INTRODUCTION:Performance status assessments may overlook important health vulnerabilities in adults with cancer. While geriatric assessment (GA) systematically evaluates multiple domains including physical function, cognition, psychological health, comorbidity, and nutrition, it has been predominantly studied in older adults. We evaluated the prevalence and patterns of GA-identified deficits among adults of all ages initiating systemic therapy for lymphoma. MATERIALS AND METHODS:Adults with lymphoma enrolled in a prospective registry at an academic cancer center from 2018 to 2025 completed a modified Cancer and Aging Research Group (CARG) GA at treatment initiation. The assessment included validated measures across eight domains: mobility (Timed Up and Go), falls history, instrumental activities of daily living (IADLs), medication burden, comorbidities, weight loss, cognition (Blessed Orientation-Memory-Concentration test), and psychological health (Mental Health Index-13). Karnofsky Performance Status (KPS) was documented. Prevalence of deficits was compared between adults <65 and ≥ 65 years. RESULTS:Among 97 participants (mean age 57 years, range 22-84; 39% ≥65 years), 94% had normal KPS (≥80). Despite preserved performance status, 56% had multiple (≥2) GA-identified deficits, and only 21% had zero deficits. The most common deficit was unintentional weight loss (43% overall). Among younger adults (<65 years), substantial proportions reported weight loss (34%), falls (27%), IADL impairment (27%), and anxiety or depression (45%). Most deficits did not differ significantly between age groups, though weight loss, multimorbidity (≥4 comorbidities), and severe polypharmacy (≥10 medications) were more prevalent in older adults. DISCUSSION:GA reveals high prevalence of health-related deficits across multiple domains in adults with lymphoma regardless of age, despite preserved performance status. These findings support a shift toward needs-based rather than age-based approaches to identify individuals who may benefit from supportive care interventions.

7001 Background: Human immunodeficiency virus (HIV)-related diffuse large B-cell lymphomas (DLBCL) are heterogeneous in nature, clinically, & molecularly. R-da-EPOCH is accepted as a standard of care in HIV+DLBCL. Classifying tumors with respect to immunophenotype & genomic features may facilitate personalized therapy to improve outcomes in this diverse disease. The Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib (ibr), also inhibits inducible T cell kinase (ITK). As HIV hijacks host ITK during replication, ibr may have additional clinical benefits in HIV+DLBCL. This trial added ibr to R-da-EPOCH in HIV+DLBCL, with an attempt to enrich for non-germinal center B-cell (non-GCB) subtype, to evaluate safety, feasibility & activity, impact on T cells, & correlate lymphoma cell of origin (COO) with response. Methods: This multi-center study included a 3+3 dose de-escalation cohort followed by dose-expansion at recommended phase 2 dose (RP2D). Participants (pts) age 18-64 years (y) with stage II-IV HIV-DLBCL were untreated or received 1 cycle (cy) R-da-EPOCH/CHOP off-study. CD4 <100 & asymptomatic leptomeningeal disease were allowed. Ibr was dosed daily days 1-21 & R-da-EPOCH administered as previously published (PMID 32430507) for 6 total cy. Moderate/strong CYP3A4 inhibitors were excluded, due to effects on ibr and chemotherapy. Results: 43 pts were evaluable for toxicity & 37 evaluable for response. 41/43 (95%) pts tolerated ≥2 cy; median cy of study therapy (tx) received = 5. At baseline median age was 52y (24-64) & CD4 count 204 (21-757); 9 pts had CD4 <100. 81% were male, 42% White & 49% Black. 86% were stage III/IV, 40% non-GCB, & 88% had ECOG 0-1. Ibr RP2D was 560mg daily. Noting PET was optional, overall response rate was 100% with 57% (21/37) complete (CR) & 43% (16/37) partial responses (PR). Relapse/progression occurred in 16% (6/37; 1CR, 5PR) during a median follow-up of 4.2y (95%CI = 2.3 to 4.87); median duration of response = 2.8y. 3y event-free (EFS) & overall survival (OS) were 83 & 81% respectively (GCB: 88 & 87%, non-GCB: 76 & 63%). Among 679 treatment-related adverse events (TRAE), the most frequent were (total, % grade (gr) 3+) anemia (105, 50%), thrombocytopenia (81, 41%), neutropenia (60, 88%) & lymphopenia (60, 68%). Non-hematologic AEs (total TRAE, # max gr) included diarrhea (22, 2 gr3), nausea (21, 1 g3), hypokalemia (20, 4 gr3), fatigue (17, 17 gr1), & sepsis (1 gr4). Reasons for tx discontinuation: 1 progression, 4 withdrawal, 4 TRAE, 1 lost to follow up. Conclusions: Incorporating ibrutinib 560mg daily with R-da-EPOCH in HIV-related DLBCL treatment resulted in manageable toxicities typical of R-da-EPOCH. Although lower confirmed CR, 3y EFS & OS are comparable or higher than prior studies of HIV+DLBCL R-da-EPOCH. Ongoing studies to be updated at the meeting include impact on T cell subsets, & correlations of response & survival with circulating tumor DNA & lymphoma features (EBV, MYC, BCL2, BCL6 & genomic determinations of COO). Clinical trial information: NCI-2017-01240 .

Plasmablastic lymphoma (PBL) is a rare, aggressive AIDS-related lymphoma observed in patients with immunosuppressed states as well as in immunocompetent individuals. We sought to determine survival outcomes, prognostic factors, and optimal treatment regimens in a large, contemporary cohort of patients with PBL in the United States. We performed a multicenter, retrospective cohort study, including 344 patients diagnosed with PBL between 2005 and 2022. Patients were stratified into cohorts according to underlying immune status. Survival outcomes were calculated using Kaplan-Meier statistics, with cohort-specific survival outcomes adjusted using propensity score-based weighting. Factors associated with outcomes were assessed via multivariable models using multiple imputation. The median age at diagnosis was 53 years, most patients were male (n = 270), and many had HIV (n = 164). The median OS was 5.0 years, with a median PFS of 1.4 years. Patients living with HIV had the best outcomes, whereas patients with prior organ transplantation had the worst outcomes. Use of higher intensity chemotherapy regimens and use of a proteasome inhibitor in the frontline setting did not show survival benefit. While there was no clear optimal treatment approach in the frontline setting, the median OS of 5.0 years is dramatically improved compared with historical controls.

