Abstract: INTRODUCTION: Adult T-cell leukemia/lymphoma (ATLL) is a mature peripheral T-cell neoplasm caused by the Human T-cell Leukemia Virus Type 1 (HTLV-1). HTLV-1 infects up to 10 million people worldwide and is most endemic in Southwestern Japan, the Caribbean basin, South America, and Western Africa. In Latin America (LA), Peru and Brazil have the highest prevalence of HTLV-1-related diseases, however, data on ATLL in other LA countries is scarce. ATLL carries a dismal prognosis and is essentially incurable by conventional drugs. We describe the epidemiology, clinical features, treatment, and disease outcome of ATLL encountered in 11 countries in LA. METHODS: We retrospectively analyzed patients (pts) diagnosed with ATLL between January 1995 and December 2019. ATLL cases were classified according to the Shimoyama criteria into acute (A), lymphomatous (L), chronic (C) and smoldering (S). Treatment approaches used as first-line therapy were: 1) chemotherapy alone; 2) combined chemotherapy with zidovudine/interferon-alpha (AZT-IFN); and 3) AZT-IFN alone, as previously done with Miami cohort (Malpica and Ramos et al. Blood Advances 2018). Treatment response was assessed according to Tsukasaki et al. (JCO 2009) criteria. To be classified as complete response (CR), partial response and stable disease, these had to persist for a period of at least 4 weeks. Survival curves were estimated using the Kaplan-Meier method and Log rank test. RESULTS: A total of 253 pts with ATLL were identified. Two hundred twenty six pts (L=122, A=73, C=26, S=5) had sufficient data for analysis. Demographic and clinical features are shown in Figure 1 and Table 1. Median age at diagnosis was 57 years, with a female predominance in A (58%) and S (100%) types. Most ATLL pts were from Peru (n=159, 63%) followed by Chile (n=44, 17%), Argentina (n=20, 8%) and Colombia (n=17, 7%). B symptoms were high present in A, L and C types (73%, 72%, 58% vs. 8% S type, respectively, p=0.011). Hypercalcemia was highly associated with A type (57% vs. L 27%, p=0.014). The PIT score yielded to a more aggressive risk classification compared to the IPI score (high-risk: 55% vs. 29%, respectively, p & lt;0.001). Strongyloidiasis (n=5) and pneumocystis jirovecii pneumonia (n=5) were the most commonly observed co-infections at diagnosis. Commonly affected extranodal sites other than bone marrow in all subtypes were skin 25% (n=63) and liver 9% (n=24). The therapy approach used during the first 2 therapy evaluations are summarized in Table 2. The median survival (MS) times were 4.3 months, 7.9 months, 21.1 months, and not reached for A, L, C and S form, with 4-year survival of 8%, 22%, 40% and 80%, respectively (Figure 2). First-line AZT-IFN resulted in overall response (OR) rate of 63% (CR 24%) for A (n=8) and 75% (CR 50%) for L (n=8), respectively (Table 3). The OR rates after first-line multi-agent chemotherapy alone for A vs. L were 21% (CR 8%) and 41% (CR 29%), respectively (Table 3). The most commonly used regimens were CHOP/CHOP-like (n=117, 59%) and CHOEP (n=40, 20%) regimens with OR rates of 29% (CR 12%) and 60% (CR 42%), respectively (Table 3). Progression-free survival (PFS) rates in pts with aggressive ATLL who achieved CR after chemotherapy vs. AZT-IFN (alone or in combination with chemotherapy) were 2.8 months vs. 30.4 months for A (n=8) type and 67.1 months vs. 17.7 months for L (n=30) type, respectively (Figure 3). Only 2 pts with L type underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) with PFS of 12 and 17 months (Table 4). CONCLUSION: ATLL continues to carry a dismal outcome with conventional therapies thus urging the development of novel approaches. Our study found that Latin American ATLL variant presents at a younger age, has a female predominance, high incidence of L type, low incidence of indolent types and lower survival rates, suggesting that Latin American ATLL variant presents earlier and more aggressively than in Japanese pts. AZT-IFN produced durable responses in A type patients who achieved CR as compared to chemotherapy alone. Chemotherapy responses were more durable in L types who achieved CR as compared to A type. In conclusion, in the management of aggressive ATLL, chemotherapy remains the preferred choice for L type (with consideration of allo-HSCT upfront), while AZT-IFN is a good option to attempt for A type upfront. Figure Disclosures Peña: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; BindingSite: Research Funding. Idrobo:Amgen: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau. Altamirano:Hospital Nacional Guillermo Almenara Irigoyen: Other: Servicio de Hematologia. Perini:Abbvie: Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria. Castillo:Janssen: Consultancy, Research Funding; Abbvie: Research Funding; TG Therapeutics: Research Funding; Kymera: Consultancy; Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding. Ramos:NIH: Research Funding. Villela:Roche: Other: advisory board, Speakers Bureau; amgen: Speakers Bureau.

