Armand, Philippe

Abstract Use of brentuximab vedotin (BV) and PD-1 monoclonal antibodies (mAbs) before autologous stem cell transplantation (ASCT) could impact the benefit of post-ASCT BV maintenance in relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL). We identified 1091 patients with R/R cHL who underwent ASCT between 2010-2022. In total, 244 (22%) received a PD-1 mAb and 443 (41%) received BV before ASCT, while 305 (28%) received BV maintenance. We performed 1:1 propensity score matching to assess the efficacy of BV maintenance in different patient subgroups. Among 608 matched patients, the 3-year progression-free survival (PFS) and overall survival were 73% (95% confidence interval [CI], 70-78) and 95% (95%CI, 93-97), respectively. BV maintenance was associated with improved PFS for patients with no exposure to novel agents, especially those with 2+ modified AETHERA risk factors (0-1 factors: hazard ratio (HR), 0.51; 95%CI, 0.24-1.09; P =.083; 2+ factors: HR, 0.40; 95%CI, 0.25-0.65; P< .001). In contrast, BV maintenance was not associated with a significant PFS benefit for any patient subgroup who received novel agents before ASCT (BV-treated, 0-1: HR, 1.43; 95%CI, 0.53-3.81; P =.48; 2+: HR, 0.79; 95%CI, 0.34-1.82; P =.58; PD-1-treated, 0-1 [P>.99], 2+: HR, 0.25; 95%CI, 0.03-2.14; P =.21). In particular, we observed excellent outcomes for patients undergoing ASCT in a complete response after one line of PD-1-based salvage treatment with no significant benefit for BV maintenance observed (2-year PFS 100% vs 95%; P>.99). The benefit of BV maintenance appears to be attenuated for patients receiving novel agents with salvage therapy. Omission of BV maintenance should be considered for patients anticipated to have excellent outcomes.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin lymphoma provide expert, multidisciplinary recommendations for the diagnosis and treatment of Hodgkin lymphoma. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Hodgkin Lymphoma focuses on the management of newly diagnosed and relapsed/refractory classic Hodgkin lymphoma in adults aged 18 to 60 years.

Abstract Combination therapy incorporating programmed cell death protein 1 (PD-1) blockade results in unprecedented response rates in both frontline and relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). Previous retrospective studies have suggested benefit for PD-1 blockade before autologous stem cell transplant (ASCT) but included few patients receiving PD-1 blockade with cytotoxic chemotherapy. To explore the impact of anti–PD-1 based salvage on outcomes for patients with R/R cHL, we retrospectively reviewed 1280 patients with R/R cHL who underwent ASCT from 2010 to 2022 at 6 transplant centers, none of whom received PD-1 blockade as part of frontline therapy. Overall, 25% received a PD-1 inhibitor at any point before ASCT (10% in conjunction with chemotherapy), 28% received salvage brentuximab vedotin (BV) without PD-1 blockade, and the rest received salvage chemotherapy alone. Patients who received PD-1 inhibitors at any point before ASCT had a significantly higher 2-year progression-free survival than those who received BV without PD-1 inhibitors or patients receiving chemotherapy alone (88.2%, 70.2%, and 67.4%, respectively; P< .0001). When restricted to patients in complete response before ASCT, the benefit of PD-1 blockade remained significant. PD-1 blockade before ASCT is independently associated with superior post-ASCT outcomes and patients proceeding to ASCT should be treated with PD-1–based salvage.