346 Background: Findings from a comprehensive functional assessment (CA) in a cohort of adults with Hodgkin and non-Hodgkin lymphoma (NHL). Specifically, we evaluate the utility of the CA in identifying functional, cognitive, and other patient-reported characteristics prior to chemotherapy. Methods: Adults aged 18 and older with lymphoma including Hodgkin, aggressive B-cell NHL, indolent B-cell NHL (including CLL/SLL), or T-cell NHL were recruited to a prospective observational cohort study from 2018 through 2025 when starting a new line of therapy for either newly diagnosed or relapsed/refractory lymphoma. Study participants completed a CA based on a modified Cancer and Aging Research Group geriatric assessment (Hurria et al, Cancer 2025; mycarg.org/?page_id=4480). Initial assessments and questionnaires were performed at time of enrollment. Data were analyzed using descriptive statistics for the full cohort and stratified by concurrent Karnofsky performance status (KPS) (score < 80 vs ≥ 80). The domains assessed by CA included number of medications taken daily, number of comorbidities, dependence in instrumental activities of daily living (IADLs), Timed Up & Go (TUG), number of falls in the preceding 6 months, and presence of depression or anxiety via Mental Health Index-13. Results: Among 80 adults, the mean age was 57 years (range 22-84), 24% were aged ≥65 years, and 83% were white. 25% of the cohort had Hodgkin lymphoma, 46% had an aggressive B-cell NHL, 18% indolent B-cell NHL, and the remainder had T-cell NHL. In the full cohort, dependence in ≥1 instrumental activity of daily living was the most common area of impairment, observed in 31%, followed by ≥1 fall in the prior 6 months among 25% of the cohort (Table). The average number of medications and comorbidities per patient was 5 and 1.3, respectively. Although most of the cohort (91%) had a normal performance status (KPS ≥ 80), a majority of the cohort (51%) had multiple impairments identified on the CA, with a plurality (34%) having ≥ 3 impairments. Only 23% of the cohort had zero deficits identified. Conclusions: A modified CARG geriatric assessment demonstrated functional impairments even in patients considered to have a good performance status based on a KPS (≥ 80) and younger patients that would not be typically defined as “geriatric”. Future studies should focus on using CA measures to identify opportunities for targeting relevant supportive care interventions to patients. Considering the relatively young median age observed in this cohort, the current study highlights the potential utility for comprehensive assessment tools derived from the geriatrics literature to identify clinically relevant issues among younger as well as older adults with cancer. Domain Polypharmacy (>10) High Comorbidity (4+) IADL TUG Falls Weight Loss Mental Health Deficit Cognitive Impairment % of cohort 14 8 31 4 25 45 35 10

This article reviews recent clinical updates and research on the evaluation and management of patients with peripheral neuropathy in association with monoclonal gammopathies. Recent studies have elucidated pathogenic mechanisms of IgM paraprotein associated neuropathies, including nodal and paranodal targets and complement mediated processes, suggesting novel therapeutic targets. New chemotherapeutic regimens have improved outcomes and neurotoxic side effect profiles in the treatment of patients with light chain (AL) amyloidosis and POEMS syndrome. Establishing when a monoclonal gammopathy is causative of a peripheral neuropathy remains a clinical challenge. New therapeutic drugs for treatment of IgM paraprotein associated neuropathies show promise. Identifying AL amyloidosis and POEMS early in patients presenting with neuropathy are important. Clinical phenotyping and antibody testing are critical to evaluating patients with paraproteins and peripheral neuropathy.

Introduction: Aggressive adult T-cell leukemia/lymphoma (ATLL) is a type of non-Hodgkin lymphoma that is often fatal. ATLL is exceedingly rare in the United States (US), with most cases occurring in emigrants from human T-lymphotropic virus type 1 (HTLV-1) endemic regions. Studies focusing on ATLL in the US are sparse, and have shown poor response rates; because of this, there is no standard of care treatment approach. Brentuximab vedotin (BV) is a CD30 targeting antibody-drug conjugate that is effective in treating many types of lymphoma, including CD30+ peripheral T-cell lymphomas. Studies have shown efficacy even in lymphomas with very low CD30 expression. We developed a prospective, multicenter pilot study evaluating BV in combination with cyclophosphamide, doxorubicin, etoposide, and prednisone (BV-CHEP) for the treatment of ATLL. We report the final safety and efficacy analysis below. Methods: Adult patients (pts) from 5 centers were enrolled from October 2017 through June 2022. Newly diagnosed ATLL pts were eligible, including the acute, lymphomatous and chronic unfavorable subtypes. Pts did not have to express CD30 to be enrolled; pts were considered CD30+ if there was >1% expression. Frontline consolidation with allogeneic stem cell transplant (alloSCT) was permitted at any time after 2 cycles of BV-CHEP. Transplant-ineligible pts completed a total of 6 cycles of BV-CHEP and those who expressed CD30 were eligible for BV maintenance. Pts could receive prephase steroids and/or 1 cycle of CHOP-equivalent chemotherapy prior to enrollment. Prior antiviral therapy was allowed. Pts were treated with standard dosing every 21 days: BV 1.8 mg/kg on day 1, cyclophosphamide 750 mg/m2 on day 1, doxorubicin 50 mg/m2 on day 1, etoposide 100 mg/m2 days 1-3, and prednisone 100mg days 1-5. All pts received GCSF support. The primary endpoint was CR by PET-CT (and peripheral blood for leukemic types) after at least 2 cycles of therapy per adapted Lugano and ATLL criteria. Secondary endpoints were safety, overall response rate (ORR), progression free survival (PFS) and overall survival (OS). Results: 16 pts were enrolled and evaluable for the safety and efficacy analysis. All pts were HTLV-1 positive. Seven of 16 were the acute type, 8 were lymphomatous, and 1 was chronic unfavorable. Seven of 16 (43.75%) expressed CD30. The median age was 56 (range 34 to 69) and 12 of 16 (75%) were female. 14 of 16 pts identified as Black, 1 identified as Asian, and 1 was other. Countries of origin included: Antigua and Barbuda N=1, Colombia N=1, Haiti N=7, Jamaica N=2, Japan N=1, Liberia N=1, and the US N=3. All pts were advanced stage (12 of 16 stage IV; 4 stage III). Four had positive cerebrospinal fluid at baseline, which cleared with intrathecal (IT) treatments, and 10 were given IT prophylaxis. Nine pts had an ATL-PI score >3 (56.25%) with a median score of 3 (range 2-4). No subjects received prior antiretroviral therapy. 12 of 16 pts completed at least 4 cycles of treatment (median 4.5 cycles; range 2 to 6). Ten of 16 pts achieved a CR (62.5%) and 4 pts achieved a PR (ORR of 87.5%) after >2 cycles of BV-CHEP. The median duration of follow-up was 47.2 mo. The median PFS (mPFS) was 7.11 mo (3.93 to NR) and the median OS (mOS) was 12.2 mo (9.29 to NR) (Fig.1). Of pts who achieved a CR, the mPFS was 11.07 mo and the mOS was 15.7 mo. There was no significant difference in PFS or OS by CD30 status or by ATLL subtype. One pt received 3 cycles of maintenance BV. 5 pts received alloSCT consolidation and there was an OS benefit for this group ( p=0.007; Fig.2). Grade 3 or higher toxicities included neutropenia (N=13), anemia (N=11), thrombocytopenia (N=9), febrile neutropenia (N=7), mucositis (N=6), colitis (N=3), infections (N=3; COVID19, thrush, clostridium difficile), hyponatremia (N=3), and vomiting (N=2). Nine of 16 patients had peripheral neuropathy (all grade 1/2). There were 11 pt deaths, 9 of which were disease-related and 2 were due to shock (hypovolemic and septic) off-treatment. No patients had to come off study due to toxicity and there were no treatment-related deaths. Conclusions: In this final analysis, BV-CHEP was safe and effective for the treatment of aggressive ATLL. High ORR and CR rates were achieved regardless of CD30 status, and compare favorably to prior clinical trials. AlloSCT had an OS benefit with 4 of 5 pts achieving long-term remission. Toxicity was manageable and cytopenias were expected. Peripheral neuropathy was common, but low-grade.

