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Expressed on tumor B cells, CD32b triggers rituximab internalization, and tumor CD32b expression correlates inversely with response to rituximab or rituximab-containing therapy in MCL, FL, and DLBCL. However, approximately 15% of patients are refractory to treatment, and 25% relapse within 3 years following treatment. B Introduction: b Anti-CD20 antibodies, such as rituximab, are an essential therapy resource in patients with B-cell lymphomas. [Extracted from the article]

In HIV-associated B cell lymphomas (HIV+Ly), scanty data are available on the prevalence and prognostic impact of I MYC i rearrangements. DHL/THL were 10 (13 I MYC i + pts did not have data on I BCL2/BCL6 i ): compared to 26 SHL they had similar clinical characteristics, but worse outcome with 5y PFS (30% vs. 60%, I p i = 0.02) and 5y OS (50% vs. 67%, I p i = 0.07). B Introduction: b HIV negative patients (pts) with B cell lymphoma (Ly) carrying I MYC i rearrangements and I BCL2 i +/- I BCL6 i translocations [double hit (DHL) or triple hit Ly (THL)] have shown a dismal prognosis when treated with standard chemotherapy. [Extracted from the article]

• This EHA–ESMO Clinical Practice Guideline provides key recommendations for managing HIV-associated lymphomas. • The guideline covers clinical, imaging and pathological diagnosis; staging and risk assessment; treatment and follow-up. • 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. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cell therapy fails to achieve durable responses in over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients in the third or later line setting. After CAR-T failure, survival outcomes are heterogeneous and a prognostic model in this patient population is lacking. A training cohort of 216 patients with progressive disease (PD) after CAR-T from 12 Spanish centers was used to develop the Post-CAR Prognostic Index (PC-PI); primary endpoint was overall survival (OS) from CAR-T progression. Validation was performed in an external cohort from three different European centers (n = 204). The prognostic score incorporated five variables, assessed at time of PD to CAR-T: ECOG (> 0), hemoglobin (< 10 g/dL), LDH (≥ 2xULN), number of extranodal sites (> 1) and time from CAR-T to PD (< 4 months). Patients were classified in four risk groups with distinct OS (p-value < 0.05 in all comparisons). In the validation cohort, median OS in the low (31%), intermediate-low (26%), intermediate-high (17%) and high risk (26%) were 15.7, 7.1, 1.8 and 1.0 months, respectively (p < 0.05 in all comparisons). Results were consistent following adjustment for subsequent treatment. In the external cohort, the PC-PI showed a C-statistic of 0.79 (95%CI 0.76-0.82), outperforming IPI and R-IPI. In conclusion, the PC-PI score is a novel tool for OS prediction and could facilitate risk-adapted management of LBCL patients relapsing after CAR T-cells. Additionally, these results will help stratification and interpretation of trials and real-world data incorporating CART-exposed patients., (© 2024. The Author(s).)

Chimeric antigen receptor (CAR)-T cell therapy is approved for the treatment of relapsed/refractory (R/R) large B cell lymphoma (LBCL). However, elderly patients might not be candidates for this therapy due to its toxicity, and criteria for candidate selection are lacking. Our aim was to analyze efficacy and toxicity results of CAR-T cell therapy in the population of patients 70 years and older as compared to those obtained in younger patients in the real-world setting. A multicentric retrospective study was performed including patients with R/R aggressive LBCL who received commercial CAR-T cell therapy with either tisagenlecleucel or axicabtagene ciloleucel within the Spanish Group of Hematopoietic Transplant and Cell Therapy/Spanish Group of Lymphomas and Autologous Transplant (GETH-TC/GELTAMO) centers between 2019 and 2023. As of August 2023, 442 adult patients with aggressive LBCL underwent apheresis for CAR-T cell therapy as third or subsequent line and follow-up data was collected. Of 412 infused patients, 71 (17%) were 70 years or older. Baseline characteristics, product selection, and characteristics at apheresis (including disease status, Ann Arbor stage, revised international prognosis index (R-IPI), bulky disease, lactate dehydrogenase [LDH] and ECOG [Eastern Cooperative Group performance status]) were comparable between groups. Median time from both approval to infusion and apheresis to infusion did not differ. No differences were found between groups in overall and complete response rates at 1 and 3 months. With a median follow-up of 12.2 months (range 1-44), 12-month progression-free survival (PFS) and overall survival (OS) were comparable between groups (35.2% in <70 years vs. 35.9% in ≥70 years (P = .938) and 51.1% and 52.1% (P = .885), respectively). Age ≥70 years did not affect PFS (hazard ratio (HR) 0.98, P = .941) and OS (HR 0.97, P = .890) in the univariate and multivariate analysis. Cytokine release syndrome (CRS) was observed in 82% of patients <70 years old and 84.5% in ≥ 70 years old (P = .408). Grade ≥3 CRS was more frequent in the older group (5% vs. 15%, P = .002). In the multivariate analysis, age ≥70 years was associated with an increased risk of grade ≥3 CRS (OR 3.7, P = .013). No differences were observed in terms of overall neurotoxicity (35% vs. 42%, P = .281) or grade ≥3 (12% vs. 17%, P = .33). The proportion of patients with infections, admission to the intensive care unit within the first month, and non-relapse mortality were similar between both groups. CAR-T cell therapy in patients older than 70 years showed similar efficacy to that observed in younger patients in the real-world setting. However, age ≥70 years was an independent risk factor for grades 3-4 CRS. The need for additional strategies to reduce toxicity in this population should be addressed in future studies., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

This EHA-ESMO Clinical Practice Guideline provides key recommendations for managing HIV-associated lymphomas.The guideline covers clinical, imaging and pathological diagnosis; staging and risk assessment; treatment and follow-up.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., Competing Interests: KH reports personal fees for advisory board membership from Gilead, Hexal, Incyte, Miltenyi, Novartis, Recordati and Roche; personal fees as an invited speaker from BeiGene, Bristol Myers Squibb (BMS), Novartis, Recordati, Roche and Servier; personal fees for a writing engagement from Hexal; institutional fees as coordinating Principal Investigator (PI) from Incyte and Roche; a non‐renumerated role as working group chair of the German Society of Hematology and Medical Oncology (DGHO); non‐remunerated advisory role for the European Hematology Association (EHA) Education Committee; and a non‐remunerated leadership role for the German Lymphoma Alliance. MB reports personal fees as an invited speaker from BMS, EUSA Pharma, Gilead, Janssen, Merck and ViiV Healthcare. IA reports personal fees for advisory board membership from AbbVie, AstraZeneca, Eli Lilly, Genesis/Incyte, Janssen, Novartis, Roche, Sobi and Takeda; personal fees as an invited speaker from AbbVie, AstraZeneca, Eli Lilly, Genesis/Incyte, Janssen, Novartis, Roche, Sandoz, Sobi and Takeda; non‐remunerated leadership roles for the Croatian Cooperative Group for Hematologic Diseases and the EHA Lymphoma Specialized Working Group; and non‐renumerated membership of the Board of Directors of the Croatian Hematological Society and the European Lymphoma Institute. MBO reports personal fees for advisory board participation from Kite Pharma, Novartis and Roche; personal fees as an invited speaker from Janssen, Kite Pharma, Roche and Takeda; a personal and institutional research grant from Kite Pharma (Gilead/Kite Pharma award); and non‐renumerated leadership roles for the Spanish Lymphoma Group (GELTAMO; coordinator of the Aggressive Group and member of the Scientific Committee), the Madrid Hematology Society (member of the Board of Directors, treasurer) and the Spanish Society of Hematology and Hemotherapy (member of the Board of Directors, accountant). CBe reports personal fees for expert testimony from Janssen. UB reports personal fees for advisory board membership from Janssen‐Cilag; personal fees as an invited speaker from AstraZeneca and Janssen‐Cilag; personal fees for writing engagements from AbbVie and AstraZeneca; travel grants from AbbVie, BeiGene and Gilead; compensation for congress registration fees from Lilly; a non‐renumerated role as PI for Regeneron and Roche; and non‐renumerated membership of DGHO, the German Cancer Society (DKG) and EHA. CC reports no conflicts of interest. SC reports employment as a treatment advocate by the charity HIV i‐Base. KC reports personal fees for advisory board membership from AbbVie, Atara, Celgene, Incyte, Janssen, Kite, Roche and Takeda; personal fees as an invited speaker and personal travel grants/conference support from Celgene, Incyte, Kite, Roche and Takeda; personal fees for consulting from Atara, Celgene, Incyte and Kite. ADP reports institutional fees as an invited speaker from Gilead (non‐promotional teaching). MH reports personal fees for advisory board membership from Amgen, EUSA Pharma, Sanofi, Stemline and Takeda; and personal fees as an invited speaker from EUSA Pharma, Gilead, Janssen, Jazz Pharmaceuticals and Sanofi. CH reports personal fees for advisory board membership and as an invited speaker from EUSA Pharma, Gilead Sciences, Janssen‐Cilag, MSD