approaches and optimized post-remission strategies.

Primary central nervous system lymphoma (PCNSL) is a rare aggressive B-cell non-Hodgkin lymphoma confined to the central nervous system, without systemic involvement. The incidence has increased over the past 3 decades. The prognosis has improved in patients up to 70 years old, and this type of lymphoma can be potentially cured. The gold standard of diagnosing PCNSL is histological, usually on a brain biopsy specimen via a neurosurgical procedure. Recent developments in both imaging and laboratory analyses of the cerebrospinal fluid, can be helpful in narrowing the differential diagnosis, diagnosing PCNSL itself, and in follow-up after treatment. This narrative review gives an overview of the epidemiology, diagnosis, and treatment of PCNSL, with an emphasis on recent developments in diagnostic techniques and treatment.

Background Emerging BTK inhibitor (BTKi)-resistance mutations and the scaffolding function of BTK present a need for approaches beyond BTKi for treating B-cell malignancies. NX-5948 is a novel, orally administered, small molecule that induces specific degradation of wild-type and mutant forms of BTK in B-cells by the cereblon E3 ligase complex. NX-5948 can cross the blood-brain barrier. Methods NX-5948-301 is a Phase 1, first-in-human dose-escalation trial evaluating the safety, tolerability, and clinical activity of NX-5948 in patients with relapsed/refractory CLL and NHL/WM. Key eligibility criteria: ≥2 prior therapy lines; measurable or other evaluable disease per indication-specific response criteria; ECOG PS 0–1. Primary objective: evaluate safety and tolerability of NX-5948 and establish maximum tolerated dose and recommended Phase 2 dose. Key secondary objectives: characterize PK/PD profile and assess preliminary efficacy of NX-5948. Results As of 17 April 2024, 79 patients (31 CLL, 48 NHL/WM) were enrolled at 6 daily oral dose levels: 50 mg (n=7), 100 mg (n=8), 200 mg (n=14), 300 mg (n=17), 450 mg (n=17), 600 mg (n=16). Median age: 67 (range 35–88) years; males: 65.8%; median prior lines of therapy: 4 (range 2–14), including for CLL: prior BTKi and BCL2i (87.1%). Baseline mutations in CLL were frequent: TP53, (46.7%), BTK (43.3%), PLCG2 (20.0%). NX-5948 was well tolerated across all doses with one treatment-related SAE and two discontinuations due to TEAEs. The most common TEAEs were purpura/contusion (35.4%, no Grade ≥3), thrombocytopenia (26.6%, 8.9% Grade ≥3), neutropenia (20.3%, 15.2% Grade ≥3). No new atrial fibrillation/flutter was reported. Rapid, robust, and sustained BTK degradation was observed in all patients regardless of absolute BTK starting level, tumor type or dose. Among 26 disease-evaluable patients with CLL, 18 clinical responses (PR/PR-L) were observed across all dose levels (ORR 69.2%). Summary/Conclusion Findings demonstrate a tolerable safety profile of NX-5948 across B-cell malignancies. Deep clinical responses were observed in a heavily pre-treated population of patients with CLL, some with BTKi resistance mutations and high-risk molecular features. These data warrant continued investigation of NX-5948 in patients with CLL.

Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma (NHL) manifesting in the brain, spinal cord, cerebrospinal fluid and/or eyes, in the absence of systemic manifestations. With an increasing incidence and a 30% 5-year overall survival if promptly treated, timely diagnosis and subsequent treatment is paramount. The typical MRI appearance for PCNSL is a solitary or multiple T2-hypointense, homogeneous gadolinium-enhancing lesion with restricted diffusion. Dexamethasone treatment might compromise and delay the diagnosis. Hallmark of treatment is induction with intravenous high-dose methotrexate consisting polychemotherapy followed by consolidation treatment. Consolidation treatment consists of either whole brain radiotherapy (WBRT) or autologous stem cell transplantation (ASCT). Given the (cognitive) side effects of WBRT, ASCT is increasingly being used as the first choice of treatment.