Background: Chimeric antigen receptor T cells targeting CD30 (CD30.CAR) are safe and with promising efficacy when preceded by lymphodepleting chemotherapy. Methods: In a phase 1 dose-escalation study, we assessed the safety of CD30.CAR-T cell infusion as consolidation after carmustine, etoposide, cytarabine, and melphalan (BEAM) autologous stem cell transplant (ASCT) in adult and pediatric patients with high risk relapsed/refractory classical Hodgkin lymphoma (HL) and CD30+ non-Hodgkin lymphoma (NHL). Patients received autologous CD30.CAR-T cells after trilineage hematopoietic engraftment defined as absolute neutrophil count ≥500/mm3 for 3 days, platelets ≥25x109/L and hemoglobin ≥ 8 g/dL without transfusion for 5 days. Findings:T wenty-one patients were enrolled and 18 patients (11 HL, 6 T cell lymphoma, 1 grey zone lymphoma) were infused with CD30.CAR-T cells at a median of 21.5 days (range 17-44 days) after ASCT. There were no dose limiting toxicities from the CAR-T cell product. One patient had grade 1 cytokine release syndrome. At a median follow up of 48 months post infusion, the median progression free survival (PFS) for all patients is 31.5 months and the median PFS for HL patients has not been reached. The 2-year PFS for HL patients was 73%. The median overall survival for all patients has not been reached. CD30.CAR-T cell expansion and persistence in the peripheral blood were similar across CAR-T cell dose levels and comparable to that previously observed in patients post lymphodepleting chemotherapy. Interpretation: CD30.CAR-T cell infusion as consolidation after BEAM ASCT has low rates of toxicity and encouraging efficacy in HL patients at high risk of relapse. Funding: This work was supported by an NHLBI-R01HL114564 and University Cancer Research Fund at the Lineberger Comprehensive Cancer Center. NSG was supported by Lymphoma Research Foundation Career Development Award.Declaration of Interest: The University of North Carolina (UNC) has a research collaboration with Tessa Therapeutics. Competing interests of authors from UNC (GP, JSS, BS) are managed in accordance with institutional policies. This study was monitored by an independent Data Safety Monitoring Committee. NSG has served on an advisory board or consulted for Novartis, Kite, Seagen, ADC Therapeutics, and Caribou Biosciences. MLR is employed by Iqvia Biotech. WAW has done consulting for Teladoc, has been on advisory board for Koneksa Health and Quantum Health, has research funding from Pfizer and Genentech and salary support from the ASH Research Collaborative.Ethical Approval: This study was conducted in accordance with the Declaration of Helsinki and International Conference on Harmonization Guidelines for Good Clinical Practice (CT.gov #NCT02663297) and was approved by the institutional review board at UNC. All patients or parents/legal guardians provided written informed consent.