Abstract: Background : Adult T-cell leukemia/lymphoma (ATLL) is an aggressive, peripheral T-cell neoplasm associated with the human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 infects up to 10 million people worldwide and is most endemic in Southwestern Japan, the Caribbean basin, South America and Western Africa. In Latin America, highest prevalence is found in Haiti, Jamaica, Dominican Republic, Brazil and Peru. ATLL has a poor prognosis, with shorter overall survival (OS) relative to other peripheral T-cell lymphomas. Although current prognostic models require extensive radiologic and laboratory investigations, oftentimes they are not readily available in most Latin American countries, hence, a simple prognostic model is useful. We aim to identify and then validate a simple clinical prognostic model for ATLL in the Latin American population by analyzing clinical parameters and only laboratory tests that are widely available across Latin American countries. Patients and Methods : We retrospectively analyzed patients (pts) diagnosed with ATLL between January 1987 and December 2018. Aggressive ATLL cases were classified according to the Shimoyama criteria into acute (A) and lymphomatous (L). Cox regression modeling was performed on several clinical and laboratory parameters in two independent cohorts: first, a learning cohort (LC) of ATLL pts diagnosed and managed at two tertiary hospitals in Chile and Peru, and then a cohort of ATLL pts from a tertiary hospital in Miami was used to validate the model (validation cohort, VC). OS curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional-hazard regression models were fitted. Results : A total of 149 pts (A=55, L=94) in the LC, and 101 pts (A=58, L=43) in the VC were identified, with 101 and 94 pts receiving therapy in each cohort, respectively. Clinical features are shown in Table 1. In both cohorts, there was a young ( 〈 60 years, LC=51%, VC=64%), and female predominance (LC=52%, VC=61%). Pts in the LC had a better performance status compared to the VC (ECOG ≥2, LC=50% vs. VC=76%). Pts in the VC had advanced stages of disease (stage III/IV, LC=88% vs. VC=97%), and ≥1 extranodal involvement (LC=17% vs. VC=76%) compared to the LC. High LDH, low serum albumin ( 〈 3.5 g/dL), bone marrow involvement and anemia (hemoglobin 〈 10 g/dL) were no different in both cohorts. The calculated International Prognostic Index (IPI) and Prognostic Index for T-cell lymphoma (PTI) scores are presented in Table 1. Most pts in the VC had high risk IPI and PIT scores (High risk: IPI LC=21% vs. VC=62%; PIT LC=38% vs. VC=51%) compared to the LC that had more low and low/intermediate IPI and PIT scores (Low risk: IPI LC=13% vs. VC=0%; PIT LC=5% vs. VC=0%; Low/intermediate risk: IPI LC=26% vs. VC=7%; PIT LC=23% vs. VC=16%). The median OS was 6 and 8.4 months in the LC and VC, respectively (Figure 1). In the univariate and multivariate analysis, ECOG ≥2 and serum albumin 〈 3.5 g/dL were both associated with a worse OS (Table 2). When adjusted to IPI and PIT scores, serum albumin 〈 3.5 g/dL was a negative prognostic factor, independent of IPI score, and a trend in PIT score, in the LC (adjusted for IPI: HR 1.71, 95% CI 1.06-2.75; p=0.03 / PIT: HR 1.56, 95% CI 0.95-2.56; p=0.07), but independent prognostic factor from both, IPI and PIT scores, in the VC (adjusted for IPI: HR 2.45, 95% CI 1.41-4.24; p=0.001 / PIT: HR 2.43, 95% CI 1.44-4.08; p=0.001) (Figure 2). Comparable results were found when investigating by ATLL subtype, with results trending towards significance for OS, IPI and PIT scores in the LC, but then validated in the VC (Figure 3). Conclusions : To the best of our knowledge, this is the largest retrospective study evaluating the clinical features of HTLV-1 related ATLL and impact on disease outcome in Latin America. We have validated a simple prognostic model in pts with aggressive ATLL. Our results suggest that a serum albumin level of less than 3.5 g/dL is a reliable, and independent prognostic factor for survival in aggressive ATLL. This prognostic model could be used to complement or modify existing and widely used international prognostic indexes for lymphoma. This simple paradigm could be useful in validating treatment outcomes after chemotherapy or highly needed new approaches