Primary central nervous system lymphoma (PCNSL) is generally characterized by a poor prognosis and frequent relapsing disease. Consolidation therapy in the upfront setting usually consists of an autologous stem cell transplantation. We report the case of a 19-year old Caucasian male who had previously undergone an allogeneic stem cell transplantation with complete engraftment for the treatment of juvenile myelomonocytic leukaemia when he was one year old. He presented with two episodes of (donor-derived) PCNSL from allogeneic stem cells, however after induction chemotherapy he failed to harvest stem cells for the consolidation with autologous stem cell transplantation. He was consolidated successfully with a second allogeneic stem cell transplantation with another donor after conditioning with thiotepa, busulfan and fludarabine.

Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m2/cycle) were included. The regimens included MATRIX (HD-MTX, HD-AraC, thiotepa, and rituximab), (R)MBVP±HD-AraC (HD-MTX, teniposide/etoposide, carmustine, prednisolone, ± HD-AraC, ± rituximab), (R)MP (HD-MTX, procarbazine, ± rituximab), and a combination of HD-MTX and HD-AraC. The overall response rate after induction was 69 %, 28 % complete remission and progressive disease was observed in 100 (29 %) patients. 126 (36 %) patients received consolidation, including high-dose-BCNU-thiotepa with autologous stem cell transplantation (HD-BCNU-TT/ASCT, n = 59 (17 %)) or whole brain radiotherapy (WBRT, n = 67 (19 %)). Clinical characteristics associated with adverse mortality risk by multivariable prognostication contained age > 60 years (HR 1.61, p = 0.011), elevated LDH (HR 1.75, p = 0.004) and WHO status ≥ 2 (HR 1.56, p = 0.010). Independently, induction regimens containing HD-AraC demonstrated survival benefit compared to induction regimens without HD-AraC (HR 0.59, p = 0.002). Without preference for HD-BCNU-TT/ASCT or WBRT, a favorable effect of consolidation (HR 0.44 and HR 0.42, p < 0.001) was confirmed, also with consolidation as time-dependent variable. Competing risk analysis showed similar low incidence of lymphoma-unrelated deaths in consolidated and unconsolidated patients. This study confirms that age, elevated LDH and WHO status increase the mortality risk. HD-AraC containing treatment regimens and consolidation with HD-BCU-TT/ASCT or WBRT were associated with superior survival, including a favorable low incidence of lymphoma-unrelated deaths.

Chronic lymphocytic leukemia (CLL) manifests heterogeneously with varying outcomes. This population-based study examined causes of death (CODs), as registered by the physician who established the death, among 20,588 CLL patients diagnosed in the Netherlands between 1996 and 2020. Utilizing cause-specific flexible parametric survival models, we estimated cause-specific hazard ratios (HRs) and cumulative incidences of death due to CLL, solid malignancies, other hematological malignancies, infections, and other causes. Our findings reveal CLL as the predominant COD, contributing to around 40% of relative mortality, with a declining 5-year death probability from 16.8% in 1996-2002 to 7.6% in 2010-2020. Also, deaths attributed to solid malignancies, other hematological malignancies, and other COD diminished over time, as evidenced by respective HRs (95% confidence interval) of 0.68 (0.60%-0.77%), 0.45 (0.38%-0.53%), and 0.77 (0.66%-0.90%). In summary, our comprehensive, population-based analysis underscores a noticeable reduction in CLL-attributed deaths and other competing causes over the studied period. Nonetheless, CLL is registered as the most prevalent cause of mortality among contemporary diagnosed patients with CLL, emphasizing the continued relevance of CLL-centric clinical strategies and research.

