Large B-cell Lymphoma Research Articles

"Misdiagnosis of diffuse large B-cell lymphoma in the maxillary sinus as a dental abscess"

Introduction: Diffuse large B-cell Lymphoma (DLBCL) is a heterogeneous group of malignant tumors with diverse prognoses, histological appearances, and clinical symptoms. While it commonly affects lymphoid tissues, its occurrence in the nasal cavity and paranasal sinuses is rare and poses significant diagnostic challenges. Case presentation: We present a case of a 53-year-old man with a history of testicular non-Hodgkin lymphoma treated five months prior. He presented with symptoms initially misdiagnosed as a dental abscess, which was later identified as DLBCL in the maxillary sinus. Discussion: The etiology of primary lymphoma in the oral region remains unclear. Due to its rarity, specific prognostic factors and optimal treatment strategies are not well-established. This case highlights the diagnostic challenges and underscores the importance of considering lymphoma in the differential diagnosis of non-responsive dental abscesses. Conclusion: This case underscores the importance of thorough investigation in patients with non-responsive dental abscesses. Early identification and appropriate management of DLBCL in uncommon sites require heightened clinical awareness and interdisciplinary collaboration. The optimal treatment approach remains debated and warrants further research.

Treatment patterns, healthcare resource utilization, and costs in Medicare patients with diffuse large B-cell lymphoma: a retrospective claims analysis (2015–2020)

Aims To understand treatment patterns, healthcare resource utilization (HCRU), and the economic burden of diffuse large B-cell lymphoma (DLBCL) in elderly adults in the US. Materials and methods This retrospective database analysis utilized US Centers for Medicare and Medicaid Services Medicare fee-for-service administrative claims data from 2015 to 2020 to describe DLBCL patient characteristics, treatment patterns, HCRU, and costs among patients aged ≥66 years. Patients were indexed at DLBCL diagnosis and required to have continuous enrollment from 12 months pre-index until 3 months post-index. HCRU and costs (USD 2022) are reported as per-patient per-month (PPPM) estimates. Results A total of 11,893 patients received ≥1-line (L) therapy; 1,633 and 391 received ≥2 L and ≥3 L therapies, respectively. Median (Q1, Q3) age at 1 L, 2 L, and 3 L initiation, respectively, was 76 (71, 81), 77 (72, 82), and 77 (72, 82) years. The most common therapy was R-CHOP (70.9%) for 1 L and bendamustine ± rituximab for 2 L (18.7%) and 3 L (17.4%). CAR T was used by 14.8% of patients in 3 L. Overall, 39.6% (1 L), 42.1% (2 L), and 47.8% (3 L) of patients had all-cause hospitalizations. All-cause mean (median [Q1–Q3]) costs PPPM during each line were $22,060 ($20,121 [$16,676–$24,597]) in 1 L, $30,027 ($20,868 [$13,416–$31,016]) in 2 L, and $47,064 ($25,689 [$15,555–$44,149]) in 3 L, with increasing costs driven primarily by inpatient expenses. Total all-cause 3 L mean (median [Q1–Q3]) costs PPPM for patients with and without CAR T were $153,847 ($100,768 [$26,534–$253,630]) and $28,466 ($23,696 [$15,466–$39,107]), respectively. Conclusions No clear standard of care exists in 3 L therapy for older adults with relapsed/refractory DLBCL. The economic burden of DLBCL intensifies with each progressing line of therapy, thus underscoring the need for additional therapeutic options.

Advances in the understanding of molecular genetics and therapy of Richter transformation in chronic lymphocytic leukemia.

Richter's transformation (RT) is defined as the evolution of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. This complication is rare and aggressive, with poor prognosis and dismal survival. Clonal relationship with the underlying CLL/SLL, observed in ∼80% of cases, represents one of the main factors affecting prognosis. Treatment has been historically based on chemoimmunotherapy, but frequent mutations in genes involved in cell survival and proliferation-such as TP53, NOTCH1, MYC, CDKN2A-confer resistance to standard treatments. During the last years, advances in the knowledge of the biological mechanisms underlying RT allowed to identify genetic and molecular lesions that can potentially be targeted by novel selective agents. Pathway and checkpoint inhibitors, bispecific antibodies and CAR T-cell therapy are currently under investigation and represent promising treatment options. This review summarizes current biological evidence and available data on novel therapeutic agents.