Background: Adult T-cell Leukemia Lymphoma (ATLL) is a highly aggressive, T-lymphocyte malignancy etiologically linked to the Human T-cell Lymphotropic Virus Type 1 (HTLV-1) infection with a dismal prognosis. Advances to frontline management have afforded better disease control, and multi-agent chemotherapy regimens followed by consolidative allogeneic transplant presents a potential path to cure. Many patients cannot proceed to transplant due to limited donor availability, primary refractory disease, sociocultural barriers, and significant comorbidities. Without transplant, relapse occurs and is characterized by highly chemo-refractory and lethal disease course, with median survival limited to 4-6 months. ATLL impacts the global population with heterogeneous clinical manifestations and variable therapeutic response amongst clinical and geographical subtypes. No standard regimen has been established for treatment of relapsed or refractory (r/r) ATLL, and no FDA approved targeted treatment for relapsed disease exists. Response to salvage chemotherapy is unsatisfactory. There is minimal data on outcomes with national and societal guideline-recommended targeted agents within the US ATLL population. Additionally, guideline-recommended targeted agents for r/r ATLL are extrapolated from international populations representing differing ATLL subtypes and disease biology. There is little data or knowledge of outcomes in non-study populations to support treatment decisions in the relapsed/refractory setting. Mogamulizumab, a humanized monoclonal antibody that exploits C-C chemokine receptor type 4 (CCR4) overexpression of ATLL tumor cells and Treg cells via antibody dependent cellular cytotoxicity (ADCC), demonstrated improved survival in r/r ATLL in an initial Japanese study with variable outcomes in a larger international multi-center trial. Lenalidomide exerts pleiotropic immunomodulatory effects and has a potential synergistic role by augmenting NK cell activity and number. Mogamulizumab and lenalidomide each have demonstrable activity in r/r ATLL but are insufficient as monotherapies. Approach to r/r ATLL remains an unanswered and important question. We describe our experience with mogamulizumab +/- lenalidomide in the r/r ATLL setting. Methods: A retrospective chart review of patients with r/r ATLL treated with mogamulizumab at Boston Medical between January 2018 and January 2024 was conducted. Five patients (5) currently included at time of abstract. Results: All patients had acute r/r ATLL with stage IV disease; 1 patient with leptomeningeal involvement. Median age was 65 (range 30-69), 4 of 5 were female, and all were Afro-Caribbean. All patients received BV-CHEP in the frontline setting, with ≥1 cycle of intrathecal methotrexate. Prior to relapse, 3 of 5 patients achieved a complete response with frontline treatment, 1 had progressive disease, and 1 had a partial response. No patients were able to proceed to consolidative transplant following frontline therapy due to either lack of available donor, primary refractory disease, or medical comorbidities and complications with conditioning. Patients had relapsed disease within an average of 3.15 months (median 1.47 months), (range 23 days - 10.40 months) of initial treatment. At relapse, all patients received mogamulizumab +/- lenalidomide. Median overall survival upon initiating mogamulizumab was 9.9 months (range 2.9 - NR). Toxicities included fatigue, Grade 2 and 3 infections, Grade 2 rash, and 1 instance of Grade 3 peripheral eosinophilia. Conclusions: In this retrospective study of patients with r/r ATLL, mogamulizumab demonstrated effective disease control even in aggressive, primary chemotherapy refractory disease. Mogamulizumab in combination with lenalidomide was generally well tolerated, achieving disease control for up to one year, and importantly offering CNS activity. There were no treatment-related toxicities that required its discontinuation. Our study provides support for a prospective study for the combination regimen.

Introduction: Plasmablastic lymphoma (PBL) is a rare subtype of large B-cell lymphoma first described in 1997 in a small cohort of persons living with HIV (HIV-PBL). Since then, it has been observed post-transplant (PTLD-PBL) and even in otherwise immunocompetent patients (IC-PBL). With no current well-defined standard of care, prognosis of PBL has historically been poor (median overall survival (OS) 7-15 months), although recent studies suggest modest improvements in survival. We aimed to better characterize disease characteristics, treatment patterns, and factors associated with outcomes in a large contemporary US cohort. Methods: Patients (pts) ≥ 18 years old with PBL diagnosed between 1/2005 and 12/2022 from 20 academic centers in the United States were identified. Data on pt and disease characteristics and treatment were collected from medical records. OS, progression-free survival (PFS), lymphoma-specific survival (LSS), treatment-related mortality (TRM), and non-relapse mortality (NRM) were calculated using the Kaplan-Meier method. Cox regression and Fine-Gray competing risk regression were used to assess the association between clinical factors and survival outcomes. Results: 331 pts with PBL were identified. The median age at diagnosis was 53 years (range 20-91y). 78% were male (n = 257). 46% had HIV-PBL (n = 151), 35% had IC-PBL (n = 117), 6% had PTLD-PBL (n = 20), and 13% had PBL with other immunosuppressed states (n = 43). 66% of pts were White (n = 219), 18% were Black/African American (n = 58), and 31% were Hispanic (n = 104). 74% of Black/African American and 52% of Hispanic pts were diagnosed with HIV-PBL, compared with only 37% of White pts. The median age at diagnosis was greater in the IC-PBL group (68y) than in the HIV-PBL and PTLD-PBL groups (46y and 55y, respectively; p < 0.001). Most pts presented with Stage IV disease (61%, n = 220). Bone marrow (BM) involvement was present in 22% (n = 73). 92% of pts had extranodal sites involved at presentation (n = 302), most commonly the GI tract, BM, and oral cavity/jaw. Most tumors were CD138+, CD20-, MYC+, and EBV+ by either EBER or LMP1. EBV positivity was observed in 74% and 81% of PTLD-PBL and HIV-PBL cases, respectively, versus only 50% of IC-PBL cases (p < 0.001). Of the 298 pts who received chemotherapy, the most common first line regimen used was DA-EPOCH (70%), followed by CHOP/CHOP-like regimens (14%), hyper-CVAD (4%), and CODOX-M/IVAC (4%). As part of their initial treatment, 35% of pts received a proteasome inhibitor (n = 104), 20% received rituximab (n = 58), and 3% received daratumumab (n = 10). 35% received CNS prophylaxis with either IT MTX/AraC or HD MTX (n = 103), 19% received radiation in the first line setting (n = 56), and 8% underwent a consolidative autologous HCT in first remission (n = 24). Median FU for the entire cohort was 1.8y (range 0-17y). Median OS was 4.5y, with a median PFS of 1.4y. Median OS was 6.1y for HIV-PBL, 4.1y for IC-PBL, and 1.1y for PTLD-PBL. Factors associated with poor OS and PFS on multivariable analysis (MVA) included advanced age, stage III+, BM involvement, and EBV negativity. Female sex was associated with worse OS on MVA (HR 1.70, p = 0.027) and worse PFS on univariate analysis (HR = 1.53, p = 0.009). Use of CNS prophylaxis was associated with improved OS (HR 0.59, p = 0.031) and PFS on MVA (HR 0.68, p = 0.035). We found no significant difference in OS, PFS, and LSS for pts treated with DA-EPOCH versus pts treated with CHOP. On MVA, DA-EPOCH had a higher TRM compared to CHOP (p < 0.001). The addition of a proteasome inhibitor to 1L chemotherapy did not have a significant impact on OS, PFS, and LSS. While use of radiation and AHCT consolidation were associated with better PFS, OS was unaffected. Conclusion: In this largest US cohort of PBL patients to date, we observed improved outcomes compared to previous studies with 1- and 2y OS rates of 69% and 58%, respectively. Factors associated with worse prognosis were advanced age and stage, BM involvement, and EBV negativity, while HIV status was not associated with survival, consistent with other studies. Also, the absence of an OS benefit with DA-EPOCH and HCT with added toxicity is consistent with findings from other cohorts. We report several novel findings, including worse survival in female patients. More detailed analyses of the impact of immune status, CNS prophylaxis, and second line therapies on outcomes are pending.