High-dose methotrexate (HD-MTX)-based polychemotherapy is widely used for patients with central nervous system (CNS) lymphoma. The pharmacokinetic (PK) variability and unpredictable occurrence of toxicity remain major concerns in HD-MTX treatment. This study aimed to characterize the population PK of HD-MTX in patients with CNS lymphoma and to identify baseline predictors and exposure thresholds that predict a high risk of nephro- and hepatotoxicity. Routinely monitored serum MTX concentrations after intravenous infusion of HD-MTX and MTX dosing information were collected retrospectively. Acute event of toxicity (≥ grade 1) was defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 on the basis of serum creatinine and alanine aminotransferase. A population PK model was developed in NONMEM. Toxicity data were analyzed using a logistic regression model, and potential baseline and exposure-related predictors were investigated. In total, 1584 MTX concentrations from 110 patients were available for analysis. A two-compartment population PK model adequately described the data. Estimated glomerular filtration rate (eGFR), treatment regimen, albumin, alkaline phosphatase, and body weight were identified as significant covariates that explain the PK variability of HD-MTX. Baseline eGFR and sex were identified as significant predictors for renal toxicity, and MTX dose (mg/m2) was the strongest predictor for hepatotoxicity. The MTX area under the concentration–time curve (AUC24–∞) and concentration at 24 h (C24h) were shown to correlate with renal toxicity only, and 49,800 μg/L × h (109.6 μmol/L × h) and C24h > 3930 μg/L (8.65 μmol/L) were potential exposure thresholds predicting high risk (proportion > 60

On behalf of the European MCL Network, ML and EH contributed equally Introduction: In younger patients with mantle cell lymphoma (MCL), the addition of ibrutinib during induction immuno-chemotherapy and as 2-years maintenance with and without autologous stem cell transplantation (ASCT) has shown high efficacy in the 3-arm randomized TRIANGLE trial (Dreyling et al., Lancet 2024), establishing a new standard of care induction treatment and maintenance. However, the efficacy comparison of the two ibrutinib-containing treatment arms with and without ASCT was still ongoing. With prolonged follow-up, we now aim to clarify the role of ASCT in the context of ibrutinib-containing treatment, to confirm the previously observed treatment effects and to perform overall survival (OS) comparisons. Patients and methods: In 2016, the European MCL Network initiated the randomized, open-label, 3-arm TRIANGLE trial to evaluate the addition of ibrutinib to standard treatment with ASCT (arm A+I) in comparison to the previous standard treatment (arm A) and an ibrutinib-containing treatment without ASCT (arm I). Patients with previously untreated, advanced stage II-IV MCL, up to 65 years, and suitable for high-dose cytarabine and ASCT, were randomized 1:1:1 to the 3 trial arms in 13 European countries and Israel. Study treatment consisted of 6 alternating cycles of R-CHOP and R-DHAP without (arm A) or with ibrutinib added to R-CHOP cycles and as 2 years maintenance (arms A+I, I). ASCT was planned for patients of arms A and A+I responding to induction therapy. Rituximab maintenance was recommended to be applied according to national guidelines in responding patients of each trial arm. For the primary outcome, failure-free survival (FFS), stable disease at the end of induction, progression, or death were counted as events. Three pairwise log-rank tests for FFS were monitored with regular pre-planned interim analyses, each maintaining a one-sided 1.67% significance level. A pre-defined decision criterion based on the statistical significance of the treatment comparisons for FFS was established to determine the future treatment recommendation. In 2022, arm A had failed to show FFS-superiority over I and FFS in arm A+I was shown to be superior to A. OS was a secondary outcome and formal pairwise OS comparisons between treatment arms were pre-planned with interim analyses based on O'Brien-Fleming boundaries to maintain pairwise two-sided 5% significance levels. Results: Between July 2016 and December 2020, 870 patients were randomized to arms A (n=288), A+I (n=292), and I (n=290). Median age was 57 years (range 27-68), 76% were male, 87% had stage IV, and 58%/27%/15% had low/intermediate/high risk MIPI. After a median follow-up of 53 months, A+I failed to show FFS-superiority over I (3-year FFS A+I: 86% vs. I: 85%; one-sided p=0.28, hazard ratio: 0.87). FFS-superiority of A over I was again not confirmed with 3-year FFS 75% (A) vs. 85% (I; one-sided p=0.9942, hazard ratio: 1.38). In contrast, the retrospectively calculated two-sided p-value on an overall 5% significance level was consistent with FFS-superiority of I over A (p=0.0102). FFS-superiority of A+I over A was again confirmed with 3-year FFS 86% (A+I) vs. 75% (A; one-sided p=0.0034, hazard ratio: 0.64). Compared with arm A (3-year OS 85%), OS was prolonged in arms A+I and I with 3-year OS of 90% in A+I (p=0.0069, hazard ratio 0.61), and 91% in I (p=0.0041, hazard ratio 0.59). Conclusions: The results confirm superiority of ibrutinib-containing treatment without ASCT (arm I) over ASCT-containing treatment without ibrutinib (arm A) in terms of both, FFS and OS. In the context of ibrutinib- and high-dose cytarabine-containing induction immuno-chemotherapy and ibrutinib maintenance, the addition of ASCT failed to show FFS superiority, while increasing toxicity during maintenance/follow-up. According to the pre-defined decision strategy, ibrutinib+R-CHOP/R-DHAP induction followed by 2 years of ibrutinib maintenance should be the new standard of care in younger MCL patients, thus ending the era of ASCT for MCL patients.