for ATLL in prospective studies, particularly in developing countries where the absence of sophisticated laboratory and imaging tests hinder treatment decisions. Disclosures Peña: Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Janssen: Other: Congress inscription and flights; Pfizer: Membership on an entity's Board of Directors or advisory committees. Rojas:Pfizer: Membership on an entity's Board of Directors or advisory committees; ABBVIE: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; ROCHE: Membership on an entity's Board of Directors or advisory committees. Paredes:Tecnofarma: Honoraria. Abello:Takeda: Other: Participation in advisory board meeting. M:Merck-Sharp-Dome: Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Roche-Mexico: Consultancy, Speakers Bureau.

Abstract: Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma subtype seen in Western countries. However, data on FL from Latin America (LATAM) are scarce. We aimed at better understanding the clinical features, treatment patterns and outcomes of patients with FL from LATAM. Methods: This is a retrospective study that included all consecutive patients with a pathological diagnosis of FL at 18 participating centers from 12 LATAM countries. All cases were reviewed by specialized pathologists at their respective participating centers. Pertinent clinical, pathological and treatment data were collected. Responses were assessed per the Lugano criteria. Time to first treatment, progression-free survival after first treatment (PFS1) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: A total of 763 patients were included in this analysis. On clinical features, 51% of patients were ≥60 years, 46% were male, 29% had extranodal involvement, 27% had bulky disease (≥6 cm in diameter), 68% had stage III/IV disease, 21% had hemoglobin & lt;12 g/dl, 12% had serum albumin & lt;3 g/dl, 34% had elevated serum LDH and 24% had B2-microglobulin ≥3,5 mg/l. Low, intermediate and high-risk FLIPI was seen in 43%, 33% and 23% of patients, respectively. Low, intermediate and high-risk FLIPI2 was seen in 18%, 64% and 17% of patients, respectively. The median time to first treatment was 0.08 years (95% CI 0.08-0.09), and 88% of patients started therapy within 1 year of diagnosis. Of the 647 treated patients, 70% received CHOP ± rituximab (R), 16% CVP ± R, 6% bendamustine ± R, 4% R alone and 4% other treatments. Response data were available in 628 patients with complete response in 72%, partial response in 21% and no response in 7%, for an overall response rate of 93%. The median PFS1 was 10.5 years (95% CI 7.3-not reached; Figure), and 74 patients (12%) had disease progression within 24 months of first treatment initiation (POD24). The median OS was 21.1 years (95% CI 13-not reached; Figure). Patients with low, intermediate and high FLIPI had median OS not reached, 21.1 and 9.5 years, respectively (p & lt;0.001). Patients with low, intermediate and high FLIPI2 had median OS not reached, 21.1 and 6.8 years, respectively (p & lt;0.001). Patients who had and did not have POD24 had median OS of 7.3 years (95% CI 4.8-not reached) and 21.1 years (95% CI 13-not reached), respectively (p & lt;0.001). Conclusion: This large, real world evidence LATAM cohort of 763 patients with FL showed a higher than expected female incidence as well as higher rates of extranodal and bulky disease than previously reported in Western cohorts. Chemoimmunotherapy is the standard approach to FL patients in LATAM, which is associated with high rates of response and highly encouraging PFS and OS rates. Our study validates the prognostic value of FLIPI, FLIPI2 and POD24. Figure Disclosures Villela: Roche: Other: advisory board, Speakers Bureau; amgen: Speakers Bureau. Peña:Amgen: Speakers Bureau; BindingSite: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Idrobo:Takeda: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau. Abello:Dr. Reddy's: Consultancy, Research Funding; Takeda: Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding. Perini:AbbVie, Janssen: Speakers Bureau; Janssen, Takeda: Honoraria. Castillo:Abbvie: Research Funding; Janssen: Consultancy, Research Funding; Kymera: Consultancy; TG Therapeutics: Research Funding; Beigene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding.