Metabolic tumor volume from baseline [18F]FDG PET/CT at diagnosis improves the IPI stratification in patients with diffuse large B-cell lymphoma.

Although several different parameters of PET/CT were reported to be predictive of survival in DLBCL, the best parameter remains to be elucidated and whether it could improve the risk stratification of IPI in patients with DLBCL. 262 DLBCL patients including in the training and validation cohort were retrospectively analyzed in this study. Among different parameters, MTV was identified as the optimal prognostic parameter with a maximum area under the curve (AUC) of 0.652 ± 0.112 than TLG and SDmax (0.645 ± 0.113 and 0.600 ± 0.117, respectively). Patients with high MTV were associated with inferior PFS (p < 0.001 and p = 0.021, respectively) and OS (p < 0.001 and p < 0.001, respectively) in both the training and validation cohort. The multivariate analysis revealed that high MTV was an unfavorable factor for PFS (relative ratio [RR], 2.295; 95% confidence interval [CI], 1.457-3.615; p < 0.01) and OS (RR, 2.929; 95% CI 1.679-5.109; p < 0.01) independent of IPI. Further analysis showed MTV could improve the risk stratification of IPI for both PFS and OS (p < 0.01 and p < 0.01, respectively). In conclusion, our study suggests that MTV was an optimal prognostic parameter of PET/CT for survival and it could improve the risk stratification of IPI in DLBCL, which may help to guide treatment in clinical trial.

Population modeling analyses of crizotinib in pediatric patients with ALK-positive advanced cancers.

Alterations in the ALK (anaplastic lymphoma kinase) gene play a critical role in pathogenesis of anaplastic large cell lymphoma (ALCL). Crizotinib is a small molecule competitive inhibitor of ALK, ROS1, and MET kinases and was approved for pediatric patients with ALK-positive relapsed or refractory, systemic ALCL, and ALK-positive unresectable, recurrent, or refractory inflammatory myofibroblastic tumors (IMT). Crizotinib data from pediatric patients with relapsed or refractory solid tumors, IMT, or ALCL were included in the analyses. All patients received crizotinib orally at doses ranging from 100 to 365mg/m2 twice daily (BID). PopPK analyses were conducted to characterize crizotinib disposition in pediatric patients. Exposure-response (ER) safety and antitumor analyses were conducted to characterize relationships between crizotinib dose or exposure with safety and antitumor activity endpoints of interest. The population pharmacokinetic (popPK), ER safety, and ER antitumor analysis included 98, 110, and 36 pediatric patients, respectively. A one-compartment pharmacokinetic model with allometric scaling, first-order elimination, and first-order absorption with lag time adequately described the data. Natural log-transformed model-predicted crizotinib AUCss (steady-state area under the concentration-time curve) demonstrated a significant, positive relationship with Grade ≥3 NEUTROPENIA and Any Grade VISION DISORDER. Crizotinib dose demonstrated a positive relationship with objective response rate. No significant differences in PK were identified across a wide range of ages or across tumor types, suggesting body surface area (BSA)-based dosing adequately adjusted for differences in patient size to achieve similar systemic crizotinib exposures across young children and adolescent pediatric patients. None of the myelosuppressive events except Grade ≥3 NEUTROPENIA had significant relationships identified with crizotinib dose or exposure, suggesting crizotinib is a tolerable treatment with less hematological toxicity than traditional chemotherapy regimens for pediatric patients with ALK-mutated cancers. Results from the presented analyses support the pediatric dosing recommendations in the product label.

Several factors that predict the outcome of large B-cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T-cell therapy can be identified before cell administration.

The aim of this study was to analyse the outcomes of patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CAR-Tx), with a focus on outcomes after CAR T-cell failure, and to define the risk factors for rapid progression and further treatment. We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd-line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022. The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression-free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty-three patients (59%) were refractory or relapsed after CAR-Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow-up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR-Tx. Risk factors for not receiving further therapy after CAR-Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS-2 (from R/P after CAR-Tx) was 6.7 months (6-month 57.9%) for treated patients and 0.4 months (6-month 4.2%) for untreated patients (p < 0.001). The median PFS-2 (from R/P after CAR-Tx) was 3.2 months (6-month 28.5%) for treated patients. The risk factors for a shorter PFS-2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS-2 for treated patients. Our findings allow better stratification of CAR-Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement).