Abstract Background Watchful waiting is a common option for pts with asymptomatic FL/MZL. Anti-tumor immunization may delay or even avoid subsequent need for more toxic therapies. EO is designed from non-self-protein sequences derived from gut bacteria, including 4 HLA-A2 CD8 T cell epitopes (synthetic mimic peptides), exhibiting molecular mimicry with specific epitopes on B cell markers (CD20, CD22, CD37, BAFF-receptor). EO also contains a CD4 helper epitope UCP2. EO expands pre-existing memory CD8 T cells recognizing non-self-epitopes from gut bacteria that cross-react with B cell antigens on tumor cells. Methods Cohort 2 (C2; planned accrual 25 pts) of EONHL1-20/SIDNEY includes HLA-A2+ pts with previously untreated FL/MZL not in need of treatment. Pts receive EO (300μg/peptide) SC with adjuvant Montanide, q2 weeks (w) x 4, then q4w, for 12 total doses. For antigen-specific immune responses, peripheral blood mononuclear cells were assayed by flow cytometry using EO-mimic or B cell peptide specific tetramers without in vitro stimulation. IFN-γ ELISPOT was used to evaluate response to UCP2 and anti-CD3. Primary endpoint is objective response rate (ORR) per Lugano 2014. A pre-defined futility boundary was applied (ORR uninteresting=5%/promising=20%). Finding at least 3 of 25 pts with ORR would meet criteria to continue development (chance of 13% and 90% for true ORR of 5% and 20%, respectively). Results As of July 2025, 22 pts had started EO. Median age 59 years (range 32-86); 9 female; 19 ECOG 0/3 ECOG 1; 19 FL/3 extranodal MZL (ENMZL); 3 Ann Arbor stage I-II/8 stage III/11 stage IV; FLIPI low risk 8/intermediate 8/high 6; FLIPI-2 low risk 12/intermediate 7/high 3; 19 GELF neg/3 pos. At a median follow-up for progression of 9.4 months, 9 pts completed EO, 4 stopped for progressive disease (PD), 2 due to PI/pt decision; 7 ongoing. Median treatment duration 38 w (range 4-39). Among 19 evaluable pts, best Lugano response was 3 complete (CR) and 6 partial responses (PR) (ORR 47% [95% CI 24%–71%]; CR-rate 16% [3%-40%]), 6 stable disease (SD), and 4 PD. ORR by PET-CT was 29% (n=14) w6, 39% (n=18) w19, 46% (n=13) w42; corresponding CR rates were 0%, 11%, 15%. Median time to response 17.1 w (range 5.3-41.1). Currently there are only 2 confirmed PD events in pts with prior PR/CR. Among 8 pts with an initial indeterminate response per LyRIC 2016 followed by a confirmatory scan, 4 pts did not have confirmed PD; a possible atypical response pattern rate of 50% on EO (occurring 5.3-41.9 w after start of EO). In 16 immune response evaluable pts, 88% and 81% had expansion of CD8 T cells specific for EO mimic and B cell target peptides, respectively. Expanded specific CD8 T cells had a memory phenotype dominated by effector memory (TEM) and central memory cells. At w5, 7 clinical responders and 7 non-responders were evaluable; more responders had a positive immune response against EO mimic (Chi-square p=0.025) and B cell target (p=0.047) peptides. Max expansion (response sum for 4 EO mimic or 4 B cell target peptides at a single timepoint w3-w8) of specific CD8 T cells (% of all peripheral CD8 T cells) was higher for responders than non-responders both for EO mimic (Mann Whitney p=0.018) and B cell target (p=0.017) peptides. Pts (4) with an initial indeterminate response (LyRIC 2016) had a higher max expansion of B cell target peptide specific CD8 T cells vs 4 pts with a typical progression pattern (Mann Whitney p=0.018) and vs all other 12 pts evaluable for immune response (p=0.029). There was no difference in CD4 T cell response to UCP2 in responders vs non-responders (induction or max immunity w3-w8). Anti-CD3 expansion of T cells indicating T cell intrinsic activation potential did not correlate with clinical response (baseline or max). The most common EO-related adverse events (AEs) were Gr (Grade) 1 (10 pts) and Gr 2 (6 pts) local administration site reactions. Other related AEs in >1 pt were Gr 1 headache (3 pts) and Gr 1-2 fatigue (3 pts). Asthenia lasting 2 days was the only related Gr 3 AE. There were 4 unrelated Gr 3 AEs (gastroenteritis, GI-hemorrhage, inguinal hernia, and syncope). There were no Gr 4-5 AE. ConclusionsEO has a favorable safety profile and is preliminary associated with an ORR of 47%, exceeding the pre-specified boundary for promising activity. The speed and level of expansion of both EO mimic and B cell target peptide specific CD8 memory T cells are associated with objective response. Results will be updated.