Abstract: Introduction: Peripheral T cell lymphoma (PTCL) is a very heterogenous disease and corresponds to approximately 15% of all non-Hodgkin lymphoma cases. PTCL is divided into several subtypes, however, PTCL not otherwise specified (PTCL-NOS) is the most frequent, with a proportion of 26% of all PTCL cases. There is a lack of demographic and clinical data about PTCL-NOS in middle- and low-income countries, where patients' access to early diagnosis and otherwise standard care might be suboptimal. The objective of this study is to describe the population of PTCL-NOS patients in Latin America, specifically from the countries conforming the "Grupo Latinoamericano de Linfomas" (GELL), in order to better understand clinical behavior and find possible prognostic factors that might prognosticate overall survival (OS). We specifically evaluated the neutrophil/lymphocyte ratio (NLR) and serum albumin as potential prognostic factors. Methods: An observational, retrospective and analytical study was conducted during the period from January 2000 through January 2018. A total of 200 Latin American patients with a pathological diagnosis of PTCL-NOS were included. Clinical data were gathered from clinical records. NLR ≥4 and serum albumin ≤3.5 g/dl were considered adverse prognostic factors. Median Overall Survival (mOS) and 5-year Overall Survival (5y-OS) rates were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional-hazard regression analyses were performed to identify adverse prognostic factors for OS. Data were analyzed and interpreted using STATA 15. Results: A total of 200 patients with a diagnosis of PTCL-NOS were included. 50% of patients were ≥60 years, 57% were male, 50% had ECOG ≥2, 40% had elevated serum Lactate Dehydrogenase (LDH) level, 70% showed stage III/IV disease, bone marrow involvement was present in 37% of patients, B symptoms in 65%, 33% presented with hemoglobin levels 〈 10 g/dL. The International Prognostic Index (IPI) score was high-intermediate in 33% and high in 14% of cases. The Prognostic Index for PTCL-U (PIT) risk score was high-intermediate in 32% and high in 26% of cases. Serum albumin 〈 3.5 mg/dl was seen in 58%, and NLR ≥4 in 37% of patients. Median OS (mOS) for the entire cohort was 0.83 years (95% CI 0.58-1.75) and 5-year OS rate was 31% (95% CI 23-40%). Patients with serum albumin levels 〈 3.5 g/dL had mOS of 0.42 years (95% CI 0.25-0.75) and 5-year OS rate of 20% (95% CI 9-33%), while patients with albumin ≥3.5 g/dL had mOS of 5.1 years (95% CI 0.83-not reached) and 5-year OS rate of 51% (95% CI 36-65%) (log-rank p 〈 0.001). The mOS for NLR 〈 4 was 1.67 years (95% CI 0.75-4.92) with 5-year OS rate of 37% (95% CI 25-48%) while for NLR ≥4, the mOS was 0.58 years (95% CI 0.25-1.00) and 5-year OS rate was 23% (95% CI 12-36%) (log-rank p=0.02). Cox proportional Hazard regression multivariate analyses found serum albumin 〈 3.5 g/dL (HR 1.83, 95% CI 1.10-3.05; p=0.02) and ECOG ≥2 (HR 1.95, 95% CI 1.15-3.30; p=0,01) were associated with a worse OS. Serum albumin remained an adverse prognostic factor for OS after adjustment for the IPI and the PIT scores (HR 1.66, 95% CI 1.01-2.75; p=0.047, and HR 1.70, 95% CI 1.03-2.80; p=0.038, respectively). Conclusion: This multi-institutional Latin American study showed that serum albumin level 〈 3.5 g/dL was an adverse prognostic factor for OS, independent from the IPI and the PIT scores, in Latin American patients with a diagnosis of PTCL-NOS. The survival rates of Latin American patients with PTCL-NOS appear lower than in developed countries. Disclosures M: Merck-Sharp-Dome: Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Roche-Mexico: Consultancy, Speakers Bureau. Peña:Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Janssen: Other: Congress inscription and flights; Pfizer: Membership on an entity's Board of Directors or advisory committees. Paredes:Tecnofarma: Honoraria. Rojas:ROCHE: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; ABBVIE: Membership on an entity's Board of Directors or advisory committees. Abello:Takeda: Other: Participation in advisory board meeting. Castillo:Abbvie: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; TG Therapeutics: Research Funding.