Real World Data on Efficacy and Safety of EPOCH in T-Cell Lymphoma

BackgroundT-cell lymphomas are a heterogeneous group of lymphoid malignancies with poor outcomes. Frontline multiagent chemotherapy options include CHOP (prednisone, vincristine, cyclophosphamide, and doxorubicin), brentuximab-CHP, CHOEP, and EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin). Patients and MethodsWe report our single institution data for safety and efficacy of EPOCH in 38 patients with aggressive T-cell lymphoma including both peripheral T cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). ResultsEighteen patients received EPOCH as first-line and 21 in the relapsed/refractory (R/R) setting. In 36 evaluable patients, the overall response rate (ORR) was 77% (95% CI, 61%-89%) with 19 (53%) patients achieving complete response (CR) (95% CI, 36%-69%). The ORR in first line and R/R settings were 80% (95% CI, 46%-94%) and 75% (95% CI, 52%-90%), respectively. Response rate was similar in African American versus Caucasian patients but was higher in CD30 negative versus positive patients. Most common grade 3/4 adverse events included cytopenias. ConclusionsOverall, EPOCH was well tolerated with high response rates in first line and R/R setting.

ABCL-081 Epcoritamab as Standard of Care (SOC) for Relapse/Refractory (R/R) Large B-Cell Lymphoma (LBCL)

ABCL-081 Epcoritamab as Standard of Care (SOC) for Relapse/Refractory (R/R) Large B-Cell Lymphoma (LBCL)

IBCL-541 A Comprehensive Single-Cell Multi-Omic Analysis to Depict the Biological Heterogeneity of Follicular and Large B-Cell Lymphomas

IBCL-541 A Comprehensive Single-Cell Multi-Omic Analysis to Depict the Biological Heterogeneity of Follicular and Large B-Cell Lymphomas

Prospective Assessment of Quality of Life and Patient-Reported Toxicities Over the First Year After Chimeric Antigen Receptor T-Cell Therapy

Chimeric antigen receptor (CAR) T-cell therapy has transformed survival outcomes in patients with relapsed and refractory large B-cell lymphoma (LBCL), but it is associated with a variety of side effects. This study examined changes in patient-reported quality of life (QoL) and toxicities, as well as risk factors for worse QoL and toxicities, in the first year after treatment. Patients with LBCL completed questionnaires assessing QoL and toxicity severity before infusion, and 90, 180, and 360 days after infusion. Mixed models were used to examine changes in QoL and toxicities over time, and clinical moderators of change in QoL and toxicities. Patients reported improvements in physical functioning and fatigue in the year after treatment (P values <.01), but there were no changes in pain, anxiety, or depression over time. Patients with active disease at day 90 reported more physical dysfunction at all postinfusion timepoints (Ps ≤ .01) compared to patients who responded to treatment. Similarly, patients with active disease at day 90 reported worsening depression over time, such that at day 360, depressive symptoms were worse for patients with active disease than patients without active disease (P = .02). Patients treated with 4+ lines of prior therapy reported worsening pain and anxiety over time, such that at day 360, both pain and anxiety were significantly worse for patients previously treated with 4 of more lines of therapy than patients treated with fewer lines of therapy (Ps ≤ .01). Regarding toxicities, patients reported decreasing overall toxicity burden up to day 180, with subsequent worsening at day 360 (P = .02). Most patients reported at least one or two grade 2 toxicities at each timepoint. Patients demonstrated unchanging or improved QoL after treatment with CAR T-cell therapy, but active disease and greater prior lines of therapy were associated with worse QoL outcomes over time. Toxicity severity also improved during the first 6 months post-treatment, but worsened thereafter, particularly among patients with active disease after treatment.

ABCL-185 Mosunetuzumab wWth Polatuzumab Vedotin: Subgroup Analyses in Patients (pts) With Primary Refractory or Early Relapsed Large B-Cell Lymphoma (LBCL)

ABCL-185 Mosunetuzumab wWth Polatuzumab Vedotin: Subgroup Analyses in Patients (pts) With Primary Refractory or Early Relapsed Large B-Cell Lymphoma (LBCL)

Characterization of lymphopenia and correlating the risk of cytopenias with dose and BM volume irradiated in aggressive B-cell lymphoma patients bridged with radiation therapy for CAR-T cell therapy