BackgroundDespite a higher risk of classical Hodgkin lymphoma (cHL) in people with HIV and the demonstrated safety and efficacy of PD-1 blockade in cHL, there are limited data on the use of these agents in HIV-associated cHL (HIV-cHL).Patients/MethodsWe retrospectively identified patients with HIV-cHL from the “Cancer Therapy using Checkpoint inhibitors in People with HIV-International (CATCH-IT)” database who received nivolumab or pembrolizumab, alone or in combination with other agents, and reviewed records for demographics, disease characteristics, immune-mediated adverse events (imAEs), and treatment outcomes. Changes in CD4+ T-cell counts with treatment were measured via Wilcoxon signed-rank tests. Overall response rate (ORR) was defined as the proportion of patients with partial or complete response (PR/CR) per 2014 Lugano classification.ResultsWe identified 23 patients with HIV-cHL who received a median of 6 cycles of PD-1 blockade: 1 as 1st-line, 6 as 2nd-line, and 16 as ≥3rd-line therapy. Seventeen (74%) patients received monotherapy, 5 (22%) received nivolumab plus brentuximab vedotin, and 1 received nivolumab plus ifosfamide, carboplatin, and etoposide. The median baseline CD4+ T-cell count was 155 cells/µL, which increased to 310 cells/µL at end-of-treatment (P=0.009). Three patients had grade 3 imAEs; none required treatment discontinuation. The ORR was 83% with median duration of response of 19.7 months. The median progression-free survival was 21.2 months and did not differ between patients with <200 versus ≥200 CD4+ cells/µL (P=0.95).ConclusionOur findings support the use of PD-1 blockade in HIV-cHL for the same indications as the general population with cHL.MicroabstractThere are limited data on PD-1 blockade in HIV-associated classical Hodgkin lymphoma (HIV-cHL). We retrospectively identified 23 patients with HIV-cHL safely treated with PD-1 blockade with a response rate of 83% that did not differ by CD4+ T-cell count. Our data support the use of PD-1 blockade in HIV-cHL for the same indications as the general population with cHL.

Background and Significance: Waldenström Macroglobulinemia (WM) is a rare indolent B-cell lymphoproliferative disorder which is defined by the presence of lymphoplasmacytic lymphoma (LPL) cells involving the bone marrow and production of a monoclonal IgM paraprotein. While upfront chemoimmunotherapy is highly effective, there is no standard-of-care therapy for relapsed patients who have progressed on BTK inhibitor therapy, and their prognosis is generally poor. Epcoritamab is a fully humanized CD20xCD3 T-cell-engaging bispecific antibody that redirects T-cells to eliminate B-cells and has shown promising activity in B-cell non-Hodgkin lymphomas in several pivotal trials leading to the regulatory approval in relapsed diffuse large B-cell and follicular lymphoma, following 2 or more prior lines or therapy. . Study Design and Methods: This single-arm, multicenter, phase 2 study will evaluate the efficacy and safety of epcoritamab in patients with relapsed or refractory (R/R) WM/LPL. It consists of a safety lead-in portion followed by a phase 2 portion to evaluate efficacy endpoints. The safety lead-in cohort will receive epcoritamab at a target dose of 24 mg. Patients in the Phase 2 efficacy cohort will be treated at a target dose of 48 mg. Of note, patients enrolled in the safety lead-in will subsequently be eligible for dose escalation to 48 mg and be able to complete an additional 12 months at that dose. Safety data will continue to be recorded; however, these patients will not be included in the efficacy analysis. Epcoritamab will be administered at a target dose of 24 or 48 mg subcutaneously over 28-day cycles for a maximum of 12 cycles. In cycles 1-3, epcoritamab will be given once per week (days 1, 8, 15, and 22); in cycles 4-9, every two weeks (days 1 and 15); and in cycles 10-12, once every four weeks (day 1). For cycle 1, a step-up dosing schedule will be utilized consisting of a priming dose of 0.16 mg (day 1), an intermediate dose of 0.8 mg (day 8), and a full dose of either 24 mg or 48 mg (day 15 onward). Patients with histologically confirmed R/R WM/LPL who have received ≥1 prior line of systemic therapy (including a BTK inhibitor) and have an Eastern Cooperative Oncology Group performance status of 0-2 meeting criteria for initiation of treatment per 2nd International Workshop for WM (IWWM2) criteria are eligible for enrollment. Exclusion criteria include known or suspected central nervous system (CNS) involvement (i.e., Bing-Neel Syndrome) or current uncontrolled CNS disease (including stroke, epilepsy, or vasculitis). The primary endpoint of this trial is the overall response rate (ORR) per modified IWWM6 criteria. A Simon's optimal two-stage design will be used for conducting the trial. The null hypothesis is that the true response rate is 0.5, and the alternative hypothesis is that the true response rate is 0.8. With a 2-sided alpha of 0.05 and a power of 80%, the sample size needed to reject the null hypothesis is 20 patients. Secondary endpoint include the rate of minor response (MR), partial response (PR), very good partial response (VGPR), and complete response (CR) at best response and after completing 6 months of study therapy, duration of response (DOR), the estimated 2-yr progression-free survival rate, time to next treatment (TTNT), and the estimated 2-yr overall survival rate. As exploratory objectives, we will evaluate serial single cell RNA to gauge changes in immune repertoire triggered by the bispecific expansion of immune cells and serial circulating tumor DNA for minimal residual disease detection and clonal evolution. If this study meets its primary endpoint, epcoritamab could be added to the armamentarium of safe and effective treatment options for WM patients.