Abstract: INTRODUCTION: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell neoplasm caused by the Human T-cell Leukemia Virus Type 1 (HTLV-1). HTLV-1 infects up to 10 million people worldwide and is most endemic in Southwestern Japan, Western Africa, the Caribbean basin and South America. Cutaneous signs of ATLL are varied and may consist of macules (M), plaques (P), multiple papules (MP), tumoral nodules (TN), erythroderma (E) or mixed-lesions (≥2 predominant lesions, ML). M and P forms are believed to carry a better prognosis. However, data on cutaneous presentation of ATLL remains scarce. Herein, we report cases of ATLL with cutaneous involvement diagnosed in 4 Latin American countries over the last 3 decades. METHODS: We retrospectively analyzed patients (pts) diagnosed with ATLL between January 1995 and December 2019. ATLL subtypes were classified according to the Shimoyama criteria into acute, lymphomatous, chronic and smoldering. Primary cutaneous tumoral (PCT) variant was classified according to the 2019 International Revised ATLL Consensus. We designed 2 cohorts: the first, ATLL pts with cutaneous involvement, and the second, matched cases without cutaneous involvement. We determined the type of skin lesion as well as the survival associated with the various types of skin lesions. We compared the frequency of clinical features using Fisher's exact test. Treatment response was assessed according to Tsukasaki et al. (JCO 2009) criteria. To be classified as complete response (CR), partial response, and stable disease, these had to persist for a period of at least 4 weeks. We analyzed survival data according to ATLL subtype, cutaneous involvement status, and type of skin lesion using the Kaplan-Meier method and Log rank test. RESULTS: A total of 169 pts with ATLL were identified; 63 had cutaneous involvement and 106 did not. Clinical features are shown in Table 1. In both groups the median age was 57 years with a female predominance. Cutaneous involvement was most frequently found in acute (41%) and lymphomatous (37%) ATLL pts. The E (24%) and P (22 %) types were the most frequent skin lesions. Disease stage, presence of B symptoms, hypercalcemia, ECOG ≥2, elevated LDH, and IPI/ PIT score were not different among groups. Table 2 and Table 3 summarize the first-line therapy used and response rates. The use of first-line zidovudine plus interferon alpha (AZT-IFN), regardless of the type of skin lesion, resulted in relatively high response rates [overall response (OR) 100%, n=8; CR 62.5%] as compared to multi agent-chemotherapy (OR 33.3%, n=12). Overall, the presence of cutaneous involvement was associated with better overall survival (OS) compared to non-cutaneous involvement (aHR 0.55 [95% CI: 0.37-0.82] , p & lt;0.01; 1-year OS 53% vs. 27%, respectively, p=0.012) (Figure 1). PCT pts had better outcome compared to acute and lymphomatous ATLL forms (1-year OS 75% vs. 39% vs. 25%, respectively, p=0.002). The presence of P and MP skin lesions was associated with better OS compared to other subtypes (1-year OS: P/MP 65% vs. others 41%, respectively, p=0.027) (Figure 2, supplemental figure 1). In a multivariate analysis, hypercalcemia was an independent poor prognostic factor for survival among ATLL pts with cutaneous involvement (aHR 3.99 [95% CI: 139-11.45], p=0.01) (supplemental figure 2). One patient with lymphomatous ATLL and plaque lesions underwent allogeneic stem cell transplant with high-dose chemotherapy after achieving CR with AZT-IFN; patient remains alive and progression-free for 17 months. Illustrative cases of cutaneous ATLL are shown in Figure 3. CONCLUSION: In Latin American pts with aggressive ATLL, cutaneous involvement appears to be associated with better survival compared to non-cutaneous involvement. PCT subtype, an ATLL variant characterized by isolated skin lesions with no organ involvement and poor outcome, appeared to have a better prognosis compared to acute and lymphomatous ATLL forms. P and MP skin lesions were both associated with better survival. Hypercalcemia was found as an independent prognostic factor for survival in pts with cutaneous involvement. Finally, AZT-IFN appears to be reasonable first-line option for aggressive ATLL subtypes with cutaneous involvement regardless of the type of skin lesion at diagnosis, based on the relatively high response rates observed in this subset; further investigation in randomized clinical trials is needed. Disclosures Peña: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; BindingSite: Research Funding. Idrobo:Takeda: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Altamirano:Hospital Nacional Guillermo Almenara Irigoyen: Other: Servicio de Hematologia. Perini:Abbvie: Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria. Castillo:Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Abbvie: Research Funding; Kymera: Consultancy; TG Therapeutics: Research Funding; Janssen: Consultancy, Research Funding. Ramos:NIH: Research Funding. Villela:amgen: Speakers Bureau; Roche: Other: advisory board, Speakers Bureau.