and ViiV Healthcare; and institutional fees as local PI (for clinical studies conducted at institution) from Janssen‐Cilag, MSD and ViiV Healthcare. MJK reports institutional fees for advisory board membership from Adicet Bio, BMS/Celgene, Galapagos, Kite (a Gilead Company), Miltenyi Biotec and Novartis; institutional fees as an invited speaker from BeiGene, BMS/Celgene, Kite (a Gilead Company) and Novartis; institutional fees as local PI from BMS/Celgene; institutional fees as coordinating PI from Galapagos, Kite (a Gilead Company), Miltenyi Biotec and Novartis, and an institutional travel grant from AbbVie. SM reports personal fees for participation in a Data Monitoring Committee from Bayer. JTN reports personal fees for advisory board membership from Recordati Rare Diseases EUSA Pharma; personal fees as an invited speaker from Novartis and Recordati Rare Diseases EUSA Pharma; a personal research grant from Gilead Spain; and institutional funding from Recordati Rare Diseases EUSA Pharma. EO reports personal fees as an expert for grant attributions from CSL Behring; personal fees as a consultant from EUSA Pharma; an institutional research grant on unicentric Castleman disease pathogenesis from the Castleman Disease Collaborative Network (CDCN); and non‐renumerated membership of the advisory board of CDCN. AR reports personal fees for advisory board membership from Incyte, Italfarmaco and Takeda; personal fees as an expert discussant from Janssen and Servier; personal fees as an invited speaker from Sobi and Takeda; institutional fees as local PI from MSD, Pharmacyclis and Sanofi. JMR reports personal fees for advisory board membership from Amgen, Pfizer, Shire and Takeda; personal fees as an invited speaker from Amgen; and personal fees as local PI from Takeda. PS reports personal fees as an invited speaker from MSD and ViiV Healthcare; and a personal and institutional research grant from Gilead Sciences. BvT reports personal fees for advisory and consultancy roles for Allogene, Amgen, BMS/Celgene, Cerus, Gilead Kite, Incyte, IQVIA, Janssen‐Cilag GmbH, Lilly, Miltenyi, MSD, Noscendo, Novartis, Pentixapharm, Pfizer, Pierre Fabre, QualWorld, Roche, Sobi and Takeda; personal fees as an invited speaker from AbbVie, AstraZeneca, BMS/Celgene, Gilead Kite, Incyte, Lilly, MSD, Novartis, Roche Pharma AG and Takeda; institutional funding from Esteve, MSD, Novartis and Takeda; and travel support from AbbVie, AstraZeneca, Gilead Kite, Lilly, MSD, Pierre Fabre, Roche, Takeda and Novartis. CBu reports personal fees for advisory board membership from AbbVie, BeiGene, Celltrion, Gilead Sciences, Incyte, Janssen, Lilly Deutschland GmbH, MorphoSys, Novartis, Pfizer, Regeneron, Roche and Sobi; personal fees as an invited speaker from AbbVie, BeiGene, Celltrion, Gilead Sciences, Incyte, Janssen, Lilly Deutschland GmbH, MorphoSys, Novartis, Pfizer, Regeneron, Roche and Sobi; and institutional funding from AbbVie Amgen, Bayer, Celltrion, Janssen, MSD, Pfizer and Roche (all for investigator‐sponsored clinical trials and registries). MD reports personal fees as an advisory board member from AbbVie, AstraZeneca, BeiGene, BMS/Celgene, Gilead, Janssen, Lilly/Loxo, Novartis and Roche; personal fees as an invited speaker for AstraZeneca, BeiGene, Gilead/Kite, Janssen, Lilly, Novartis and Roche; institutional research grants from AbbVie, Bayer, Celgene, Janssen, Lilly and Roche; institutional funding from Gilead/Kite; and non‐renumerated membership of the American Society of Clinical Oncology, American Society of Hematology (subcommittee), DGHO (prior Board member), EHA (Executive Board), ESMO (Faculty) and the Lymphoma Research Foundation (Mantle Cell Lymphoma Consortium). AD reports personal fees as an advisory board member for AbbVie, Acerta Pharma, AstraZeneca, BMS/Celgene, Genmab, Gilead, Incyte, Karyopharm, Kite Pharma, Regeneron, Roche, Sobi and Takeda; personal fees as an invited speaker for AstraZeneca, Gilead and Roche; institutional research grants for conduct of commercial research and funding of IST from Acerta Pharma and Roche; institutional research grants for conduct of commercial research from ADC Therapeutics, AstraZeneca, BMS/Celgene, Gilead and Pfizer; institutional research grant from MSD (no financial interest); non‐renumerated leadership role, member and UK Board representative for the Precision Medicine in Aggressive Lymphoma Consortium of the International Extranodal Lymphoma Study Group; advisory role and international advisor for the Swiss SAKK Lymphoma Project Group and member of the UK National Cancer Research Institute's High Grade Lymphoma Study Group., (© 2024 The Authors. Published by John Wiley & Sons Limited on behalf of European Hematology Association and by Elsevier Limited on behalf of European Society for Medical Oncology.)

