Our study demonstrates that our local population has similar clinicopathological and prognostic characteristics of DLBCL as compared to global findings. It also highlights the limitations of R-CHOP(-like) regimens in contemporary DLBCL management and therefore an ongoing need for improved therapeutic strategies.

The patient was treated with six cycles of the R-CHOP regimen (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone), achieving complete metabolic remission as confirmed by positron emission tomography-computed tomography. Through our literature review of additional six cases of primary seminal vesicle lymphoma, we aim to elucidate the typical clinical presentations, imaging features, pathological characteristics, genetic mutations, and therapeutic strategies, aiming to contribute to better detection and management of this rare malignancy. This case underscores the diagnostic challenges and emphasizes the necessity for heightened clinical suspicion and definitive pathological examination in the management of primary seminal vesicle lymphoma.

Complete remission was achieved with a reduced immunomodulatory drug dosage and rituximab therapy. She has been alive for 8 months postoperatively without recurrence. This case suggests that PTLD should be considered in assessing patients presenting with abdominal symptoms following organ transplantation.

P1/2, N=316, Recruiting, Simcha IL-18, Inc. | Active, not recruiting --> Recruiting | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Jun 2025

The association of Cladribine (CDA) with rituximab (R) is the standard first-line treatment in fit HCL and HCL variant patients. BRAF and BTK inhibitors are options in relapsed/refractory HCL patients. The optimal treatment sequences remain to be determined.

P2, N=150, Not yet recruiting, PolTREG S.A.

P2, N=15, Active, not recruiting, Bnai Zion Medical Center | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2024 --> Dec 2024

P3, N=152, Active, not recruiting, Biocad | Recruiting --> Active, not recruiting | Trial completion date: Feb 2025 --> Feb 2026

P1, N=154, Completed, Xencor, Inc. | Active, not recruiting --> Completed | N=270 --> 154 | Trial completion date: Jan 2025 --> Apr 2024 | Trial primary completion date: Oct 2024 --> Apr 2024

Six weeks later, while receiving the CD20-directed immunotherapies glofitamab and obinutuzumab, another bone marrow biopsy revealed eradication of the B-ALL and new involvement by pure erythroid leukemia (PEL). This patient's B-ALL lacked an IGH::BCL2 fusion resulting from t(14; 18), suggesting it did not arise through transformation of his prior FL/DLBCL. Instead, the B-ALL was likely caused by his extensive exposure to genotoxic chemotherapy drugs – including alkylating agents – for his preceding lymphomas. The shared cytogenetic and molecular features between this patient's B-ALL and PEL imply they are clonally related.

P1, N=20, Completed, Noah Merin | Active, not recruiting --> Completed | N=30 --> 20 | Trial completion date: Nov 2031 --> Nov 2024

P2, N=40, Recruiting, The First Affiliated Hospital of Soochow University

P=N/A, N=60, Completed, Shandong Provincial Hospital for Skin Diseases & Shandong First Medical University; Shandong Provincial Hospital for Skin Diseases & Shandong

P4, N=58, Completed, The First Affiliated Hospital of Zhejiang University School of Medicine; The First Affiliated Hospital of Zhejiang University School of Medicine

P4, N=54, Recruiting, West China Hospital, Sichuan University; West China Hospital, Sichuan University

P3, N=428, Not yet recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

P2, N=170, Not yet recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P2, N=30, Completed, Peking University People's Hospital; Peking University People's Hospital | Not yet recruiting --> Completed

P2, N=132, Completed, Peking University People's Hospital; Department of Neurology, Peking University People’s Hospital | Not yet recruiting --> Completed

P2, N=120, Completed, Peking University People's Hospital; Department of Neurology, Peking University People’s Hospital | Not yet recruiting --> Completed

P2, N=124, Completed, Peking University People's Hospital; Department of Neurology, Peking University People’s Hospital | Not yet recruiting --> Completed

P2/3, N=210, Recruiting, University of Birmingham | Active, not recruiting --> Recruiting

P2, N=125, Recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Active, not recruiting --> Recruiting | N=80 --> 125 | Trial primary completion date: Sep 2027 --> Apr 2025

P1, N=40, Recruiting, IGM Biosciences, Inc. | N=24 --> 40 | Trial completion date: Jul 2025 --> May 2026 | Trial primary completion date: Feb 2025 --> May 2025

P3, N=105, Active, not recruiting, Biocad | Recruiting --> Active, not recruiting | Trial completion date: Apr 2025 --> Sep 2026 | Trial primary completion date: Sep 2024 --> Jan 2025

P2, N=17, Completed, University College, London | Trial completion date: Jun 2023 --> Feb 2024

P2, N=18, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2024 --> Sep 2025

P1, N=30, Not yet recruiting, National Heart, Lung, and Blood Institute (NHLBI)

P3, N=500, Not yet recruiting, Hoffmann-La Roche

All pts received obinutuzumab pretreatment (1000mg or 2000mg) on Cycle (C) 1 Day (D) 1. Glofitamab induces high response rates in pts with heavily pretreated R/R MCL, including those who have clinical and/or histological features associated with poor prognosis. Clinical and molecular remissions are achieved early in the course of treatment, with durable responses lasting beyond the length of the treatment.