Abstract: Introduction: Diffuse Large B-Cell Lymphoma (DLBCL) is the most frequent subtype of high-grade lymphoma in Latin American patients. The neutrophil-to-lymphocyte ratio (NLR) has shown to be prognostic in patients with DLBCL in Asia, Europe, and the United States. We previously reported that NLR ≥4 was an adverse prognostic factor for overall survival (OS) in DLBCL patients treated with chemoimmunotherapy. We aim to assess the prognostic and predictive role of NLR ≥4 in a learning cohort of DLBCL patients from South America and confirm the findings in a validation cohort of DLBCL patients from Mexico. Methods: The study period was from January 2002 through January 2018, and included patients with de novo DLBCL treated with standard chemoimmunotherapy with a curative intent. A cohort of patients from South America (Peru, Argentina, Venezuela, Chile and Colombia) was the learning cohort, a cohort of patients from Mexico was the validation cohort. Univariate and multivariate logistic regression analysis and Cox proportional-hazard regression models were fitted for complete response (CR) as well as for OS in the learning cohort and the validation cohort, separately. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: A total of 597 patients with a diagnosis of DLBCL were included. The learning cohort included 274 patients, and the validation cohort included 323 patients. In the learning cohort, CR rates for DLBCL patients with NLR ≥4 and NLR 〈 4 were 62% and 78%, respectively (p=0.003). In the multivariate analyses for CR, advanced stage and NLR ≥4 were associated with lower odds of CR (OR 0.39, 95% CI 0.21-0.70, p=0.002; and OR 0.46, 95% CI 0.27-1.63, p=0.006, respectively). NLR ≥4 was independently associated with lower rates of CR when adjusted for the IPI and the NCCN-IPI scores (OR 0.46, 95% CI 0.27-0.79, p=0.005; and OR 0.47,95% CI 0.28-0.81, p=0.006, respectively). The 5-year OS rates for DLBCL patients with NLR ≥4 was 58% versus 70% for patients with NLR 〈 4. In the multivariate analyses for OS, advanced stage (HR 2.47, 95% CI 1.55-3.93; p 〈 0.001) and NLR ≥4 (HR 1.55, 95% CI 1.20-2.36; p=0.04) were statistically significant factors associated with worse OS. NLR ≥4 was an adverse prognostic factor after adjusting for the IPI and the NCCN-IPI scores (HR 1.50, 95% CI 1.01-2.28; p=0.04; and HR 1.47, 95% CI 1.01-2.21; p=0.04, respectively). In the validation cohort, CR rates for DLBCL patients with NLR ≥4 and NLR 〈 4 were 64% and 81%, respectively (p=0.001). In the multivariate analyses for CR, elevated LDH level and NLR ≥4 were associated with lower odds of CR (OR 0.53, 95% CI 0.29-0.97, p=0.04; and OR 0.49, 95% CI 0.27-0.88, p=0.01, respectively). NLR ≥4 was independently associated with lower rates of CR when adjusted for IPI score and the NCCN-IPI score (OR 0.46,95% CI 0.26-0.82, p=0.008; and OR 0.46, 95% CI 0.25-0.81, p=0.007, respectively). The 5-year OS rates for DLBCL patients with NLR ≥4 was 48% versus 68% for patients with an NLR 〈 4. In the multivariate analysis for OS; ECOG ≥1 (HR 1.85, 95% CI 1.24-2.77; p 〈 0.003), advanced stage (HR 2.04, 