IntroductionThe impact of bridging radiation therapy (bRT) for CAR T-cell therapy on absolute lymphocyte count (ALC) kinetics and treatment outcome is unknown. MethodsWe retrospectively reviewed adults with relapsed/refractory aggressive large B-cell lymphoma (LBCL) who received bRT prior to CD-19 CAR-T between 11/2017-4/2023. The change in ALC (ALC Δ RT) was computed by subtracting ALC pre- and post-bRT. Percent bone marrow (%BM) irradiated was calculated by estimating skeletal BM distribution. PFS, DSS, and OS were modeled via Kaplan-Meier. ResultsFifty-one patients received bRT, of which 13 (25.5%) had bulky disease (≥7.5cm). The median bRT dose was 30Gy (range: 4-48Gy); 26 patients (51%) received ≥30Gy. Thirty-one patients (61%) received bRT comprehensively to all disease sites. The median cumulative %BM irradiated was 5.05% (range: 0-50%). At a median follow-up of 10.3 months (95% CI: 7.7-16.4), the 1-year OS, PFS, and DSS rates were 80% (95% CI: 66-99), 78% (64-87), and 82% (68-90), respectively. The incidence of ≥Grade 3 lymphopenia was 33% pre-RT and 68% post-RT, but recovered to 43% at the conditioning chemotherapy (CC) timepoint. There was no correlation between post-RT Grade ≥3 lymphopenia and the receipt of comprehensive bRT, combined modality bridging, ≥30Gy bRT, or bRT to ≥15% of BM (all p>0.2). Among patients with Grade 0-2 lymphopenia pre-RT, increased conversion to Grade ≥3 lymphopenia post-RT correlated with comprehensive or ≥30Gy bRT, but these factors did not impair ALC recovery at CC. There was no association between ALC Δ RT or post-RT ALC with 30 or 90 day response (p>0.25), DSS, PFS, or OS (p>0.3). ConclusionsLymphocyte change during bRT is not associated with CAR-T outcomes. Persistent cytopenia risk following bRT is not associated with bRT to ≥30Gy, ≥15% of BM, or comprehensive coverage. While bRT can be delivered safely, we urge careful treatment planning when incorporating into pre-CAR-T regimens.

Standardization of CD30 immunohistochemistry staining among three automated immunostaining platforms.

The identification of CD30 expression by immunohistochemistry is essential for the treatment of lymphomas using an antibody-drug conjugate targeting CD30. However, no standardized protocol for CD30 staining has been available. In this study, we compared three common automated immunostaining platforms {Bond III (B III), Dako Omnis (DO) and Ventana BenchMark ULTRA (VBMU)}. A primary antibody for CD30, the Ber-H2 clone, was diluted 50- to 400-fold for B III and DO, and ready-to-use antibody was used for VBMU. An enhancement step using a linker was introduced in all protocols. First, several candidate dilutions were selected for each platform by staining six cases. These candidate conditions were then confirmed with 60 cases of various types of peripheral T-cell lymphomas (PTCLs). The concordance rates of CD30 expression among platforms differed depending on cutoff values and antibody dilutions, except for anaplastic large cell lymphoma. The concordance rates among three platforms in the evaluation of "positive" or "negative" were 100% and 97% when the cutoff values were 1% and 10% respectively, if using 400-diluted antibody in B III and 100-diluted antibody in DO. This study demonstrated the feasibility of equalizing CD30 staining of PTCLs among different platforms by adjusting protocols.

Registry of Genetic Alterations of Taiwan Non-Small Cell Lung Cancer by Comprehensive Next-Generation Sequencing: A Real-World Cohort Study-Taiwan Cooperative Oncology Group T1521.

Tissue-based next-generation sequencing (NGS) analysis is highly recommended for patients with advanced/metastatic non-small cell lung cancer (NSCLC). We investigated a specific patient population with NSCLC that required tissue-based NGS analysis. We enrolled 500 patients with advanced/metastatic (1) epidermal growth factor receptor (EGFR) mutations or anaplastic large-cell lymphoma kinase (ALK) rearrangement-positive NSCLC who had failed at minimum one line of tyrosine kinase inhibitor (TKI) therapy, (2) EGFR-/ALK-negative nonsquamous, and (3) non- or light-smoker patients with squamous NSCLC who were treatment-naïve or had failed at maximum two lines of systemic treatment. These patients were divided into five cohorts. Comprehensive tissue-based NGS testing (ACTOnco+) was conducted. Cohort 1: EGFR TKI-pretreated EGFR-mutated population (50.0%, n = 250), cohort 2: ALK inhibitor-pretreated ALK-positive population (1.6%, n = 8), cohort 3: treatment-naïve EGFR-/ALK-negative population (28.2%, n = 141), cohort 4: pretreated EGFR-/ALK-negative population (16.8%, n = 84), and cohort 5: squamous cell carcinoma (3.4%, n = 17). In cohort 1, 11.2% (28/250) of the patients had MET amplification, 32.4% (81/250) had been treated with osimertinib, and EGFR C797S was detected in 6.2% (5/81) of these patients. In cohort 2, resistance ALK mutation was detected in 37.5% (3/8) of the patients. In cohorts 3 and 4, targetable genetic alterations, including EGFR mutation (13.3%), ERBB2 mutation (9.3%), MET exon 14 skipping (5.3%), KRAS G12C mutation (4.4%), ROS1 fusion (2.7%), RET fusion (1.8%), and BRAF V600E mutation (1.3%), were detected. In cohort 5, MET exon 14 skipping was detected in 29.4% (5/17) of the patients. This multicenter registration study investigated tissue-based NGS for a specific patient population with NSCLC in Taiwan.

Pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor in patients with B-cell malignancies: analysis of the Richter transformation subgroup from the multicentre, open-label, phase 1/2 BRUIN study

Richter transformation usually presents as an aggressive diffuse large B-cell lymphoma, occurs in up to 10% of patients with chronic lymphocytic leukaemia, has no approved therapies, and is associated with a poor prognosis. Pirtobrutinib has shown promising efficacy and tolerability in patients with relapsed or refractory B-cell malignancies, including those who progress on covalent Bruton tyrosine kinase (BTK) inhibitors. This study aims to report the safety and activity of pirtobrutinib monotherapy in a subgroup of patients with Richter transformation from the multicentre, open-label, phase 1/2 BRUIN study. This analysis included adult patients (aged ≥18 years) with histologically confirmed Richter transformation, an Eastern Cooperative Oncology Group performance status score of 0-2, and no limit of previous therapies, with patients receiving first-line treatment added in a protocol amendment (version 9.0, Dec 15, 2021). Pirtobrutinib 200 mg was administered orally once a day in 28-day cycles. The primary endpoint of phase 1 of the BRUIN trial as a whole, which has been previously reported, was to establish the recommended phase 2 dose for pirtobrutinib monotherapy and the phase 2 primary endpoint was overall response rate. Safety and activity were measured in all patients who received at least one dose of pirtobrutinib monotherapy. This BRUIN phase 1/2 trial was registered with ClinicalTrials.gov and is closed to enrolment (NCT03740529). Between Dec 26, 2019, and July 22, 2022, 82 patients were enrolled, of whom five were enrolled during phase 1 and 77 during phase 2. All but one patient received a starting dose of 200 mg pirtobrutinib once a day as the recommended phase 2 dose. The remaining patient received 150 mg pirtobrutinib once a day, which was not escalated to 200 mg. The median age of patients was 67 years (IQR 59-72). 55 (67%) of 82 patients were male and 27 (33%) were female. Most patients were White (65 [79%] of 82). 74 (90%) of 82 patients received at least one previous Richter transformation-directed therapy. Most patients (61 [74%] of 82) had received previous covalent BTK inhibitor therapy for chronic lymphocytic leukaemia or Richter transformation. The overall response rate was 50·0% (95% CI 38·7-61·3). 11 (13%) of 82 patients had a complete response and 30 (37%) of 82 patients had a partial response. Eight patients with ongoing response electively discontinued pirtobrutinib to undergo stem-cell transplantation. The most common grade 3 or worse adverse event was neutropenia (n=19). There were no treatment-related deaths. Pirtobrutinib shows promising safety and activity among patients with Richter transformation, most of whom received previous Richter transformation-directed therapy, including covalent BTK inhibitors. These data suggest that further investigation is warranted of pirtobrutinib as a treatment option for patients with relapsed or refractory Richter transformation after treatment with a covalent BTK inhibitor. Loxo Oncology.

819P Efficacy and safety of orelabrutinib plus R-CHOP-like regimens for treatment-naïve diffuse large B-cell lymphoma with double expression

819P Efficacy and safety of orelabrutinib plus R-CHOP-like regimens for treatment-naïve diffuse large B-cell lymphoma with double expression

Specific Mutation Predict Relapse/Refractory Diffuse Large B-Cell Lymphoma.