Competing Interests: The authors declare no conflict of interest.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and R-bendamustine (R-B) are the most common frontline treatment strategies for advanced-stage follicular lymphoma (FL). After R-CHOP induction therapy, using rituximab for maintenance therapy notably improves outcomes; however, whether this can be achieved by using the same approach after R-B therapy is still being determined. This retrospective analysis compared 476 FL patients from 17 GELTAMO centers who received R-based regimens followed by rituximab maintenance therapy for untreated advanced-stage FL. The complete response rate at the end of induction was higher with R-B and relapses were more frequent with R-CHOP. During induction, cytopenias were significantly more frequent with R-CHOP and so was the use of colony-stimulating factors. During maintenance therapy, R-B showed more neutropenia and infectious toxicity. After a median follow-up of 81 months (95% CI: 77-86), the 6-year rates of progression-free survival (PFS) were 79% (95% CI: 72-86) for R-bendamustine vs. 67% (95% CI: 61-73) for R-CHOP ( p = 0.046), and 6-year overall survival (OS) values were 91% (95% CI: 86-96) for R-B vs. 91% (95% CI: 87-94) for R-CHOP ( p = 0.49). In conclusion, R-B followed by rituximab maintenance therapy in patients with previously untreated FL resulted in significantly longer PFS than R-CHOP, with older patients also benefiting from this treatment without further toxicity. Adverse events during maintenance were more frequent with R-B without impacting mortality.

Chimeric antigen receptor T cells (CAR-T) has emerged as a promising therapy, over 60% of patients fail to sustain a long-term response. The underlying factors that leads to the effectiveness of this therapy are not completely understood, CAR-T cell persistence and monitoring seems to be pivotal for ensuring a successful response. Various monitoring methods such as multiparametric flow cytometry (MFC) or quantitative PCR (qPCR) have been applied. Our objective is to develop digital PCR (dPCR) assays for detection and quantification of CAR-T cells, comparing them with MFC and qPCR. Samples taken at different follow-up times from 45 patients treated with CAR-T therapy were analyzed to assess the correlation between the different methodologies. dPCR presented a high correlation with MFC and qPCR (r = 0.97 and r = 0.87, respectively), while offering a higher sensitivity (0.01%) compared to MFC (0.1%) and qPCR (1%). dPCR emerged as an alternative and highly sensitivity method for monitoring CAR-T cell dynamics. This technique is well-suited for implementation in clinical practice as a complementary technique to MFC., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Abstract: Large B-cell lymphoma (LBCL) carrying MYC rearrangement, alone or together with BCL2 and/or BCL6 translocations, have shown a poor prognosis when treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in the HIV population. Scanty data are available on the prevalence and prognostic impact of MYC rearrangements in HIV-associated LBCL. We conducted a retrospective study to evaluate the clinical effect of MYC rearrangement in HIV-associated LBCL. We evaluated clinical characteristics, treatment received, and outcome of LBCL in patients with HIV with MYC rearrangement (MYC+) and without MYC rearrangement (MYC-). A total of 155 patients with HIV who had received fluorescence in situ hybridization analysis for MYC were enrolled in 11 European centers: 43 with MYC+ and 112 MYC-. Among patients with MYC, 10 had double-/triple-hit lymphomas, and 33 had isolated MYC rearrangement (single-hit lymphoma). Patients with MYC+ had more frequently advanced stage, >2 extranodal site at presentation, and higher proliferative index. There were no significant differences in overall survival and progression-free survival (PFS) between the 2 groups. However, patients with MYC+ received more frequently intensive chemotherapy (iCT) (44%) than (R)CHOP alone (35%) or infusional treatment (DA-EPOCH-R and R-CDE) (19%). Among patients with MYC+, those who received iCT achieved a better outcome than patients who received nonintensive treatment (complete remission, 84% vs 52%; P = .028; 5-year PFS, 66% vs 36%; P = .021). Our retrospective results suggest that HIV-associated LBCL with MYC+ could be considered for an intensive therapeutic approach whenever possible, whereas (R)CHOP seems to give inferior results in this subset of patients in terms of complete remission and PFS., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