The combination of the Bruton tyrosine kinase inhibitor (BTKi) ibrutinib, the BCL-2 inhibitor venetoclax (V), and the anti-CD20 monoclonal antibody (mAb) obinutuzumab (O) has demonstrated safety and efficacy in R/R and TN MCL (Le Gouill, Blood 2021). AVO is safe and active in pts with R/R and TP53-aberrant/transplant ineligible TN MCL. Preliminary efficacy and feasibility of an MRD-guided treatment approach is encouraging in this high-risk TN cohort B. Our data supports further investigation of a targeted triplet approach, and the phase II TN transplant eligible and TP53 wild type cohort is enrolling based on demonstrated safety and efficacy in cohort B. Updated results will be presented at the meeting.

Introduction – We previously reported the efficacy and safety results of a combination of ibrutinib with rituximab in patients (pts) with mantle cell lymphoma (MCL) ≥ 65 years. Conclusions – Chemotherapy-free frontline therapy with AR is highly effective, safe, induces deep MRD negative responses and alters immune landscape in older pts with MCL. Randomized studies are needed to confirm whether this regimen can be the new first line standard treatment for older MCL patients.

After transformation, tFL samples showed a reduction in T follicular helper cells (p=0.008) and an increase in immunosuppressive M2-like macrophages and neutrophils (p<0.001 and p=0.028, respectively). By elucidating the distinct molecular and immune landscapes of FL at the time of diagnosis and transformation, this study underscores the importance of immune microenvironment in FL transformation and patient outcome.

Two pts were switched to zanubrutinib due to PD on U2, both achieved response. AU2 is a highly effective regimen in pts with previously untreated MCL, including those with high-risk genetics (100% CR rate), and achieves a high molecular uMRD rate. Pts who develop progressive disease can be effectively salvaged with subsequent therapies.

Three pts were unevaluable for progression at 2y due to non-progression events including a second malignancy, sudden death, and hemolytic anemia requiring rituximab... Circulating tumor DNA is detectable in baseline plasma of >90% pts with untreated FL. Quantitative ctDNA levels correlate with both FLIPI and TMTV and are associated with earlier need for treatment. Serial ctDNA monitoring shows fluctuating levels that correlate with tumor burden on CT which provides a non-invasive method to monitor disease.

RFS of these 8 patients after purine analog monotherapy was also inferior compared to a control group of 34 patients who received cladribine monotherapy and began prospective follow-up before any relapses (19.9 vs 271.8 months, p<0.0001). Non-V600E BRAF mutations were observed in patients with classic HCL immunophenotype, some of which were co-mutations in BRAF with V600E. In view of the inferior RFS in these patients when purine analog was not combined with rituximab, these mutations may constitute a higher risk for relapse or chemoresistance. While those with BRAF V600 mutations might be candidates for BRAF inhibition, those with other BRAF mutations represent an opportunity for development of other specific inhibitors, not only for HCL/HCLv, but also for other malignancies.

Zanubrutinib is a second-generation BTKi with superior PFS and safety compared with ibrutinib (Brown NEJM 2023). Five-year follow up of the BOVen regimen demonstrates frequent uMRD4 in PB (96%) and BM (92%), and uMRD4 was durable with a median MRD4-free survival of 34 mo. Retreatment with zanubrutinib-venetoclax was also well-tolerated and effective. A phase 2 trial of BOVen with ΔMRD400-directed treatment duration is ongoing.

Responses are durable, with 89%, 87%, and 77% 4-yr PFS in all-comer, uIGHV, and TP53 aberrant pts. Our data support further study of AVO for pts with TN high risk CLL in GCLLSG CLL16 and future trials.

VO is highly effective and feasible in both academic and community settings. The ability of obi to debulk patients prior to ven initiation allowed most patients to receive ven initiation in the outpatient setting. TLS is rare and was only seen secondary to obi.

With a 3-year follow-up, epcoritamab continued to show deep and durable responses, with more than half of complete responders remaining in remission at 3 years: median duration of CR, 36.1 mo. Sustained MRD negativity was observed. Long-term safety was consistent with prior reports.

With over 3 years of follow-up, single-agent epcoritamab demonstrated deep and durable responses and manageable side effects in CAR T–naive pts with R/R LBCL, as demonstrated by this subgroup analysis. Results were consistent with those seen in the overall EPCORE NHL-1 LBCL population, considering differences in baseline characteristics, and show that epcoritamab can be administered safely and effectively before or after CAR T for the treatment of R/R LBCL.

Our series reinforces the poor prognosis of advanced stage HGBCL with less intensive regimens such as R-CHOP. In contrast to several other series, MYC/BCL6-R are associated with inferior OS in our cohort, which may be secondary to a higher frequency of CNS relapse despite similar administration of CNS prophylaxis. Indeed, there was no clear impact of CNS prophylaxis/IT-chemotherapy as relapses were distributed equally between those who did or did not receive prophylaxis.