Background Chimeric antigen receptor (CAR) T cells targeting CD30 are safe and have promising activity when preceded by lymphodepleting chemotherapy. We aimed to determine the safety of anti-CD30 CAR T cells as consolidation after autologous haematopoietic stem-cell transplantation (HSCT) in patients with CD30 + lymphoma at high risk of relapse. Methods This phase 1 dose-escalation study was performed at two sites in the USA. Patients aged 3 years and older, with classical Hodgkin lymphoma or non-Hodgkin lymphoma with CD30 + disease documented by immuno histo chemistry, and a Karnofsky performance score of more than 60% planned for autologous HSCT were eligible if they were considered high risk for relapse as defined by primary refractory disease or relapse within 12 months of initial therapy or extranodal involvement at the start of pre-transplantation salvage therapy. Patients received a single infusion of CAR T cells (2 x 10(7) CAR T cells per m(2) , 1 x 10(8) CAR T cells per m(2) , or 2 x 10(8) CAR T cells per m(2) ) as consolidation after trilineage haematopoietic engraftment (defined as absolute neutrophil count >= 500 cells per mu L for 3 days, platelet count >= 25 x 10(9) platelets per L without transfusion for 5 days, and haemoglobin >= 8 g/dL without transfusion for 5 days) following carmustine, etoposide, cytarabine, and melphalan (BEAM) and HSCT. The primary endpoint was the determination of the maximum tolerated dose, which was based on the rate of dose-limiting toxicity in patients who received CAR T-cell infusion. This study is registered with ClinicalTrials.gov (NCT02663297) and enrolment is complete. Findings Between lune 7, 2016, and Nov 30, 2020, 21 patients were enrolled and 18 patients (11 with Hodgkin lymphoma, six with T-cell lymphoma, one with grey zone lymphoma) were infused with anti-CD30 CAR T cells at a median of 22 days (range 16-44) after autologous HSCT. There were no dose-limiting toxicities observed, so the highest dose tested, 2 x 10(8) CAR T cells per m 2 , was determined to be the maximum tolerated dose. One patient had grade 1 cytokine release syndrome. The most common grade 3-4 adverse events were lymphopenia (two [11%] of 18) and leukopenia (two [11%] of 18). There were no treatment-related deaths. Two patients developed secondary malignancies approximately 2 years and 25 years following treatment (one stage 4 non-small cell lung cancer and one testicular cancer), but these were judged unrelated to treatment. At a median follow-up of 482 months (IQR 275-607) postinfusion, the median progression-free survival for all treated patients (n=18) was 323 months (95% CI 46 months to not estimable) and the median progression-free survival for treated patients with Hodgkin lymphoma (n=11) has not been reached. The median overall survival for all treated patients has not been reached. Interpretation Anti-CD30 CAR T-cell infusion as consolidation after BEAM and autologous HSCT is safe, with low rates of toxicity and encouraging preliminary activity in patients with Hodgkin lymphoma at high risk of relapse, highlighting the need for larger studies to confirm these findings.

Extranodal NK/T-cell Lymphoma (ENKTL) is a rare EBV associated lymphoma best characterized in Asian populations, with little data describing outcomes in North Americans. ENKTL has poor responses to traditional anthracycline-containing lymphoma regimens. Systemic agents such as asparaginase and gemcitabine, as well as radiation for localized disease, are considered important in improving outcomes. However, toxicity in older patients can be a limitation of therapy, especially with asparaginase based regimens. There is also no standard therapy for patients with ENKTL, especially those who may be older or have significant comorbidities. This analysis seeks to define treatment patterns and outcomes in for North American ENKTL patients with an emphasis on the impact of asparaginase use, including how asparaginase use and toxicity changes based on patient age. A retrospective, multicenter database included patients ENKTL patients older than 18 years diagnosed between 2010 and 2022. Clinical, pathologic, treatment and survival characteristics were collected. Survival was analyzed using the Kaplan-Meier method. Cox proportional hazards regression will be used to assess the relationship of characteristics (eg asparaginase exposure) and outcome. Predictive variables with p < 0.2 from the univariable analysis will be included in a multivariable analysis. All reported p values will be 2-sided, and the significance level will be at <0.05. Analysis of outcomes with age will occur both as categorical variables (<40yo, 40-60yo, 60+), and with age as a continues variable. Due to limited expected numbers, descriptive analysis of individuals will be provided for individuals 65+ and 70+. 134 patients from 8 academic institutions were included in the analysis. 42 (31.3%) patients were younger than 40 years old, 48 patients were between the ages of 40 - 60yo (35.8%), and 44 patients (32.8%) were 61 years and older. Eighty-four patients received asparaginase (ASP) and 50 did not (non-ASP). Grade 3+ transaminase elevations (AST or ALT >5x ULN) were common among pts receiving ASP seen in 23 of 84 patients (27%) versus those not receiving ASP (3 of 50, 6%). Lipase elevations were seen in 21 (25%) of asparaginase patients. Other notable toxicities in ASP vs non-ASP patients include hypertriglyceridemia (24% vs 0%), hypofibrinogenemia (24% vs 2%), neutropenic fever (20% vs 8%), hypersensitivity reactions (10% vs 2%), bleeding (8% vs 2%), VTE (5% vs 2%), and unplanned hospitalizations (31% vs 10%). In patients who received ASP, at least one AE was seen in 53% of patients <40yo, 68% between 40-60yo, and 66% of patients 61 years and older. Therapy related deaths were seen in 7 of the 84 patients who received ASP (8%) and in 4 of 50 patients non-ASP patients (8%). ASP was discontinued due to toxicity in 24 patients (28%). Overall (OR) and Complete (CR) response rates were 80% (62% CR) in the ASP group and 54% (46%) in the non-ASP groups. In patients <40yo, OR (CR) rates were 82%(64%) vs 57%(42%) in ASP vs non-ASP groups. In patients aged 40-60yo, OR(CR) rates were 76%(62%) vs 52%(47%), and in patients 61+, OR(CR) rates were 81%(59%) vs 53%(47%) in ASP vs non-ASP groups. Interestingly, the higher response rates did not translate to a statistically significant advantage in overall survival (p=0.44), with difference in PFS approaching statistical significance at 0.077. This analysis supports that ASP containing regimens have significant clinical activity in ENKTL, but are associated with significant rates of unique toxicities, resulting in discontinuation of ASP in a quarter of patients, but no increase in therapy associated death. The efficacy benefit as measured by response rates was maintained across age groups. We lacked statistical power to detect differences in survival, key subgroup analyses will be presented at the meeting in addition to other clinical, pathologic, and treatment variables. Additionally, we will discuss use of radiation, and more detailed characteristics of asparaginase dosing, and differences between chemotherapy backbones