Introduction The TRIANGLE trial (Dreyling et al. 2024) has set a novel standard in first-line treatment of mantle cell lymphoma (MCL) patients aged 18-65 years, highlighting the role of ibrutinib in the management of these patients. During the planning stage of TRIANGLE, results of the LYSA-LYMA trial showed a progression-free survival (PFS) benefit with rituximab maintenance (Rm) after a cytarabine-containing induction and autologous stem cell transplantation (ASCT) in younger patients with MCL (Le Gouill et al. 2017). Therefore, the TRIANGLE trial recommended from the beginning the additional non-randomized administration of Rm (every two months for 3 years) to all three treatment arms (arm I: IR-CHOP/ R-DHAP+ Im; arm A+I: IR-CHOP/ R-DHAP followed by ASCT + Im; arm A, i.e. pre-trial standard of care: R-CHOP/ R-DHAP followed by ASCT) according to national guidelines and/or center practice. We retrospectively analyzed the TRIANGLE data to assess the efficacy and toxicity of additional Rm to ibrutinib-containing regimens, with and without ASCT, and to independently confirm the LYSA-LYMA results in younger, untreated MCL patients. Methods All patients in remission after induction therapy (arm I) and after ASCT (arms A+I, A) were included in this analysis and assigned to Rm or noRm groups based on the as-treated principle. Every treatment arm (arm I,arm A+I, and arm A) was evaluated separately, thus, no adjustment of the alpha level was necessary. The primary endpoint PFS from end of induction (arm I)/end of ASCT (arm A+I, A) was summarized using Kaplan-Meier curves. Differences between Rm and noRm groups within each treatment arm were evaluated using a two-sided log-rank test with an alpha level of 0.05. To address baseline imbalances and to increase power, Cox regression models were calculated including MCL International Prognostic Index (MIPI) (Hoster et al. 2008), response status at the end of induction therapy (CR vs PR after induction/ASCT), Ki67,and cytology (classical vs.pleomorphic/blastoid variant). Results In the different study arms, 59% (n=159; arm I), 64% (n=151; arm A+I) and 67% (n=155; arm A) started Rm. In general, baseline characteristics were well balanced between the Rm and noRm groups in all treatment arms except for more frequent pleomorphic/blastoid cytology in the noRm group of arm I; higher Ki67 in the Rm group of arm A and A+I; and a higher Ann-Arbor stage, and more frequent CR after ASCT in the noRm group of arm A. After a median follow-up time of 4.0 years, median duration of Rm, excluding patients who relapsed, died, or withdrew, was 26 months for arm I and 30 months for arms A+I and A. The Kaplan-Meier curves for PFS and adjusted Cox regression analyses indicated a significantly longer PFS with additional Rm administration in all three treatment arms. The adjusted hazard ratio (Rm vs. noRm) for arm I was 0.50 (95% CI: 0.28 - 0.90, p-value 0.019), for arm A+I 0.26 (95% CI: 0.13 - 0.51, p-value <0.001), and for arm A 0.29 (95% CI: 0.16 - 0.52, p-value <0.001), respectively. Accordingly, the 4-year PFS rate estimated from the Kaplan-Meier curves were for arm I 86% (95% CI: 80% - 92%) in the Rm group vs. 76% (95% CI: 67% - 85%; log rank p=0.016) in the noRm group, for arm A+I 89% (95% CI: 84% - 95%) in the Rm group vs. 75% (95% CI: 65% - 87%; log rank p <0.001) in the noRm group; and for arm A 83% (95% CI: 77% - 89%) in the Rm group vs. 54% (95% CI: 42% - 68%; log-rank p <0.001) in the noRm group. Rm was associated with a modest increase in infectious complications (grade 3 or greater) in all arms (arm I: 25% in the Rm group vs. 12% in the noRm group; arm A+I: 30% in the Rm group vs. 13% in the noRm group; arm A: 19% in the Rm group vs. 1% in the noRm group). In contrast hematological toxicity (grade 3 or greater) was increased only in arm A (28% in the Rm group vs. 11% in the noRm group), whereas comparable frequencies were observed in the other study arms (arm A+I: 46% in the Rm group vs. 52% in the noRm group; arm I: 27% in the Rm group vs 23% in the noRm group). Conclusion This analysis confirms the benefit of Rm, as single maintenance (arm A) as well as in combination with ibrutinib (arms A+ I and I). No unexpected toxicity signals were observed, supporting its use also in combination with novel regimens. On behalf of the European MCL Network *: shared first/senior authorship

This EHA-ESMO Clinical Practice Guideline provides key recommendations for managing primary DLBCL of the CNS.The guideline covers clinical, imaging and pathological diagnosis, staging and risk assessment, treatment and follow-up.Algorithms for first-line and salvage treatments are provided.The author group encompasses a multidisciplinary group of experts from different institutions and countries in Europe.Recommendations are based on available scientific data and the authors' collective expert opinion.

BACKGROUND:Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT. METHODS:The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II-IV mantle cell lymphoma, aged 18-65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m2 on day 1, intravenous doxorubicin 50 mg/m2 on day 1, intravenous vincristine 1·4 mg/m2 on day 1, and oral prednisone 100 mg on days 1-5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1-4, intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1-19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov, NCT02858258. FINDINGS:Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84-92) versus 72% (67-79; hazard ratio 0·52 [one-sided 98·3% CI 0-0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67-79) versus 86% (82-91; hazard ratio 1·77 [one-sided 98·3% CI 0-3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3-5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3-5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238). INTERPRETATION:Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined. FUNDING:Janssen and Leukemia & Lymphoma Society.

Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma (NHL) manifesting in the brain, spinal cord, cerebrospinal fluid and/or eyes, in the absence of systemic manifestations. With an increasing incidence and a 30% 5-year overall survival if promptly treated, timely diagnosis and subsequent treatment is paramount. The typical MRI appearance for PCNSL is a solitary or multiple T2-hypointense, homogeneous gadolinium-enhancing lesion with restricted diffusion. Dexamethasone treatment might compromise and delay the diagnosis. Hallmark of treatment is induction with intravenous high-dose methotrexate consisting polychemotherapy followed by consolidation treatment. Consolidation treatment consists of either whole brain radiotherapy (WBRT) or autologous stem cell transplantation (ASCT). Given the (cognitive) side effects of WBRT, ASCT is increasingly being used as the first choice of treatment.