High dose-intensive or infusional intermediate-dose immunochemotherapy is highly effective treatment for Burkitt lymphoma irrespective of human immunodeficiency virus (HIV) infection. However, toxicities of these regimens are relevant, especially in older adults and elderly patients. The prospective multicenter BURKIMAB14 trial included four to six blocks of immunochemotherapy according to stage (localized: 1 and 2 non-bulky; advanced: 2 bulky, 3, 4) and age, with dose reduction in patients >55 years old. Dose-intensity of chemotherapy was reduced in patients ≤55 years old after achieving complete metabolic response (CMR). Their outcomes were compared with those of similar patients included in the former BURKIMAB08 trial, in which there was no dose reduction. CMR was attained in 86 of 107 (80%) patients (17/19 in localized stages and 69/88 in advanced stages). Patients from the BURKIMAB14 trial ≤55 years old showed similar overall survival (OS), fewer infections and cytopenias than patients from the BURKIMAB08 trial. Patients >55 years old had a significantly higher treatment- related mortality despite dose reduction of chemotherapy. With a median follow-up of 3.61 years the 4-year OS probability was 73% (range, 63-81%). Age (≤55 vs. >55 years) and stage (localized vs. advanced) had prognostic significance. No significant differences in OS were observed in HIV-positive versus HIV-negative patients. The results of BURKIMAB14 are similar to those of other dose-intensive immunochemotherapy trials. Age >55 years and advanced stage, but not HIV infection, were associated with poor survival. Dose reduction of chemotherapy in young adults in CMR is safe and does not impact outcomes (clinicaltrials gov. Identifier: NCT05049473).

Background: Diffuse large B-cell lymphoma comprises nearly 30% of non-Hodgkin lymphoma cases and patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for stem-cell transplantation have few treatment options and poor prognoses. We aimed to determine whether the novel combination of polatuzumab vedotin in combination with rituximab and lenalidomide (Pola+R+Len) would provide a tolerable treatment option with enhanced antitumour response in patients with relapsed or refractory diffuse large B-cell lymphoma., Methods: This completed phase 1b/2, open-label, multicentre, single-arm study (GO29834) evaluated the safety and efficacy of Pola+R+Len in patients with relapsed or refractory diffuse large B-cell lymphoma at 19 sites in three countries (USA, Spain, and UK). Patients (≥18 years old) were eligible for inclusion if they had histologically documented CD20-positive relapsed or refractory diffuse large B-cell lymphoma and Eastern Cooperative Oncology Group performance status of 2 or lower, had received at least one previous line of chemoimmunotherapy, including an anti-CD20 agent, and were ineligible for stem-cell transplantation. The dose-escalation phase (1b) used escalating doses of lenalidomide to find the recommended phase 2 dose. Patients received six 28-day cycles of induction treatment with intravenous rituximab 375 mg/m 2 and intravenous polatuzumab vedotin 1·8 mg/kg (all cohorts) plus oral lenalidomide at the following doses: 10 mg (cohort A); 15 mg (cohort B); and 20 mg (cohort C). Rituximab and polatuzumab vedotin were administered on day 1 and lenalidomide on days 1-21 of each 28-day cycle. During the dose-expansion phase (2), patients received six 28-day cycles of Pola+R+Len at the recommended phase 2 dose established during dose escalation. In both phases, patients with a complete response or partial response at the end of induction were eligible for post-induction therapy with rituximab 375 mg/m 2 on day 1 and lenalidomide 10 mg/day on days 1-21 of each 28-day cycle for a maximum of 6 cycles. The primary safety objective of the dose-escalation