The application of rituximab has significantly enhanced the overall survival rates in patients with diffuse large B-cell lymphoma (DLBCL). Regrettably, a significant number of patients still progress to relapse/refractory DLBCL (rrDLBCL). Herein, we employed targeted sequencing of 55 genes to investigate if gene mutations could predict the progression to rrDLBCL. Additionally, we compared the mutation profiles at the time of DLBCL diagnosis with those found in rrDLBCL cases. Our findings highlighted significantly elevated mutation frequencies of TP53, MEF2B and CD58 in diagnostic biopsies from patients who progressed to relapse or refractory disease, with CD58 mutations exclusively observed in the rrDLBCL group. In assessing the predictive power of mutation profiles for treatment responses in primary DLBCL patients, we found that the frequency of CARD11 mutations was substantially higher in non-response group as compared with those who responded to immunochemotherapy. In addition, we revealed mutations in HIST2H2AB, BCL2, NRXN3, FOXO1, HIST1H1C, LYN and TBL1XR1 genes were only detected in initial diagnostic biopsies, mutations in the EBF1 gene were solely detected in the rrDLBCL patients. Collectively, this study elucidates some of the genetic mechanisms contributing to the progression of rrDLBCL and suggests that the presence of CD58 mutations might serve as a powerful predictive marker for relapse/refractory outcomes in primary DLBCL patients.

MicroRNAs implicated in canine diffuse large B-cell lymphoma prognosis.

Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin lymphoma (NHL) in domestic dogs, with many similarities to its human counterpart. The progression of the disease is rapid, and treatment must be initiated early to achieve cancer remission and extend life. This study examined the relationship between progression-free survival (PFS) and microRNA (miRNA) expression in dogs with DLBCL. miRNAs are small non-coding RNA molecules that typically regulate gene expression post-transcriptionally. They are involved in several pathophysiological processes, including the growth and progression of cancer. Based on the analysis of small RNA sequencing (sRNA-seq) data, we validated a group of miRNAs in lymph nodes from 44 DLBCL-affected dogs with known outcomes. We used quantitative PCR to quantify their expression and report a specific subset of miRNAs is associated with decreased PFS in dogs with DLBCL. The miR-192-5p and miR-16-5p expression were significantly downregulated in dogs with increased PFS. These results indicate that miRNA profiling may potentially identify dogs with DLBCL that will experience poor outcomes following treatment. Identifying specific miRNAs that correlate with the progression of canine DLBCL could aid the development of individualized treatment regimens for dogs.

844TiP Orelabrutinib combined with rituximab for the treatment of elderly patients with newly diagnosed non-GCB diffuse large B-cell lymphoma (DLBCL) under the guidance of genetic subtype: A prospective, multicenter, single-arm, response-adaptive clinical study (Origin)

844TiP Orelabrutinib combined with rituximab for the treatment of elderly patients with newly diagnosed non-GCB diffuse large B-cell lymphoma (DLBCL) under the guidance of genetic subtype: A prospective, multicenter, single-arm, response-adaptive clinical study (Origin)

Utility of PD-1, PD-L1, and IDO-1 Stains in Ocular Extranodal Marginal Zone Lymphoma (MZL) and Diffuse Large B-cell Lymphoma (DLBCL).

Extranodal marginal zone lymphoma (EMZL) is the most common subtype of ocular lymphomas. Diffuse large B-cell lymphoma (DLBCL) and EMZL with large-cell transformation present diagnostic challenges. Radiotherapy is the standard treatment for ocular lymphomas, but complications and relapse are common. Diagnostic utility in challenging cases, as well as treatment options using immune checkpoint inhibitors, are unclear in ocular lymphomas. We herein investigated the PD-1, PD-L1, and IDO1 staining patterns in 20 cases of ocular lymphomas, including EMZL (n=14), EMZL with increased large cells (n=2), and DLBCL (n=4). PD-1, PD-L1, and IDO1 staining was not detected in lymphoma cells in any cases but was observed within the tumor microenvironment in all cases. Positivity for PD-1, PD-L1, and IDO1 in inflammatory cells was seen either intratumorally or peritumorally. In all 6 cases with significantly more large B cells, the density of PD-1, PD-L1, and IDO1 expression in the tumor microenvironment was higher than that of the remaining 14 cases without large B cells ( P -value<0.0001), whereas other clinicopathologic features showed no statistical correlation. Increased expression of PD-1, PD-L1, and IDO1 in the inflammatory milieu in cases with large cells may provide diagnostic utility in small biopsies as well as therapeutic potential.