Background: Chimeric antigen receptor T cells targeting CD30 (CD30.CAR-Ts) are efficacious in treating patients (pts) with relapsed/refractory (r/r) classical Hodgkin lymphoma (HL), but many pts relapse after treatment. We leveraged the CCL17 chemokine gradient of HL and conducted a phase 1 clinical trial to assess if CD30.CAR-Ts with enhanced tumor homing obtained by co-expressing the CCL17 chemokine receptor CCR4 (CCR4.CD30.CAR-Ts) promotes durable responses. Methods: Subjects on dose levels (DL) 1, 3 and 5 received CCR4.CD30.CAR-Ts only at a dose of 2x107, 5x107, and 1x108 CAR-Ts/m2 respectively, while subjects on DL 2, 4, and 6 received CCR4.CD30.CAR-Ts at the preceding DL plus a fixed dose of 1x108 CD30.CAR-Ts/m2 to compare the kinetics and biodistribution of the 2 products in the same patient. Dose escalation was guided by the 3+3 design. All pts received lymphodepletion (LD) with 3 days of bendamustine 70 mg/m2 and fludarabine 30 mg/m2 followed by CAR-T infusion 2-4 days later. Key eligibility criteria included age ≥ 18 years and diagnosis of r/r HL or cutaneous T cell lymphoma (CTCL) progressed after 2 or more prior lines of therapy, including brentuximab vedotin (BV). Results: Thirty-eight pts were enrolled with CAR-Ts manufactured successfully for 37 pts. Seven pts had product manufactured but were not treated due to ineligibility prior to treatment (n=3), death during the manufacturing period (n=3), or decision to pursue alternative therapy (n=1). Thirty pts were treated on protocol - 6 with CTCL and 24 with HL. This analysis focuses on pts with HL. Out of 24 pts with HL, 5 were treated on DL1, 2 on DL2, 3 on DL3, 3 on DL4, 2 on DL5, and 9 on DL6. The median age was 40 (range 27-75) and pts received a median of 6.5 prior lines of therapy, including BV and checkpoint inhibitor (CPI) in all pts, a prior autologous stem cell transplant in 22 pts and allogeneic stem cell transplant in 6 pts. The median time from collection to LD was 58.5 days (range 33-120). Eleven pts received bridging therapy, most frequently CPI (n=7). One pt had a partial response (PR) to radiation but the other 10 pts had either stable (n=4) or progressive disease (PD) (n=6) post bridging. No dose limiting toxicities were observed. Eight pts had cytokine release syndrome - 5 grade 1 and 3 grade 2 with a median time of onset of 8.5 days and median duration of 3 days. Four pts received tocilizumab. No pts experienced immune effector cell-associated neurotoxicity syndrome. The most common grade ≥ 3 toxicities were cytopenias, primarily attributed to LD, with 37.5% and 29% of pts with grade 3/4 neutropenia and thrombocytopenia, respectively at 4 weeks. Only 1 and 3 pts had persistent neutropenia and thrombocytopenia, respectively at 3 months post treatment. Sixteen pts (67%) had a complete response (CR), 6 (25%) had a PR and 2 (8%) had PD. Five pts are in ongoing CR, which remains durable at 3, 4, and 5 years post treatment in 3 pts. Six pts had biopsies post progression and all had persistent CD30 expression. At a median follow up of 29.6 months, the median progression free survival (PFS) is 6.4 months (95% CI: 3.6-11.5 months) and the median overall survival (OS) has not been reached. The median PFS for pts in CR is 9.3 months (95% CI: 5.8-16.4 months). The 1 year OS is 85% (95% CI: 60-95%). There were 4 deaths - 2 from infection >3 months post treatment and 2 from lymphoma. We observed the expansion of CCR4.CD30.CAR-Ts in the peripheral blood both in pts receiving CCR4.CD30.CAR-Ts alone and co-infused with both CAR-T products. Overall CCR4.CD30.CAR-Ts showed superior persistence to CD30.CAR-Ts (p=0.008, measured as AUC from week 4 after infusion) with CCR4.CD30.CAR signals still detectable 6 months post infusion in 12 of 14 (86%) evaluable pts vs CD30.CAR signals only detectable in 2 of 9 (22%) evaluable pts. Interestingly, these 2 pts were co-infused with both products at the same dose (1x108), suggesting a “helper effect” by CCR4.CD30.CAR-Ts. Plasma levels of CCL17, a biomarker of disease response for HL, were reduced by 86±13% by week 2 post-infusion in patients treated with CCR4.CD30.CAR-Ts as compared to 52±38% in our previous trial with CD30.CAR-Ts lacking CCR4 (p=0.007), suggesting that CCR4.CD30.CAR-Ts show faster antitumor activity. Conclusions: CCR4.CD30.CAR-Ts are safe with high response rates and durable remissions in a subset of pts with r/r HL. We are actively enrolling on a phase 2 clinical trial of CCR4.CD30.CAR-T cells at a dose of 2x108 CAR-Ts/m2 in pts with HL.