95% CI 1.28-3.26, p=0.003) and NLR ≥4 (HR 1.80, 95% CI 1.22-2.65; p=0.03) were independent factors associated with worse OS. NLR ≥4 was an adverse prognostic factor after adjusting for IPI score and NCCN-IPI score (HR 1.81, 95% CI 1.24-2.64; p=0.002; and HR 1.96, 95% CI 1.34-2.86; p=0.001, respectively). Conclusion: This multi-institutional collaborative study identifies and validates an easy-to-use tool, NLR ≥4, as an independent factor predictive of lower rates of CR and prognostic of worse survival, independent of the IPI and the NCCN-IPI scores, in Latin-American patients with DLBCL treated with standard chemoimmunotherapy. Disclosures M: Roche-Mexico: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Merck-Sharp-Dome: Speakers Bureau. Peña:Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Janssen: Other: Congress inscription and flights; Pfizer: Membership on an entity's Board of Directors or advisory committees. Rojas:Pfizer: Membership on an entity's Board of Directors or advisory committees; ABBVIE: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; ROCHE: Membership on an entity's Board of Directors or advisory committees. Paredes:Tecnofarma: Honoraria. Ramirez-Ibarguen:Roche-Mexico: Consultancy, Speakers Bureau. Gomez-Almaguer:Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Castillo:Pharmacyclics: Consultancy, Research Funding; Abbvie: Research Funding; Beigene: Consultancy, Research Funding; TG Therapeutics: Research Funding; Janssen: Consultancy, Research Funding.

Abstract: The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine × lactate dehydrogenase [LDH])/platelets] , is a marker of endothelial activation that has been validated in the allogeneic hematopoietic stem cell transplant setting. Endothelial activation is one of the mechanisms driving immune-mediated toxicities in patients treated with chimeric antigen receptor-T (CAR-T)-cell therapy. This study’s objective was to evaluate the association between EASIX and other laboratory parameters collected before lymphodepletion and the subsequent onset of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) those patients. Toxicity data were collected prospectively on 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma (LBCL). CRS grades 2 to 4 were diagnosed in 81 (47%) patients and ICANS grades 2 to 4 in 84 (49%). EASIX combined with ferritin (EASIX-F) identified 3 risk groups with CRS grades 2 to 4 cumulative incidence of 74% (hazards ratio [HR], 4.8; 95% confidence interval [CI] , 2.1-11; P & lt; .001), 49% (HR, 2.3; 95% CI, 1.02-5; P = .04), and 23% (reference), respectively. EASIX combined with CRP and ferritin (EASIX-FC) identified 3 risk groups with an ICANS grade 2 to 4 cumulative incidence of 74% (HR, 3.6; 95% CI, 1.9-6.9; P & lt; .001), 51% (HR, 2.1; 95% CI, 1.1-3.9; P = .025), and 29% (reference). Our results indicate that common laboratory parameters before lymphodepletion correlate with CAR-T–related toxicities and can help support clinical decisions, such as preemptive toxicity management, hospitalization length, and proper setting for CAR-T administration.