Abstract Background Single-agent R is a common 1st-line therapy for patients (pts) with FL, especially those with low-tumor burden advanced stage disease or comorbidities. EO is a therapeutic vaccine generated from non-self-protein sequences from gut bacteria, including 4 HLA-A2 CD8 T cell epitopes that mimic B cell-specific markers: CD20, CD22, CD37 and BAFF-receptor. EO also contains a CD4 helper epitope UCP2. EO expands pre-existing memory CD8 T cells recognizing non-self-protein sequences from gut bacteria which can cross-react with B cell antigens on tumor cells. The aim adding EO to R is to safely increase the depth and duration of responses. Methods Cohort 3 (C3) of trial EONHL1-20/SIDNEY includes pts with HLA-A2 and previously untreated low-tumor burden (GELF) FL grade 1-3A in need of treatment (per pt/treating physician). Pts receive EO (300μg/peptide) SC with adjuvant Montanide, q2 weeks (w) x 4, then q4w for a total of 12 doses, combined with R starting at w7 (375 mg/m2 IV q1w x4, then q8w x4). For immune responses blood mononuclear cells were assayed by flow cytometry and EO-mimic or B cell peptide specific tetramers without in vitro stimulation. The primary objective is to assess safety; secondary objectives include EO immunogenicity and preliminary efficacy. Results As of July 2025, the 6 planned pts had started EO. Median age was 66 years (range 46-73); 5 ECOG 0/1 ECOG 1; 1 Ann Arbor stage III/5 stage IV; FLIPI low risk 2/intermediate 2/high 2; FLIPI-2 low risk 2/intermediate 4. At median follow-up 10.6 months (mo) 4 pts completed and 2 are ongoing on EO. Median treatment duration was 43 w (range 2-43). Best response by Lugano in the 6 pts included 4 complete (CR) and 2 partial responses (PR). Median time to PR/CR was 17.1 w (range 6.0-18.0). Currently there is only 1 (not yet confirmed) progression at 20.5 mo. All 5 immune response evaluable pts had expansion of CD8 T cells specific for EO mimic and B cell target peptides during treatment; 4 of 5 had detectable expansions at w5 (1st testing time). Currently, the longest tested immune response is at w65 and positive for both EO mimic and B cell target peptides. Expanded specific CD8 T cells had a memory phenotype predominantly composed of effector memory (TEM) cells but also including central memory (TCM) and terminally differentiated effector memory CD8 T (TEMRA) cells. Across the 5 pts, the medians of max % (sum of specific CD8 T cells targeting either the 4 EO mimic peptides or the 4 B cell antigen epitopes at a specific timepoint) among all peripheral CD8 T cells were 0.71% (range 0.19-3.97) for EO mimic and 0.33% (0.20-1.30) for B cell target peptides. The most common EO-related adverse events (AEs) were local administration site reactions (erythema, pain, induration). These included Gr (Grade) 1 reactions in 3 pts, Gr 2 in 1 pt, and Gr 3 in 1 pt; latter being ulceration with EO-interruption at w10.1, and in context of a strong immune response against EO mimic [3.97% of all peripheral CD8 T cells at w5] and B cell target [1.30%] peptides, and CR from w16.7. Other EO related AEs were Gr 1 lymph node pain (1 pt), and related to both EO and R were Gr 2 urticaria (1 pt) and Gr 1 fatigue (1 pt). Only R related were Gr 2 infusion related reaction (3 pts), Gr 2 enterocolitis infection (1 pt), and in 1 pt each Gr 1 flushing, anemia, headache and diarrhea. There were no further Gr 3-4 AE and no death on treatment/follow-up. Complete B cell depletion was seen in 5 pts tested at w18 (R added w7); no recovery in the range of w30-65. Only 3 infections were reported, per above enterocolitis, and 2 cases of COVID-19 both resolved without sequalae. ConclusionsThe combination of EO with R has a predictable and manageable safety profile, with EO only adding local administration site reactions to the well-known R safety profile. In this feasibility cohort all evaluable pts developed a specific immune response against EO and B cell targets, and a Lugano objective response. The combination of EO and R is feasible and can be evaluated in further trials. Updated results will be presented at the meeting.

Abstract Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Although patients with FL have high response rates to therapy, most develop increasingly resistant disease. In addition, transformation into an aggressive lymphoma is associated with unfavorable outcomes. Many novel agents are under investigation, and early clinical data are encouraging. Aligning treatment with the underlying tumor biology and sequencing of therapies remain key clinical challenges. At the Lymphoma Research Foundation’s biannual 2024 Follicular Lymphoma Scientific Workshop, experts convened to discuss the role of chemotherapy in the context of new therapies, the impact of early progression on treatment sequencing, novel end points in clinical trials, disease biology and the tumor microenvironment, and new treatments on the horizon. This report focuses on updates in FL biology, first-line treatment, the role of progression of disease in 24 months, clinical trial design, and redefining cure in FL.

Introduction: Mantle cell lymphoma (MCL) is an uncommon B-cell non-Hodgkin lymphoma (NHL) Prognosis is highly variable due to underlying biological and molecular heterogeneity. The first-line (1L) treatment paradigm for MCL continues to evolve with increasing use of bruton tyrosine kinase inhibitors (BTKi) and decreasing use of autologous stem cell transplant (ASCT). TP53 alterations are associated with inferior outcomes in MCL. The aim of this retrospective study is to determine treatment strategies and clinical outcomes in MCL patients based on TP53 gene mutation status. Methods: Retrospective data were collected from 19 institutions in the United States from 1/1993 to 1/2024. We examined treatment patterns and outcomes among MCL patients >18 years of age with known TP53 mutation status by sequencing. Patients who did not receive treatment were excluded. The analysis was stratified based on presence of TP53 mutations. Systemic therapies were categorized as chemo-immunotherapy (CIT), non-chemotherapy (including monoclonal antibodies, lenalidomide, venetoclax, and novel agents on clinical trial), and regimens containing BTKi. The primary outcome was overall survival (OS) and secondary outcomes were progression free survival (PFS) and time to next treatment (TTNT). OS and PFS were estimated with the Kaplan-Meier method and log-rank tests were used to compare groups. Results: 645 patients were included in the study, with 468 men (72.6%) and median age was 64 years (range 30-89). 230/645 patients (35.7%) had a TP53 mutation, of which 182 (79%) were identified prior to 1L. While the male/female distribution was the same between the mutated and unmutated groups, median age at diagnosis and MIPI risk score was higher in the TP53 mutated group (age 65.9 vs 63.1 yrs, p= 0.015; MIPI 6.4 vs 6.1, p<0.001). TP53 unmutated patients had a median of 1 line of therapy vs. 2 for the mutated group (p<0.001, range 1-8). Blastoid histology and higher ki67 were also associated with the TP53 mutated group (p=0.045, 0.01 respectively) The median OS was 14.2 years for TP53 unmutated and 8.3 years for TP53 mutated patients (p<0.0001). PFS in 1L was 0.95 years in TP53 mutated compared to 2.02 years in TP53 unmutated group (p<0.0001). Selection of 1L therapeutic strategy was not associated with presence of TP53 mutation (Χ2 p= 0.21) although more patients in the TP53 unmutated group underwent ASCT (119/415 vs 38/230; Χ2 p=0.0006) TP53 mutation was associated with inferior survival compared to TP53 unmutated patients for CIT in 1L but the difference did not reach statistical significance when non-chemotherapy regimens and regimens containing BTKi were used. For CIT in 1L, 5 year OS was 78% [71-84%] for unmutated compared to 58% [48-67%] for the mutated group (p=0.0001 ). For non-chemotherapy regimens, 5 year OS for unmutated patients was 73% [52- 86%] compared to 52% [25-73%] for the mutated group (p=0.09). For regimens containing BTKi, 5 year OS for unmutated was 93% [81-97%] compared to 57% [28-78%] for mutated (p=0.07). Within the TP53 mutated group, there were no differences in any clinical outcomes between those receiving CIT, non-chemotherapy, or BTKi in 1L. While median OS appeared numerically longer in the BTKi group (14.4 yrs vs 8.8 yrs for CIT and 6.8 yrs for non-chemotherapy), the difference did not reach statistical significance (p=0.58). In contrast,TP53 unmutated patients who received CIT in 1L had better TTNT (p=0.0039) compared to those in non-chemotherapy and BTKi groups. There was no improvement in PFS (p=0.79) or OS (p=0.47). Conclusions To our knowledge this is the largest retrospective real world dataset of MCL treatment outcomes stratified by TP53 mutation. As in prior studies, TP53 mutation portends a worse prognosis in MCL compared to TP53 unmutated patients, but outcomes are better than historically reported. CIT in 1L was not associated with improved OS in either group. Irrespective of TP53 mutation status, incorporation of BTKi in first line was not associated with improved clinical outcomes. The gap in OS between TP53 mutated and unmutated MCL may be narrowing as treatment paradigms shift away from intensive induction chemotherapy and ASCT, and due to an increasing number of effective therapies for relapsed patients. Clinical trials of novel agents are needed to further improve the OS of TP53 mutated MCL patients.

Background Follicular lymphoma (FL) is a generally indolent disease where a watch and wait strategy is standard in asymptomatic patients (pts) with a low tumor-burden. Harnessing antitumor immunity through an anti-tumor immunization strategy at this stage may delay or avoid the subsequent need for more toxic and complex therapies. EO2463 is a therapeutic vaccine designed from non-self protein sequences, derived from gut bacteria, including 4 HLA-A2 synthetically produced 9-mer CD8 cytotoxic T cell epitopes, exhibiting molecular mimicry with specific epitopes on the B cell markers CD20, CD22, CD37, and CD268 (BAFF-receptor). Additionally, EO2463 contains a CD4 helper epitope UCP2 derived from hTERT. The compound expands pre-existing memory CD8 T cells recognizing the non-self protein sequences from gut bacteria which can then cross-react with the selected B cell antigens on tumor cells. EO2463 is being used to drive anti-tumor immunity against B cell malignancies, and has demonstrated long-lasting, specific CD8-memory T cell responses and clinical activity in relapsed/refractory FL and marginal zone lymphoma (MZL) [J Clinical Oncol 2024, 42 (S16), 7058]. Furthermore, CD8 T cells expanded from samples of patients treated with EO2463 can kill HLA-A2 expressing lymphoblastoid cell lines presenting the B cell targets [Hematological Oncol 2023, 41 (S2), 581-582]. Methods The current report describes Cohort 2 of trial EONHL1-20/SIDNEY (NCT04669171) and includes pts with newly diagnosed, previously untreated FL, grade 1-3A, HLA-A2, and not in need of treatment. Pts receive EO2463 (300μg/peptide) SC with adjuvant Montanide ISA 51 VG, q2 weeks (w) x 4, then q4w, for a total of 12 doses (39w; PET-CTs at w6, w19, and w42). Planned accrual for this cohort is 25 pts. Immune responses were assayed on thawed pt peripheral blood mononuclear cells by flow cytometry and EO2463 peptide specific tetramers or by IFN-γ ELISPOT (assaying responses against 9-mer peptides from CD20, CD22, CD37, and CD268; and from peptides of EO2463) without any proceeding in vitro stimulation (ex vivo). Results As of June 2024, 15 pts had started study treatment. Median age was 62 (range 55-66) year, 7 male and 6 female, 2 pts Ann Arbor stage I/II, 5 stage III, and 8 stage IV. Ten of 15 pts were still on treatment; median treatment duration was 18.4 weeks (range 5-39 w) for all pts. Among 13 evaluable pts, best responses by PET-CT using Lugano criteria were 1 pt CR, 5 pts PR (46% objective responses (OR)), 3 pts SD, and 4 pts PD. Of those with PD per Lugano, 2 had isolated increases in FDG-uptake without increase in lesion size/number at w6 and both remain on treatment (per protocol based on LYRIC criteria). OR was first noted w6 in 3 pts and w19 in 3 pts; duration of response is not evaluable at this time due to short follow-up. The pt with CR had isolated increases in FDG-uptake at w6, PR at w19, and CR at w35. Anti-EO2463 immune responses were observed in 4 of 5 tested pts at the 1st testing timepoint (w5) and onwards (currently longest tested up until w31). In an exploratory analysis, the percentage of EO2463 peptide specific CD8 T cells measured by tetramers seemed linked to clinical response (OR 3 pts vs non-OR 2 pts; 2-sided T-test, p=0.02; range of percentages in pts with OR 0.85%-1.39% of all CD8 T cells in peripheral blood, range in pts with non-OR 0.17%-0.27%). Functionality and cross-reactivity of responses were shown by IFN-γ ELISPOT using 9-mer peptides corresponding to the B cell targets in 4 tested pts. Expanded antigen-specific CD8 T cells displayed a memory phenotype; effector/memory (TEM), and terminally differentiated effector memory CD8 T cells (TEMRA). The most common related AEs were grade 1 (7 pts) and grade 2 (5 pts) local administration site reactions (mainly erythema, pruritus, and induration). Other related AEs in > 1 pt were grade 1 headache (2 pts) and grade 1-3 fatigue/asthenia (3 pts). Asthenia lasting 2 days was the only related grade 3 adverse event (AE). Conclusions EO2463 monotherapy is associated with a very manageable safety profile and appears to demonstrate meaningful single-agent efficacy in FL. Consistent with the preclinical hypothesis, expansion of specific CD8 memory T cells may be associated with response. Results will be expanded at the meeting. Study EONHL1-20/SIDNEY also includes cohorts, not covered in this abstract, exploring EO2463 plus rituximab for 1st line FL/MZL, and EO2463 plus lenalidomide/rituximab in relapsed FL/MZL.

Background Follicular and marginal zone B cell lymphoma (FL; MZL) demonstrate an indolent course with heterogeneous outcomes and a potential for spontaneous remissions indicating immune system intervention. T cell-based therapeutic approaches are therefore an attractive proposition in FL and MZL. EO2463 peptide immunotherapy expands pre-existing memory CD8 T cells recognizing non-self-protein sequences from gut bacteria which cross-react with B cell antigens. The compound includes 4 HLA-A2 synthetically produced epitopes which exhibit molecular mimicry with the B cell markers CD20, CD22, CD37, and CD268 (BAFF-receptor), as well as a the CD4 helper-epitope UCP2 derived from hTERT. EO2463 is being used to drive anti-tumor immunity against B cell malignancies, and has demonstrated long-lasting, specific CD8-memory T cell responses and clinical activity in relapsed/refractory FL and MZL [J Clinical Oncol 2024, 42 (S16), 7058]. Furthermore, CD8 T cells expanded from samples of patients (pts) treated with EO2463 can kill HLA-A2 expressing lymphoblastoid cell lines presenting the B cell targets [Hematological Oncol 2023, 41 (S2), 581-582]. Methods The current report describes testing of a possible biomarker in the phase 1 portion of the ongoing EONHL1-20/SIDNEY trial (NCT04669171).This part of the trial (“Cohort 1”) included pts (n=9) with relapsed (at least 1, no limit, prior treatments) FL and MZL, stage 1-3A, confirmed to be positive for HLA-A2. Pts received EO2463 (150 [n=3] or 300μg/peptide [n=6]) SC with adjuvant Montanide ISA 51 VG q2 weeks (w) x 4, then q4w, for a max of 12 months; at w7 lenalidomide (20 mg/day for 21/28 days up to 12 cycles) was added (EL), and if no complete remission (CR) at w19, rituximab (375 mg/m IV, q1w x 4, then q4w x 4) was also added (ER2). Immune responses and clinical outcomes of Cohort 1 were previously reported [J Clinical Oncol 2024, 42 (S16), 7058]. To assess a possible biomarker, tetramers were used to specifically detect CD8 T cells recognizing the 4 epitopes in the EO2463 compound (derived from gut bacterial proteins exhibiting molecular mimicry with the B cell markers CD20, CD22, CD37, and CD268). The tetramers were all marked with phycoerythrin. Thawed samples of peripheral blood mononuclear cells taken at start of w5 (after 2 administrations of EO2463 monotherapy, each followed by 2w observation) were stained ex vivo (without any in vitro stimulation) with the tetramers and assayed by flow cytometry. Results are presented as percentage of EO2463 specific CD8 T cells among all CD8 T cells in the peripheral blood of the pt. Results Among the 9 treated pts, PET-CT at w6 (after 3 administrations of EO2463 monotherapy) suggested possible clinical activity in 4/9 pts (1 PR, 1 pt size reduction 15%, 1 pt 20% reduced tracer uptake, 1 pt 5/6 target lesions reduced metabolic activity). By PET-CT at w42 (after 12 administrations of EO2463 monotherapy, 11 cycles of lenalidomide, and rituximab treatment) the Lugano response assessment was complete response in 6/9 pts. A positive biomarker response was assessed in 5/9 pts (percentage of specific CD8 T cells ranged from 0.2-2.1%). EO2463 monotherapy PET-CT activity at w6 (n=4/9 pts): 4 of 4 pts with clinical activity were biomarker positive and 1/5 of the other pts was also positive; this pt had an isolated increase in FDG-uptake at w6, followed by a CR at w19. Four further other pts were biomarker negative. In this limited sample, the biomarker had sensitivity 100% and specificity 80%. EO2463 in combination with lenalidomide/rituximab PET-CT CR at w42 (n=6/9): 5 of 6 pts with CR were biomarker positive and 1 pt with CR was negative; the pt with a negative test had no objective tumor response until after rituximab. In this limited sample, the biomarker showed sensitivity 83% and specificity 100%. Conclusions The current preliminary assessment indicates that direct ex vivo tetramer staining for specific CD8 T cells after short term (5 w) treatment with EO2463 monotherapy could be a possible biomarker for clinical response, both for EO2463 monotherapy response, and for response to EO2463 in combination with lenalidomide/rituximab. We plan to validate these findings in the ongoing study cohorts of the trial; expansion phase 2 cohorts, exploring EO2463 monotherapy in the “watch & wait” setting, EO2463 plus rituximab for 1st line FL/MZL, and EO2463/lenalidomide +/- rituximab in relapsed FL/MZL.