phase was identification of the maximum tolerated dose through incidence of dose-limiting toxic effects. The primary efficacy outcome of the dose-expansion phase was Independent Review Committee-assessed complete response rate at end of induction, based on PET-CT. Analyses were conducted in the safety population, which included all patients who received at least one dose of any study drug, and the efficacy population, which included all patients who received at least one dose of any study drug at the recommended phase 2 dose. This study is registered with ClinicalTrials.gov, number NCT02600897., Findings: Between July 11, 2017 and Feb 3, 2020, 57 patients were enrolled (median age 71 years [IQR 60-75]; 38 [67%] were male and 19 (33%) were female; 47 [82%] were not Hispanic or Latino; and the median previous lines of therapy was 2 [IQR 1-3]). 18 participants were included in phase 1b and 39 were included in phase 2. Phase 1b confirmed a 20 mg recommended phase 2 dose for lenalidomide. After a median follow-up of 11·8 months (IQR 4·7-25·8), the complete response rate, as assessed by the Independent Review Committee, was 31% (90% CI 20-43). The most common grade 3-4 adverse events were neutropenia (35 [61%] of 57) and thrombocytopenia (eight [14%] of 57). Serious adverse events were reported in 23 (40%) of 57 patients and one patient died due to a treatment-related adverse event (neutropenic sepsis)., Interpretation: Although the combination of Pola+R+Len did not meet the prespecified activity threshold, some patients derived clinical benefit and the regimen had a tolerable safety profile in patients with relapsed or refractory diffuse large B-cell lymphoma., Funding: Genentech/F Hoffmann-La Roche., Competing Interests: Declaration of interests PA has held consultancy for and received honoraria from Janssen, AstraZeneca, Bristol Myers Squibb, AbbVie, Genmab and F Hoffmann-La Roche; and has received honoraria from Gilead and Incyte and expenses for travel from AbbVie, Janssen, and F Hoffmann-La Roche. CP has received honoraria from Celgene/Bristol Myers Squibb, Novartis, F Hoffmann-La Roche, AbbVie, Janssen, and Gilead/Kite; received expenses for travel from F Hoffmann-La Roche, Gilead/Kite, and AbbVie; and participated on a Data Safety Monitoring Board or Advisory Board with F Hoffmann-La Roche, Incyte, and BeiGene. JMAP has received honoraria from F Hoffmann-La Roche, Janssen, AbbVie, AstraZeneca, and Amgen. AM has received honoraria for advisory boards from SOBI, Amgen, F Hoffmann-La Roche, and Takeda; received payment or honoraria for lectures, presentations, or speaker bureaus from F Hoffmann-La Roche and Takeda; received payment for expert testimony from Delphi Study: Prosthetics; and received support for attending meetings and/or travel from F Hoffmann-La Roche and Takeda. ES reports expenses for travel and attending meetings from Flatiron Health and BeiGene, and stock or stock options from F Hoffmann-La Roche and BeiGene; is an employee of BeiGene; and was an employee of Wayne State University/Karmanos Cancer institute from September, 2017 to February, 2021, and of Flatiron Health from February, 2021, to March, 2023. HYJ, JH, and LM are employees of Genentech and own F Hoffmann-La Roche stock options. JdG was an employee of Genentech at the time of this analysis. CD has held consultancy for Genentech/F Hoffmann-La Roche; and participated on a Data Safety Monitoring Board or Advisory Board with Genentech/F Hoffmann-La Roche and Celgene (BMS). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In the pre-chimeric antigen receptor T cell (CAR-T) therapy era, the SCHOLAR-1 study identified a group of patients with refractory aggressive B cell lymphoma (ABCL) with particularly poor prognoses. We recently published our real-world data from Spain, focused on this SCHOLAR-1 refractory group, and compared patients who underwent CAR-T therapy with the previous standard of care. In this study, we found that the efficacy of CAR-T therapy in refractory patients, in terms of progression-free survival (PFS) and overall survival (OS), was superior to that of the treatments available in the pre-CAR-T era. The main objective of these new analyses was to analyze treatment efficacy in terms of response rates and survival for patients with ABCL with or without the SCHOLAR-1 criteria. In addition, we analyzed the prognostic impact of each SCHOLAR-1 criterion independently. Our study aimed to assess the prognostic impact of SCHOLAR-1 criteria on ABCL patients treated with CAR-T therapy in Spain. This multicenter, retrospective, observational study. We included all adult patients treated with commercially available CAR-T cell products and diagnosed with ABCL different from primary mediastinal large B cell lymphoma between February 2019 and July 2022. Patients meeting any SCHOLAR-1 criteria (progressive disease as the best response to any line of therapy, stable disease as the best response to ≥4 cycles of first-line therapy or ≥2 cycles of later-line therapy, or relapse at <12 months after autologous stem cell transplantation [auto-SCT]) in the line of treatment before CAR-T therapy (SCHOLAR-1 group) were compared with those not meeting any of these criteria (non-SCHOLAR-1 group). To analyze the prognostic impact of individual SCHOLAR-1 criteria, all the patients who met any of the SCHOLAR-1 criteria at any time were included to assess whether these criteria have the same prognostic impact in the CAR-T era. In addition, patients were grouped according to whether they were refractory to the first line of treatment, refractory to the last line of treatment, or relapsed early after auto-SCT. The PFS and OS were calculated from the time of appearance of the SCHOLAR-1 refractoriness criteria. Of 329 patients treated with CAR-T (169 with axi-cel and 160 with tisa-cel), 52 were in the non-SCHOLAR-1 group and 277 were in the SCHOLAR-1 group. We found significantly better outcomes in the non-SCHOLAR-1 patients compared with the SCHOLAR-1 patients (median PFS of 12.2 and 3.3 months, respectively; P = .009). In addition, axi-cel showed better results in terms of efficacy than tisa-cel for both the non-SCHOLAR-1 group (hazard ratio [HR] for PFS, 2.7 [95% confidence interval (CI), 1.1 to 6.7; P = .028]; HR for OS, 7.1 [95% CI, 1.5 to 34.6; P = .015]) and SCHOLAR-1 group (HR for PFS, 1.8 [95% CI, 1.3 to 2.5; P < .001]; HR for OS, 1.8 [95% CI, 1.2 to 2.6; P = .002]), but also significantly more toxicity. Finally, separately analyzing the prognostic impact of each SCHOLAR-1 criterion revealed that refractoriness to the last line of treatment was the variable with the most significant impact on survival. In conclusion, SCHOLAR-1 refractoriness criteria notably influence the efficacy of CAR-T therapy. In our experience, axi-cel showed better efficacy than tisa-cel for both SCHOLAR-1 and non-SCHOLAR-1 patients. Refractoriness to the last line of treatment was the variable with the most significant impact on survival in the CAR-T therapy era., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Parsaclisib, a potent and highly selective PI3Kδ inhibitor, has shown clinical benefit in patients with relapsed or refractory (R/R) B-cell malignancies. This phase 2 study (CITADEL-203; NCT03126019, EudraCT 2017-001624-22) assessed efficacy and safety of parsaclisib monotherapy in patients with R/R follicular lymphoma (FL)., Methods: Patients ≥18 years of age with histologically confirmed R/R FL (grade 1-3a) and prior treatment with ≥2 systemic therapies received parsaclisib 20 mg once daily (QD) for 8 weeks then parsaclisib 20 mg once weekly (weekly dosing group [WG]) or parsaclisib 20 mg QD for 8 weeks then parsaclisib 2.5 mg QD (daily dosing group [DG]); DG was selected for further assessment. Primary endpoint was objective response rate (ORR)., Findings: At data cut-off (January 15, 2021), 126 patients had been treated (WG: n = 23; DG: n = 103). ORR (95% confidence interval [CI]) was 77.7% (68.4-85.3) with a complete response rate (95% CI) of 19.4% (12.3-28.4) in DG; median (95% CI) duration of response was 14.7 months (10.4-not estimable [NE]), median progression-free survival was 15.8 months (11.0-NE), and median overall survival was not reached. The most common any-grade treatment-emergent adverse events (TEAEs) among all treated patients included diarrhoea (n = 48, 38.1%), nausea (n = 31, 24.6%), and cough (n = 28, 22.2%); the most common grade ≥3 TEAEs were diarrhoea (n = 15, 11.9%), neutropenia (n = 13, 10.3%), and colitis (n = 7, 5.6%). Dose interruption, reduction, and discontinuation from TEAEs occurred in 46.8% (n = 59), 17.5% (n = 22), and 23.8% (n = 30) of patients, respectively., Interpretation: Treatment with parsaclisib demonstrated rapid and durable responses, and a manageable safety profile in patients with R/R FL., Funding: Incyte Corporation., Competing Interests: Marek Trněný—Consultancy: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Gilead Sciences, Incyte Corporation, Janssen, MorphoSys, Roche, and Takeda. Honoraria: AbbVie, Amgen, Bristol Myers Squibb, Gilead Sciences, Incyte Corporation, Janssen, MorphoSys, Roche, and Takeda. Travel, accommodations, or expenses: AbbVie, Bristol Myers Squibb, Gilead Sciences, Janssen, Roche, and Takeda. Research funding: Roche. Abraham Avigdor—Consultancy: Gilead Sciences, Pfizer, and Takeda. Honoraria: Gilead Sciences, Pfizer, and Takeda. Research funding: Bristol Myers Squibb and Janssen. Matthew S. McKinney—Consultancy: BTG Specialty Pharmaceuticals, Celgene, Genentech, Molecular Templates, Pharmacyclics, and Verastem Oncology. Honoraria: Genentech and Kite Pharma/Gilead Sciences. Research funding: BeiGene, Celgene, Genentech, Incyte Corporation, Molecular Templates, Nordic Nanovector, and Novartis. Speakers bureau: Kite Pharma/Gilead Sciences. Shankara Paneesha—Honoraria: AbbVie, Bristol Myers Squibb, Celgene, Gilead Sciences, and Janssen. Björn E. Wahlin—Consultancy: Roche. Research funding: Gilead Sciences and Roche. David Cunningham—Advisory committee: OVIBIO. Research funding: 4SC, Amgen, AstraZeneca, Bayer, Celgene, Clovis Oncology, Eli Lilly & Company, Janssen, MedImmune, Merck, Merrimack Pharmaceuticals, and Sanofi. Nicholas Morley—Advisory board: Roche. Honoraria: Kite Pharma and Janssen. Conference support: AbbVie, Roche, and Takeda. Miguel Canales—Honoraria: BeiGene, Celgene, Gilead Sciences, Incyte Corporation, Janssen, Karyopharm, Kyowa, Novartis, Sandoz, and Takeda. Speakers' bureau: Amgen, Janssen, Kyowa, Roche, Sandoz, and Takeda. Mariana Bastos-Oreiro—Honoraria: Bristol Myers Squibb/Celgene, Gilead Sciences, Janssen, Novartis, and Roche. Research funding: Roche. Speakers’ bureau: Bristol Myers Squibb/Celgene, Janssen, Kite Pharma, Roche, Novartis, and Takeda. David Belada—Consultancy: Gilead Sciences, Janssen, Roche, and Takeda. Board of Directors or Advisory committee: Gilead Sciences, Janssen, Roche, and Takeda. Travel expenses: Gilead Sciences, Roche, and Takeda. Research funding: Celgene, Gilead Sciences, Janssen, Roche, and Takeda. Fred Zheng—Employment and stock ownership: Incyte Corporation. Douglas J. DeMarini—Former employment and stock ownership: Incyte Corporation. Wei Jiang—Former employment and stock ownership: Incyte Corporation. Ping Jiang—Former employment and stock ownership: Incyte Corporation. Ryan C. Lynch—Consultancy: MorphoSys. Research funding: Bayer, Cyteir Therapeutics, Genentech, Incyte Corporation, Juno Pharmaceuticals, Rhizen Pharmaceuticals, Takeda, and TG Therapeutics. John S. Hrom and Liliana Devizzi—No relevant financial relationships to disclose., (© 2023 The Authors.)

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., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

We propose a novel biomarker that can identify patients at high risk of early progression after chimeric antigen receptor (CAR) T cell therapy. Calculation of cell-free DNA (cfDNA) with a pre-apheresis (PA) and pre-lymphodepletion (PL) sample allows monitoring of tumor dynamics (∆cfDNA). In the present study, ∆cfDNA and other biomarkers and clinical variables were evaluated in 58 patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL). ∆cfDNA (>11 ng/mL plasma; P =.003), C-reactive protein (CRP) PL (>1.06 mg/dL; P = .004), lactate dehydrogenase (LDH) PL (>304; P = .006), disease status PL (progressive disease; P = .035) and sex (male; P = .016) were highly correlated with 1 month progression. After adjusting for ∆cfDNA, CRP PL, and LDH PL, disease status PL, and sex, ∆cfDNA remained associated with 1-month progression after CAR T cell infusion., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)