Abstract: Introduction. There are different scoring systems to differentiate risk groups in patients with DLBCL treated with chemoimmunotherapy. Those systems have used the same 5 variables (age, performance status, LDH, stage, extranodal involvement) for 27 years. However, LATAM data have not been included in the development of previous scoring systems. It is important to mention that novel biological variables, such as albumin, beta-2-microglobulin (B2M) and platelet/lymphocyte ratio (PLR), have been reported and could improve discrimination (Villela et al. Blood 2019; 134Suppl_1: 1613). Therefore, we carried out a large, multinational study to develop and validate a LATAM-IPI score. Methods. This is a retrospective cohort of 1030 patients with a diagnosis of DLBCL treated with standard chemoimmunotherapy with curative intent between 2010 and 2018. Data were obtained from 8 LATAM countries: Argentina, Colombia, Chile, Guatemala, Mexico, Paraguay, Peru, and Venezuela. The five classic IPI variables (age, ECOG, extranodal involvement, LDH, stage) were analyzed and albumin and PLR were added (Villela et al. Blood 2019; 134Suppl_1: 1613). B2M was not included because it was not requested regularly in all countries. Development of LATAM-IPI: The training set consisted of 85% of the sample, randomly selected, and the remaining 15% was reserved for internal validation. Using the training set, the univariate and multivariate association between clinical prognostic factors and OS was analyzed fitting Cox proportional-hazard models. Outcomes. Clinical characteristics of the training (n=878) and internal validation (n=151) cohorts are shown in Table 1. There were no statistical differences in baseline characteristics between the cohorts. The median follow-up for the whole cohort was 36 months (IQR: 11-57). When exploring the classic IPI variables on the training set, all variables were associated with high risk of mortality [age 65-74, Hazard Ratio (HR) 1.24, 95% CI 0.96 to 1.58, p=0.08; age ≥75, HR 1.71, 95% CI 1.28 to 2.28, p=0.0003), ECOG (≥ 2, HR=2, 95% CI 1.61 to 2.53; p & lt;0.0001), EN (≥2, HR=1.53, 95% CI 1.18 to 1.97; p=0.0012), stage (III/IV, HR=2.1, 95% CI 1.64 to 2.69; p & lt;0.0001) and LDH (ratio 1.1-2.9, HR=1.55, 95% CI 1.22 to 1.97; p=0.0003; ratio ≥3, HR= 2.68, 95% CI 1.93 to 3.7, p & lt;0.0001). Similarly, the biological variables Albumin (≤3.5 mg/dL, HR 2.37, 95% CI 1.9 to 2.95, p & lt;0.0001) and PLR (≥273, HR= 1.52, 95% CI 1.23 to 1.87; p=0.0001) were associated with high risk of death. Next, these variables were evaluated by multivariate analysis. The independent variables were albumin ( & lt;3.5 mg/dL, HR 1.84, 95% CI 1.45 to 2.3, p & lt;0.0001, 1 point), LDH (ratio 1.1 to 2.9, HR 1.30, 95% CI 1.02 to 1.67, p=0.03, 1 point; ratio ≥3, HR=1.84, 95% CI 1.31 to 2.5, p=0.0004, 2 points), advanced stage (HR 1.65, 95% CI 1.27 to 2.13, p=0.0001, 1 point), age (≥75, HR= 1.51, 95% CI 1.15 to 1.98, p=0.003, 1 point), and ECOG (≥2, HR 1.40, 95% CI 1.10 to 1.77, p=0.005). Now, for the development of LATAM-IPI, the groups were distributed as follows: 0 points, low; 1-3 points, intermediate; 4-6 points, high risk. There were no differences in the distribution of the risk groups between training and validation sets (Table 2). In the learning cohort, the 5-year OS rates for low, intermediate and high risk were 81%, 63% and 33%, respectively (p & lt;0.0001). In the validation cohort, the 5-year OS rates for low, intermediate and high risk were 81%, 63% and 44%, respectively (p=0.02) (Figure 1). Conclusions: Using multinational learning and validation cohorts including over 1,000 DLBCL patients treated with standard chemoimmunotherapy in LATAM, we developed a novel LATAM-IPI score using age ≥75 years, ECOG ≥2, advanced stage, LDH ratio (1.1-29 and ≥3) and albumin & lt;3.5 mg/dl. Next steps are to disseminate our results with other involved researchers in LATAM to prospectively assess and reproduce our results. We expect this score will help to further define the prognosis of DLBCL patients in LATAM. Disclosures Villela: amgen: Speakers Bureau; Roche: Other: advisory board, Speakers Bureau. Idrobo:Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Gomez-Almaguer:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Castillo:Janssen: Consultancy, Research Funding; TG Therapeutics: Research Funding; Kymera: Consultancy; Abbvie: Research Funding; Beigene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding.