AbstractBackgroundWe report extended follow-up of TROG99.03, a randomised phase III trial in early-stage follicular lymphoma (ESFL) including new information on the role of adjuvant rituximab and translational studies.MethodsPatients with ESFL were randomised to involved-field radiotherapy (IFRT) or IFRT plus 6-cycles cyclophosphamide/vincristine/prednisolone (IFRT+CVP). From 2006 rituximab was added to IFRT+CVP (IFRT+R-CVP). Clinical and multi-omic parameters were evaluated. Findings were validated in two independent ESFL cohorts (99 and 60 patients respectively).FindingsBetween 2000-2012, 150 (75 per arm) patients were recruited. 48% were positron emission tomography (PET)-staged. Per protocol, at median follow-up 11.3-years, progression-free survival (PFS) remained superior for IFRT+(R)CVP vs. IFRT (hazard ratio [HR]=0.60, 95%CI=0.37-0.98, p=0.043; 10-year PFS 62% vs. 43%) respectively. Although no significant difference in overall survival was observed (HR=0.44, 95%CI=0.16-1.18, p=0.11, 10-year OS 95% vs 84%), patients receiving IFRT+(R)CVP experienced fewer composite (histological transformation and death) events (p=0.045). PFS of IFRT+R-CVP-treated patients compared with all other treatments lacking rituximab (IFRT alone plus IFRT+CVP) was superior (HR=0.36, 95%CI=0.13-0.82, p=0.013). Amongst PET-staged patients, PFS differences between IFRT+R-CVP vs. IFRT were maintained (HR=0.38, 95%CI=0.16-0.89, p=0.027) indicating benefit distinct from stage migration. FL-related mutations andBCL2-translocations were not associated with PFS. However, by multivariate analysis elevated CD8A gene expression in diagnostic biopsy tissue was independently associated with improved PFS (HR=0.45, 95%CI=0.26-0.79, p=0.037), a finding confirmed in both ESFL validation cohorts. CD8A gene expression was raised (p=0.02) and CD8+ T-cell density higher within follicles in ESFL vs. advanced-stage FL (p=0.047). Human leucocyte antigen class I specific neoantigens were detected in 43% of patients, suggesting neoantigen-specific CD8+ T-cells have a role in confining the spread of the disease.InterpretationAdjuvant R-CVP and elevated intratumoural CD8 expression were independently associated with sustained disease control after radiotherapy in ESFL.FundingCancer Council Victora; National Health and Medical Research Council; Leukaemia Foundation; Mater Foundation.

Background Peripheral T-cell lymphomas (PTCLs) are a diverse group of aggressive non-Hodgkin lymphomas characterized by a high relapse rate and poor prognosis in the relapsed/refractory (r/r) setting. Despite advances in treatment, there remains a critical need for new therapeutic strategies. This study investigates the combination of Pembrolizumab, an immune checkpoint inhibitor, and Romidepsin, a histone deacetylase inhibitor, based on the hypothesis that PTCLs harbor mutations in epigenetic modifier genes that may impair immunogenicity and promote immune escape. The combination aims to synergistically prime the immune system, potentially enhancing anti-tumor responses. Here, we present updated results from our phase I/II study (NCT03278782), including survival analysis and integrated spatial and genomic data, to correlate the efficacy of this novel therapeutic approach in r/r PTCL patients. Methods We enrolled 38 patients (pts) between February 2018 and April 2022. Treatment consisted of Pembrolizumab (200 mg, day 1) and Romidepsin (14 mg/m², days 1 and 8) in 21-day cycles, with a maximum of 35 cycles. The primary endpoint was overall response (OR: CR+PR) using Lugano Revised Response Criteria, with secondary endpoints of progression-free survival (PFS), overall survival (OS), and exploratory studies. Correlative studies were performed in 26 pt samples to delineate components of the tumor microenvironment (TME) contributing to primary or acquired resistance to immune checkpoint blockade. These included CODEX analysis of 122 phenotypes using 33 different markers, whole exome sequencing (WES), RNA-seq, targeted next-generation sequencing (NGS), and whole slide image (WSI) analysis. Survival analysis was conducted using R and Python with a p-value threshold of ≤0.05. Results Patient characteristics (n=38) included: median age 67, 57.9% male, 86.8% >60 years, 68.4% with elevated LDH, 63.2% at Stage III/IV. Common ≥grade 3 adverse events were infections (n=11) and thrombocytopenia (n=10). Three patients discontinued due to immune-related adverse events (iRAEs), while two continued after steroid treatment. Response rates varied by PTCL subtype, with best responses for the TfH/AITL subtype showing CR 57.1%, PR 28.6%, ORR 85.7%. At a median follow-up of 40 months (Mo), median OS was 21.32 months (TfH vs. PTCL: 65 vs. 16.6 Mo, p=0.024). OS rates were: 1-year 67.9%, 2-year 48.7%, 3-year 36.7%. Median PFS was 3.6 Mo (TfH vs. PTCL-NOS: NR vs. 1.23 Mo, p=0.013), with PFS rates: 1-year 42.1%, 2-year 36.8%, 3-year 34.0%. CODEX analysis revealed higher levels of cytotoxic T cells (CD3+CD8+), macrophages (CD68+), and proliferating B cell subset (CD20+Ki67+) in responders. Non-responders showed higher levels of CD4+PD1+ T cells, suggesting T cell exhaustion. Spatial analysis showed CTLs were generally closest to Tregs across most lymphoma subtypes, with subtype-specific variations in cellular distances and clustering coefficients. RNA-seq analysis of 10 samples revealed distinct clustering of responders and non-responders in PCA and heatmap analyses of the top 500, 800, and 1000 variable genes. NGS showed heterogeneity in genetic alterations with top genes including TET2, DNMT3A, RHOA, IDH2, PLCG1, CD28, FYN, and STAT3. Finally, WSI analysis (n=27) using machine learning and deep learning techniques identified patch clusters that correlated with outcomes. Conclusions The combination of Romidepsin and Pembrolizumab leads to high response rates and prolonged remissions in r/r TCL, particularly in the TFH subtype. The exploratory analysis revealed a clear separation of responders and non-responders based on WES, CODEX and spatial analysis. WES and RNA-seq show significant genetic and transcriptomic heterogeneity among the samples, with some patterns potentially associated with treatment response. CODEX displayed a more diverse and active immune profile in responders, including higher levels of cytotoxic T cells, B cells, and macrophages, with subtype-specific variations in the TME. Through single-cell analysis, we were able to simultaneously detect various biomarkers in neoplastic cells and the immune microenvironment while considering spatial relationships. Further integration of biomarker for treatment response and resistance mechanisms will be presented at the annual meeting.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While induction chemotherapy leads to remission in most patients, a significant number will experience relapse. Therefore, there is a need for novel therapies that can improve remission rates in patients with relapsed and refractory AML. CD70 is the natural ligand for CD27 (a member of the TNF superfamily) and appears to be a promising therapeutic target. Consequently, there is considerable interest in developing chimeric antigen receptor (CAR) T-cell therapy products that can specifically target CD70 in various neoplasms, including AML. In this study, we employed routine diagnostic techniques, such as immunohistochemistry and flow cytometry, to investigate the expression of CD70 in bone marrow samples from treatment-naïve and relapsed AML patients after hypomethylating agents (HMA). Also, we evaluated the impact of HMA on CD70 expression and examined CD70 expression in various leukemic cell subsets and normal hematopoietic progenitors.

Introduction. Chemoimmunotherapy (CIT) with bendamustine and rituximab (BR) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) represent the standard frontline treatment for patients with advanced and high tumor burden follicular lymphoma (FL). The combination of lenalidomide and rituximab (R2) has shown similar efficacy to frontline CIT. While clinical prognostic scores such as FLIPI, FLIPI-2 and PRIMA-PI have been developed in CIT-treated patients, predictive biological tools for frontline treatment selection are currently lacking for FL. Lymphoma molecular subtyping, identified through transcriptomic characterization of the lymphoma microenvironment (LME), and precise reconstruction of its composition, through deconvolution, have been shown to predict outcomes in patients with large B-cell lymphoma (Kotlov et al., Cancer Discov, 2021). It remains unclear, however, whether molecular immune signatures could also be utilized for treatment selection in FL patients. Methods. Pre-treatment tissue biopsies were collected from patients with advanced and high tumor burden FL treated with frontline BR, RCHOP, or R2 and with available follow-up clinical data. Baseline clinical and laboratory characteristics were retrospectively used to calculate FLIPI, FLIPI-,2 and PRIMA-PI scores. Response and survival were assessed according to 2014 Lugano criteria. Bulk RNA sequencing was generated for LME subtyping, cell deconvolution using the Kassandra algorithm (Zaitsev et al., Cancer Cell, 2022), B-cell associated gene signatures (BAGS) analysis, and B-cell receptor (BCR) repertoire analysis. Mann-Whitney test was used for comparing continuous variables between patient groups. The log rank test was used to assess the difference in progression-free survival between patient groups. Results. The analysis included 35 patients: 12 treated with frontline BR, 12 with frontline RCHOP, and 11 with frontline R2. Twenty-three (66%) had high FLIPI scores, 14 (40%) had high FLIPI-2 scores, and 7 (20%) had high PRIMA-PI scores. Patients with high FLIPI score (3‒5) displayed a significant decrease in BCR diversity as compared to those with low-intermediate FLIPI score (0‒2), shown by smaller Shannon and higher Simpson indexes. In addition, patients with higher FLIPI scores (evaluated as a continuous variable) tended to have higher T-regulatory (T-reg) and T-reg traffic signature scores. No significant associations were observed between LME subtypes, BAGS, cell deconvolution, or BCR repertoire and FLIPI-2 or PRIMA-PI scores. Median follow-up for the whole cohort was 122 months (95% confidence interval [CI], 107-146 months) and median progression-free survival (PFS) was 143 months (95% CI, 98.6-NA months). No significant difference in median PFS was observed when comparing CIT-treated patients (BR or RCHOP) to R2-treated patients (p=0.27). However, when analyzing PFS within the 4 BAGS subgroups [light-zone like (n=7), dark zone-like (n=10), normal-like (n=13), and plasma cell-like(n=5)], patients with normal-like BAGS experienced a significantly longer median PFS when treated with BR (not reached [NR]) compared to RCHOP (143 months) or R2 (31 months)(p=0.05), and PFS with CIT compared to R2 (NR vs 31 months, p=0.03). In addition, analysis of T-cell signature, including CD3D, CD3G, TRBC1, TRAT1, TRAC, CD3E, CD28, TRBC2, ITK, and TBX21, categorized as high or low based on the cohort median, revealed patients receiving frontline R2 with high T-cell signature scores to experience significantly longer median PFS compared to those with low T-cell signature scores (NR vs 21 months, p=0.04). No association between treatment modality and PFS based on TME subtypes was observed. Discussion. While FLIPI scores are associated with the molecular features of FL, including BCR diversity and T-reg signatures, clinical prognostic scores have a limited impact in biological signatures. Our findings suggest that longer PFS could be achieved by using CIT to treat patients with normal-like BAGS and R2 to treat those with high T-cell signature scores. Pending validation with large datasets and clinical trials, these findings suggest that pre-treatment molecular immune signatures may facilitate frontline treatment selection in FL.

Background: The prognosis for patients with AML and MDS who relapse after allogeneic stem cell transplant (allo-SCT) is dismal. AML is susceptible to immunotherapy, as evidenced by the success of allo-SCT. Enhancing graft-versus-leukemia effect of allo-SCT is a major area of focus. We investigated combination immune checkpoint inhibition (ICI) using ipilimumab (Ipi) and nivolumab (Nivo) in a phase I dose escalation trial enrolling AML/MDS patients who relapsed after allo-SCT. Patients and Methods: For AML, evidence of relapse included bone marrow blast count ≥5% and/or presence of extramedullary disease and/or presence of marrow measurable residual disease (MRD) by multicolor flow cytometry. For MDS, evidence of relapse included appearance of dysplastic changes in the marrow, with or without increase in marrow blast count. Patients, ≥18 years-old, with a matched or haploidentical related donor, or 8/8 HLA matched unrelated donor (MUD) received Nivo (1mg/Kg) monotherapy administered on Day 1 and 15 of a 4 week cycle; ipilimumab (1mg/Kg) monotherapy administered on day 1 of a 3 week cycle; or combination Nivo (1 or 3 mg/Kg) + Ipi (1 or 3 mg/Kg), with Nivo and Ipi administered on day 1, followed by Nivo on days 15 and 29 of a 6 week cycle. Drug(s) were started > 42 days after stem cell infusion. Graft versus host disease (GVHD) prophylaxis was post-transplant cyclophosphamide 50 mg/kg on day +3 and +4, and tacrolimus ± MMF. Patients with history of >grade 2 GVHD were excluded. The primary outcome was to determine maximum tolerated dose (MTD) and dose limiting toxicity of monotherapy and combination Ipi + Nivo. ClinicalTrials.gov: NCT03600155. Results: 29 patients, 10 females and 19 males, with a median age of 59 (27-76) years were enrolled between April 2019 and May 2023. Of the 29 patients, 20 (69%) had AML, 7 (24%) had MDS, and 2 patients (7%) had CMML. Twenty-six (90%) patients had marrow disease only, 1 patient (3%) had extramedullary disease, and 2 patients (7%) had involvement of both. Twenty-two (76%) patients with AML and MDS had morphologic relapse, and 7 (24%) AML patients had MRD by flow cytometry. Five patients (33%) had a history of grade I GVHD and 10 (67%) patients had a history of grade II GVHD; in all cases, symptomatic GVHD resolution was achieved prior to study initiation. The median time from administration of SCT to study drug infusion was 179 days (range, 54-987). Seventeen (59%) patients were on GVHD prophylaxis during the study. Twenty-seven patients (93%) had received post SCT cyclophosphamide. Four patients (14%) developed GVHD on study. Of the 4 patients who developed GVHD, 2 (50%), 1 (25%) and 1(25%) patients developed grade II (skin and upper GI [UGI]), III (UGI and lower GI [LGI]) and IV (LGI) GVHD, respectively. Twenty-nine (100%), 28 (97%), 29 (100%), 16 (55%), and 7 (24%) patients experienced grades I, II, III, IV and V toxicities, respectively. Typical adverse events associated with ICI included: pneumonitis (n=3; 10%), 2 (7%) grade II and 1 (3%) grade III; colitis (n=3; 10%), 1 (3%) grade II, 1 (3%) grade III and 1 (3%) grade IV; hepatitis (n=6; 21%), 2 (7%) grade 1, 2 (7%) grade II, 1 (3%) grade III and 1 (3%) grade IV; endocrinopathy (n=3; 10%), 1 (3%) grade I, 1 (3%) grade II, and 1 (3%) grade III; dermatitis (n=4; 14%), 1(3%) grade 1, and 3 (10%) grade III. Dose limiting toxicities were noted at combination nivo 1 mg/Kg + Ipi 3 mg/Kg, mandating Ipi dose reduction to 1mg/Kg. During the study period, median follow-up was 65 days (range, 9-277 days); 13 patients experienced disease progression, GVHD, or death. Median PFS, estimated using Kaplan-Meier method, was 109 days (95%CI: 48 - NA days). Nine (31%) patients achieved stable disease or remission: 4 patients on Nivo 1 mg/Kg arm, 2 patients on Ipi 1 mg/Kg arm, 2 patients on Nivo + Ipi 1 mg/Kg arm, and 1 patient on the Nivo 3 mg/Kg + Ipi 1 mg/Kg arm. Patients with MDS had a longer PFS (HR = 0.15; CI, 0.02-1.18; p=0.03) vs. patients with AML. Of patients with extramedullary disease, 1 patient had CR of skin lesions and the second patient had a mixed response; both patients received Nivo 1mg/Kg + Ipi 1mg/Kg arm. Comprehensive immune profiling using CyTOF enabled the identification of distinct stem cell subsets and myeloid and lymphoid populations in bone marrow aspirates and circulating blood. Conclusion: This study met its primary objective of determining the MTD of the combination regimen with encouraging safety and efficacy outcomes. Our results warrant further study of this regimen.

Adult T-cell leukemia-lymphoma (ATLL) is an aggressive malignancy driven by human T-cell leukemia virus type 1 (HTLV-1). Although patients from the Western hemisphere (Afro-Caribbean and South American) face worse prognoses, our understanding of ATLL molecular drivers derives mostly from Japanese studies. We performed multi-omic analyses to elucidate the genomic landscape of ATLL in Western cohorts. Recurrent deletions and/or damaging mutations involving FOXO3, ANKRD11, DGKZ, and PTPN6 implicate these genes as potential tumor suppressors. RNA-sequencing, published functional data and in vitro assays support the roles of ANKRD11 and FOXO3 as regulators of T-cell proliferation and apoptosis in ATLL, respectively. Survival data suggest that ANKRD11 mutation may confer a worse prognosis. Japanese and Western cohorts, in addition to acute and lymphomatous subtypes, demonstrated distinct molecular patterns. GATA3 deletion was associated with chronic cases with unfavorable outcomes. IRF4 and CARD11 mutations frequently emerged in relapses after interferon therapy. Our findings reveal novel putative ATLL driver genes and clinically relevant differences between Japanese and Western ATLL patients.

S260the context of currently utilized extended post-ASCT maintenance therapy.Furthermore, the impact of more intensive regimens, beyond standard single-agent lenalidomide maintenance, on normal plasma cells has not been extensively studied.Methods: Using published results of the unplanned interim report (Dytfeld, Lancet Oncology 2023), we performed a longitudinal analysis of polyclonal immunoglobulin concentrations and unique B-cell sequences in patients enrolled in the phase 3 ATLAS trial that randomized 180 subjects to either carfilzomib, lenalidomide, dexamethasone (KRd) or lenalidomide (R) maintenance.In the KRd arm, patients with standard risk and minimal residual disease (MRD) negativity after 6 cycles de-escalated to R alone after cycle 8.Results: One year from the initiation of maintenance, complete recovery of uninvolved immunoglobulin was observed in 8/140 (5.7%) evaluable patients and partial recovery (at least one uninvolved immunoglobulin) in 86/140 (61.4%).At least partial recovery was observed in more patients on the R arm (58/66, 87.9%, p< 0.001) and in those who de-escalated from KRd to R (27/38, 71.1%, p< 0.001) compared to the KRd arm (9/36, 25.0%).The concentration of polyclonal immunoglobulin and the number of total unique B-cell sequences were significantly lower in patients who received continuous treatment with KRd throughout the analyzed period (cycles 6, 12, 18, 24, 30, 36).In patients who switched from KRd to R after cycle 8, the concentrations of uninvolved immunoglobulin and B-cell repertoire diversity increased over time after de-escalation, approaching values observed in the control R arm.At MRD assessment after C6, the concentration of uninvolved immunoglobulin was significantly lower among MRD-negative patients (p=0.03).There were no differences in PFS [HR = 1.07 (0.54-2.10), p=0.85] or OS p=0.76] between the patients with at least partial immunoglobulin recovery and the remaining population.The differences in PFS were not significant also when adjusted for the study arm.Conclusions: The findings from our study show that polyclonal immunoglobulin recovery one year after ASCT does not have prognostic significance for PFS after extended treatment with KRd versus R, indicating limited prognostic significance of polyclonal immunoglobulins recovery in the context of contemporary landscape of maintenance therapies.

Supplementary Data from Identification and Targeting of the Developmental Blockade in Extranodal Natural Killer/T-cell Lymphoma

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma subtype characterized by proliferation of lymphocyte-predominant (LP) cells associated with a distinct tumor microenvironment. Six major histopathological growth patterns (A to F) have been described by Fan and colls., based on the cellular composition of the tumor microenvironment and its relationship with the LP cells. Group I (patterns A to C) is comprised of nodules rich in small B-cells and follicular dendritic cells and have been associated with low-risk of disease recurrence/progression, while group II (patterns D to F) is rich in small T-cells, lack follicular dendritic cells and have a higher risk of disease recurrence/progression. Although multiple studies have characterized the tumor microenvironment and its relationship with tumor biology in classic Hodgkin lymphoma and other lymphoma types, these studies are limited for NLPHL. Regulatory T-cells (Tregs), a highly immunosuppressive subset of CD4+ T cells, represent a key cellular player in the tumor microenvironment by limiting antitumor immune responses. Emerging studies suggest substantial heterogeneity in the immunophenotype and suppressive capacities of Tregs. For example, classic Tregs are positive for CD4, CD25 and FOXP3; however, a highly immunosuppressive subset of Tregs, named Tr1-like cells has been recently identified and characterized by a distinctive immunophenotype (CD4+, EOMES+, GZMK+ but Foxp3- CD25-) and distinct cytokine expression. Tr1-like are highly relevant in cancer because they seem to be clonally expanded in solid tumors and its presence and number correlates with disease progression (Bonnal et al. Nat Immunol, 2021). Here, we aimed to investigate the Tregs composition (classic and EOMES+ Tr1-like) in the tumor microenvironment of NLPHL and more specifically, to determine cell densities of Tregs in relation with the different histopathological growth patterns of NLPHL. We hypothesize that the number of Tregs will be higher in those immunoarchitectural patterns with the higher risk of disease recurrence/progression. Patients with a diagnosis of NLPHL between 2017 and 2021 with formalin-fixed paraffin embedded tissue biopsies available in our institution were included in the study. All cases were submitted to a previously optimized and validated multiplex IF panel which was specifically developed to assess classic and EOMES+ Tr-1 like Tregs. The panel included CD3, CD4, CD8, CD20, CD25, EOMES, Foxp3, and Granzyme K. Reactive tonsils were used as a positive control. The slides were imaged using Vectra Polaris system (Akoya Biosciences, Marlborough, MA) and up to 10 representative regions of interest (ROI) were selected from each case. The data was consolidated using Spotfire software. The nonparametric Mann-Whitney test was used to compare ROI representing group I and group II histologic areas. Eleven patients with available pretreatment samples were identified. The majority were male (n=7, 63%), with advanced stage of disease (n=7, 63% Stage III/IV); all patients were alive at last follow-up (median: 42 months). A total of 109 ROIs were analyzed (n=54 in group I and n=55 in group II) with a mean number of 22,723 cells/case, and a mean analyzed area of 1.6 mm2/case. The population of CD4+ T-cells was significantly increased in group I (patterns A-C) when compared to group II (patterns D to F) (median, 640 vs 2100, p=0.0013). Interestingly, the group II was associated with a significantly higher cell density of CD4+ EOMES+ Tr1-like cells when compared to group I (median, 0 vs 1010, p<0.0001) (Figure 1). Although not statistically significant, classical Tregs (CD3+CD4+Foxp3+) were also increased in the group II (median, 24.64 vs 67.77, p=0.094). In summary, increased cell densities of Tregs and specifically EOMES+ Tr1-like are strongly associated with architectural patterns of high-risk for disease recurrence and progression in NLPHL. Our data provide a biological rational to focus on these subset populations in efforts to decrease disease recurrence and progression in NLPHL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

e19541 Background: Primary central nervous system lymphoma (PCNSL) is an aggressive and rare extranodal non-Hodgkin lymphoma with a dismal prognosis in most patients. Outcomes in Latin population is unknown. Methods: We present a retrospective cohort of fifty-five and six newly diagnosed Peruvian patients treated at the Instituto Nacional de Enfermedades Neoplasicas from 2000-2020 and at Oncosalud from 2014-2020, respectively. Inclusion criteria were (1) histologic diagnosis of diffuse large B-cell lymphoma by two pathologists; (2) disease localized exclusively in the brain, cranial nerves, meninges, or eyes; and (3) no evidence of human immunodeficiency virus infection. Results: Median age at diagnosis was 52 years old [range 21-76]. Sixty-one percent were men. Eastern Cooperative Oncology Group performance status was ≥2 in 68% of patients. Clinical presentation was characterized by intracranial hypertension symptoms (67%), focal deficit (64%), visual disturbance (18%), and seizures (9%). elevated LDH was present in 26/46 (57%) patients, multiple lesions in 19/56 (34%) patients, and involvement of deep structures 21/62 (34%) patients. Seven patients were treated by surgery only (3, subtotal and 4, total resection), three patients received radiotherapy only, and six patients did not receive any treatment. Forty-two patients received the following chemotherapy protocols: DeAngelis (26%), high-dose methotrexate (HD-MTX) (17%), HD-MTX + high-dose ARAC (HD-ARAC) (36%) and HD- MTX + HD-ARAC + Rituximab (9%), HD-MTX + Rituximab + Temozolomide (TMZ) as induction and consolidation with etoposide (VP16) + HD-ARAC (12%), the latter was used in the private center. Clinical outcomes are described in Table. The median follow-up time was 9m (0.03-248). The median overall survival (OS) was 9.9m, 5y OS was 41.7% (95% CI, 29.2-53.9). The median OS were 6.6m and 67.3m for the public and the private institution, respectively (p=0.02). 5y OS was 34% and 100% in the public and the private center, respectively. Conclusions: Peruvian patients are 15 years younger than those reported in the literature. OS in our cohort is dismal, being poorer in those patients treated at the public center reflecting treatment disparities between the public and private health system. All patients who received HD-MTX+HD-ARAC+TMZ as induction and VP16 +HD-ARAC as consolidation achieved complete response and the median OS was not reached although this can be explained due to a short follow-up time compared to those who received DeAngelis regimen. A longer follow-up is needed to demonstrate if polychemotherapy without radiotherapy is the best treatment in this group of patients.[Table: see text]

7012 Background: Acute Lymphoblastic Leukemia (ALL) in Latino countries is characterized by high incidence and worst outcomes compare to other ethnicities. However, the actual epidemiological characterization of ALL in South America remains unknown. The lack of registries, uniform treatment and prospective protocols have been pointed out for these disparities. Also, biological, and social aspects of this disease play an important role that has not been well examined. We aimed to evaluate the survival of patients with acute lymphoblastic leukemia according to demographic characteristics with emphasis in the place of residence. Methods: We performed an analytical retrospective cohort study with subjects diagnosed and treated for ALL during the period 2016-2018 at the Peruvian national cancer center (INEN, Instituto Nacional de Enfermedades Neoplasicas). INEN is currently the main center dedicated to diagnosing and treat acute leukemias for patients without social neither private insurance. Also, INEN is located at the capital city (Lima-Peru). The calculated sample size was 378 patients. Patient data were obtained from the epidemiological registry and corroborated with the national registry of mortality (RENIEC, Registro Nacional de Identificacion y Estado Civil Overall survival probabilities according to demographic characteristics were estimated using the Kaplan-Meier curve; in addition, the Log-rank test and Cox regression were used. Results: A sample of 378 patients were included during the study period (N = 588), of which 212 (56.8%) were male, 42% were between 0-10 years, 24% in 46-65 years. Regarding the characteristics at diagnosis, 80% were Ph(-) BCP-ALL and 69% corresponded to high-risk groups. At 42 months of follow-up, the median survival of the patients was 29 months (95% CI: 23.3-34.6), and the overall survival at three years was 44.8%. Overall survival in males (48.8%) was higher than in females (39.5%). According to the range of age, the highest survival was in the group of 0-10 years (70%), followed by 11-20 years (36.8%) and the lowest survival was in 46- 65 years (12.5%). Furthermore, overall survival in Lima (51.5%) was higher than in the country-side (39.7%). There was a statistically significant association (p < 0.05) between survival and sex (p = 0.042), age range (p = 0.000) and place of residence (p = 0.005); according to the Log-rank test. Conclusions: We report a lower survival among all age groups in ALL compared to international working groups. Living in a country-side region represents a significant factor for dismal survival in our cohort. Specialized health care access to diagnosis and treatment should be warranted for patients with geographical limitations and programs to ensure it must be implemented.

Background: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with dismal prognosis and associated with clonal T-cell expansion driven by Human T-Lymphotropic Virus 1 (HTLV-1) infection. Comprehensive genomic studies in Japan have identified recurrent alterations affecting TCR-NF-kB signaling (i.e. PRKCB, PLCG1, CARD11, VAV1, and IRF4), T-cell trafficking pathways (i.e. CCR4 and CCR7), and the tumor suppressor genes CDKN2A and TP53. HTLV-1 endemic regions include Africa, the Caribbean, and South America in addition to Japan. Retrospective studies from the Western population have reported distinctive features from the Japanese cohort, e.g. younger age, more common lymphomatous presentation, and worse outcomes. Our group sought to evaluate the unique molecular features of ATLL in a large cohort of patients from the Caribbean and South America.

La pandemia COVID-19 originado por el Coronavirus 2, agente causal del síndrome respiratorio agudo severo (SARS-CoV-2) ha desencadenado una crisis de salud pública a nivel global. Muchos reportes indican resultados desalentadores en pacientes con cáncer respecto a la población general. Por ello, los expertos en el manejo de neoplasias oncohematológicas del Instituto Nacional de Enfermedades Neoplásicas, hospitales nacionales y una clínica privada de Lima Metropolitana han desarrollado recomendaciones obtenidas por consenso para continuar con el manejo de pacientes con neoplasias oncohematológicas en forma segura ante la coyuntura de pandemia.

Introduction: T-cell lymphomas are a relatively rare and heterogeneous group of lymphoid neoplasms. Its incidence relies on viral infections incidence as Human T-cell lymphotropic virus type I-II (HTLV-I/II) and Ebstein Bar virus (EBV). Specifically, these viruses have a significantly higher incidence in Latin-American populations. Our objective was to calculate the incidence and survival of T-cell lymphomas in the largest Peruvian population based on a national registry. Methods: We conducted a multicenter, retrospective registry study of non-Hodgkin T cell lymphoma. The data was extracted from Instituto Nacional de Enfermedades Neoplasicas and Oncosalud-AUNA, Lima-Peru, from January 2010 to December 2019, a total of 948 patients who were diagnosed as mature T cell non-Hodgkin lymphoma based on the World Health Organization Classification 2008 were enrolled. T-lymphoblastic lymphoma/leukemia was excluded. Overall survival was calculated based on death dates from the Peruvian national identification registry (RENIEC).

Abstract Introduction Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy with multi-organ and frequent skin involvement, and poor clinical outcomes. Based on the limited available data, the estimated incidence is 0.44% of all hematologic malignancies, representing less than 1% of acute leukemias, and 0.7% of cutaneous lymphomas. Due to the rarity of this entity, there have been relatively few studies characterizing the molecular profile of BPDCN. We examined a cohort of 51 patients with BPDCN using OncoScan chromosome microarray, which provides genome-wide copy number abnormality (CNA) analysis. Methods An international cohort of BPDCN cases were collected from centers in Brazil (Laboratorio de Patologia, Botucatu), Swtizerland (University of Zurich), France (Hospital St. Louis, Paris), Peru (Instituto Nacional de Enfermedades Neoplasicas, Lima), Canada (Department of Pathology, University of Montreal), Italy (Derpartment of Pathology, University of Bologna), and US (Department of Pathology - The Ohio State University, Department of Hematopathology - MD Anderson Cancer Center; and Department of Pathology - University of Virginia). A total of 58 tissue blocks from 51 patient samples were retrieved. The diagnosis of BPDCN was done and confirmed by at least three independent hematopathologists or dermatopathologists in accordance with the WHO classification (Lyon 2017). For the purpose of the molecular analysis substratification, cases were classified as 'BPDCN' if they were positive for TCF4, and 'BPDCN-like' if they were negative for TCF4. Immunohistochemistry for CD123, CD4, and CD56 was performed in all cases. Exclusion criteria included expression of MPO, lysozyme, CD3, CD19, CD20, CD22, and/or EBV. DNA was extracted from FFPE samples via standard techniques and processed on OncoScan CNV Plus microarray (ThermoFisher Scientific) according to manufacturer's recommended protocol. Copy number abnormalities and select single nucleotide variants and insertions/deletions (74 mutations in 9 genes) were analyzed on Chromosome Analysis Suite software (ChAS v4.1; ThermoFisher Scientific). Additional analysis was performed using Nexus Copy Number (BioDiscovery, version 10.0). Results To date, we have successfully analyzed 45 cases of BPDCN with Oncoscan, revealing widespread CNA in the vast majority of cases (44/45; 98%). Alterations of chromosome 9 were common in this cohort, particularly CNAs involving CDKN2A/B at 9p21.3. Twenty-five cases (56%) demonstrated CNA including CDKN2A/B, with ten of these cases demonstrating a homozygous loss of CDKN2A/B (22%). Alterations of chromosome 13 were also frequently detected with loss of RB1 (located at 13q14.2) detected in 24 cases (53%). The RUNX1 gene (21q22.12) was a common target of CNAs in this cohort, seen in nine cases (20%). Eight of these cases showed a copy number gain of RUNX1, which is a recurrent finding in a variety of hematological malignancies, particularly myeloid neoplasms. The remaining case with RUNX1 CNA showed a focal, homozygous loss of the gene, demonstrating that dysregulation of RUNX1 through CNA is a common event in BPDCN. We observed frequent deletions of ETV6 (53%), IKZF1 (33%), and TP53(16%) in our cohort. The ARHGAP26 gene (5q31.3), which is associated primarily with juvenile myelomonocytic leukemia, was included in CNA in 13 cases (29%), with both gains and losses observed in this cohort. Oncoscan can detect a limited number of single nucleotide variants in nine genes that are frequently mutated in cancers (BRAF, EGFR, IDH1, IDH2, KRAS, NRAS, PIK3CA, PTEN, and TP53). Mutations were detected in ten cases (22%), with NRAS and TP53 variants detected in three cases each and KRAS and IDH2 variants detected in two cases each. Conclusions Our preliminary data demonstrates complex genomic alterations in BPDCN, with the RB1 locus on chromosome 13, the CDKN2A/B locus on chromosome 9, and the ETV6 locus on chromosome 12 most commonly detected. However, widespread genomic alterations were detected involving a variety of cancer-associated genes further characterizing CNA in BPDCN. Analysis of additional BPDCN cases is progress. Disclosures Khoury: Kiromic: Research Funding; Angle: Research Funding; Stemline Therapeutics: Research Funding. Porcu: Viracta: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Daiichi: Honoraria, Research Funding; Kiowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Spectrum: Consultancy; DrenBio: Consultancy. Gru: StemLine: Honoraria, Research Funding, Speakers Bureau; CRISPT Therapeutics: Research Funding; Innate Pharma: Research Funding.