The treatment landscape of classical Hodgkin lymphoma has changed dramatically over the past decade. Relapsed and refractory mainstay therapeutics such as brentuximab vedotin (BV) and checkpoint inhibitors (CPIs) are being moved to earlier lines of therapy. However, the treatment of patients who progress after BV and CPI remains a challenge. Allogeneic stem cell transplantation still plays an important role in this patient population as the only current treatment approach with curative potential. Unfortunately, not all patients are transplant candidates, and many will still relapse afterward. Cytotoxic chemotherapy and radiation may be used for symptom palliation or as a bridge to transplant. Targeted therapies, including the antibody drug conjugate, camidanlumab tesirine, and transcriptional agents such mammalian target of rapamycin and histone deacetylase inhibitors have shown some potential in patients with refractory disease. In addition, combination therapies with CPIs and novel agents may help overcome resistance to therapy. Clinical trials with cellular therapies, including chimeric antigen receptor T cells targeting CD30 and allogeneic natural killer cells combined with AFM13, a CD30/CD16a-bispecific antibody, have shown promising results. The availability of more therapeutic options for this patient population is eagerly awaited.

Introduction: High-dose methotrexate (HD-MTX)-containing chemotherapy followed by either autologous stem cell transplant (ASCT) or whole-brain irradiation (WBI) is widely considered the standard for primary CNS lymphoma (PCNSL) treatment. However, many older frail patients with PCNSL are unable to undergo ASCT or WBI due to increased risk of treatment-related toxicity, such as infections and neurotoxicity. Without consolidation, survival outcomes are significantly worse, with a 3-year progression free survival (PFS) rate of ~ 30%. Therefore, novel therapeutic approaches are urgently needed for older PCNSL patients. Recently, nivolumab, an anti-PD1 antibody, showed promising clinical activities in relapsed/refractory PCNSL, and we hypothesized that addition of nivolumab in the frontline setting would be safe and improve survival outcomes of older PCNSL patients who are deemed poor candidates for ASCT or WBI. Methods: In this phase 1/1B single-arm multicenter study, patients ≥ 65, who were deemed poor candidates for ASCT and WBI, with previously untreated PCNSL received at least 3 cycles of HD-MTX-containing chemotherapy followed by nivolumab consolidation for 6 cycles (NCT 04022980). Patients with systemic lymphoma or known ocular involvement were excluded from the study. Stage 1 was designed to evaluate the safety of nivolumab consolidation after HD-MTX-containing induction chemotherapy. A 3+3 design was used as safety run-in, initiating 6 patients on nivolumab at the FDA-approved single-agent dose and monitoring for dose-limiting toxicities (DLTs) during Cycle 1. If less than 2 out of 6 subjects experienced a DLT, then the stage 2 part of study would initiate to evaluate the efficacy of nivolumab consolidation in terms of the 2-year PFS. The patient's neurological function was assessed at baseline and throughout the study follow-up using the Neurologic Assessment in Neuro-Oncology (NANO) scale. Results: A total of 14 patients enrolled in the study between April 2020 and December 2022 at 4 US sites. In 14 evaluable patients who underwent the study treatment, the median age was 72 years (range, 65-79), 71% patients were female, and 35% patients had ECOG score of 2 or 3. Variations of the following regimens were used for induction: 43% R-MPV (rituximab, methotrexate, procarbazine, and vincristine) (43%), 29% MRT (methotrexate, rituximab, and temozolomide), 21% MR (methotrexate and rituximab), and 7% MATRix (methotrexate, cytarabine, thiotepa, and rituximab). After induction, 58% achieved a complete response (CR), 33% achieved a partial response (PR), and 8% had a stable disease (SD). Patients received a median of 6 cycles of nivolumab consolidation. Patients who received at least 1 cycle of nivolumab consolidation achieved an overall response rate of 83% with a CR rate of 75%. With a median follow-up duration of 18 months, the 1-year overall survival (OS) and PFS rates were 91.7% and 66.1%, respectively. No DLTs were observed during Cycle 1 of nivolumab consolidation in Stage 1. The most common grade ≥ 3 Adverse Events (AEs) associated with nivolumab consolidation included neutropenia (14%) and fatigue (7%). One patient (7%) developed a grade 4 Stevens-Johnson syndrome associated with sepsis and acute kidney injury, requiring discontinuation of nivolumab after Cycle 1. Conclusion: The current study demonstrates encouraging safety and clinical outcomes of nivolumab consolidation in older PCNSL patients who are deemed poor candidates for ASCT or WBI. No DLT was observed during the safety run-in phase, and there was no unexpected toxicity associated with nivolumab although 1 patient discontinued the study treatment due to Stevens-Johnson syndrome, a rare but known AE associated with nivolumab, after Cycle 1. Overall, nivolumab consolidation was associated with favorable survival rates in a group of patients with poor-risk PCNSL. We are in the process of identifying various clinical and biological factors, including 9p24.1 copy number alteration, in association with the response to nivolumab consolidation. Furthermore, changes in the neurological function based on the NANO scale assessed before and after the nivolumab consolidation are being analyzed.

PURPOSE Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS This retrospective study included PWH treated with anti–PD-1- or anti–PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti–PD-1/anti–PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was –0.06 months (95% CI, –5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, –4.02 to 8.48; P = .48) for OS. CONCLUSION Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

Chimeric antigen receptor (CAR)-T cells targeting CD30 have demonstrated high response rates with durable remissions observed in a subset of patients with relapsed/refractory CD30+ hematologic malignancies, particularly classical Hodgkin lymphoma. This therapy has low rates of toxicity including cytokine release syndrome with no neurotoxicity observed in our phase 2 study. We collected patient-reported outcomes (PROs) on patients treated with CD30 directed CAR-T cells to evaluate the impact of this therapy on their symptom experience. We collected PROs including PROMIS (Patient-Reported Outcomes Measurement Information System) Global Health and Physical Function questionnaires and selected symptom questions from the NCI PRO-CTCAE in patients enrolled on our clinical trial of CD30-directed CAR-T cells at procurement, at time of CAR-T cell infusion, and at various time points post treatment. We compared PROMIS scores and overall symptom burden between pre-procurement, time of infusion, and at 4 weeks post infusion. At least one PRO measurement during the study period was found in 23 out of the 28 enrolled patients. Patient overall symptom burden, global health and mental health, and physical function were at or above baseline levels at 4 weeks post CAR-T cell infusion. In addition, PROMIS scores for patients who participated in the clinical trial were similar to the average healthy population. CD30 CAR-T cell therapy has a favorable toxicity profile with patient physical function and symptom burden recovering to at least their baseline pretreatment health by 1 month post infusion. Trial registration number: NCT02690545 .