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  • American Society of Hematology  (9)
  • Valvert, Fabiola  (9)
  • 1
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 18-21
    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.
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    Publisher: American Society of Hematology
    Publication Date: 2020
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  • 2
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 20-23
    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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
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  • 3
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 12-13
    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.
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    Publisher: American Society of Hematology
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  • 4
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 6708-6710
    Type of Medium: Online Resource
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    Publisher: American Society of Hematology
    Publication Date: 2022
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  • 5
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 25-27
    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.
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    Language: English
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    Publication Date: 2020
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  • 6
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2520-2520
    Abstract: Updated analysis confirms sustained poor prognosis of COVID-19 in patients with lymphoma in Latin America: A cohort of 160 patients from GELL. Introduction: Ongoing SARS-COV-2 pandemic has impacted the management of cancer patients worldwide. Several reports have demonstrated inferior outcomes of patients with hematological malignancies, including higher rates of intensive care unit admission, need for mechanical ventilation and death. The impact of COVID-19 is profound in resource-restricted countries, including Latin America. Most cohorts reported have not included patients from Latin America, and there is paucity of data of the outcome of cancer patients with COVID-19 in low- and middle-income countries. Grupo de Estudio De Linfoproliferativos En Latino-America (GELL )is a collaborative network of hematological centers in 13 countries in Latin America. We report updated outcomes of lymphoma patients diagnosed with COVID-19 in Latin America. Methods: We conducted a retrospective study including patients with a diagnosis of lymphoma and COVID-19 infection. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma were excluded from the analysis We defined active disease as follow: (1) patients with detectable disease either prior to initiating therapy or upon relapse, and/or (2) patients undergoing active cancer treatment. The primary outcome was overall survival at 100 days. Survival curves were estimated using the Kaplan Meier method. Uni and multivariable analysis were carried out with Cox model. Results: A total of 160 patients were available for analysis. Median age was 60 years old. Hypertension was the most common comorbidity (33%). Most patients had aggressive lymphomas (62%), including 43% of patients with diffuse large B-Cell lymphoma (DLBCL). Follicular lymphomas were observed in 13% of patients and Hodgkin lymphoma in 12.5% of patients. With a median follow-up of 37 days, the 100-day OS was 64% (95CI 56-74%, fig. 1). In univariate analysis, age (HR 1.03, p=0.0025), hypertension (HR 2.01, p=0.017), & gt;1 number of prior lines (HR 2.78, p=0.011), patients currently on treatment (HR 1.83, p=0.043), ferritin & gt;2000 ng/mL (HR 4.74 p=0.00047) were associated with inferior OS. In multivariate analysis, age (HR 1.03, p=0.0026) and patients currently on treatment (HR 1.82, p=0.04) had inferior OS. There was a trend towards inferior outcomes in patients receiving monoclonal antibodies in univariate analysis (HR 1.82, p=0.081) but not in multivariable analysis (HR=1.29, p=0.48). Use of steroids was not statistically related to mortality (HR 1.79, p=0.074). Finally, contrary to other cohorts, no improvement in OS was observed in patients diagnosed later on the pandemic (fig. 2). Conclusion: In this large cohort of Latin American patients with lymphoma malignancies, our updated analysis showed a maintained dismal prognosis with COVID-19 infection. With a median follow up of 37 days, the 100-day OS was 64%. Older age and ongoing active cancer treatment were significantly associated with mortality. The use of monoclonal antibodies and systemic corticosteroids were not statistically associated to poor survival. Current efforts are focused on improving immunization in the Latin American population. There is an unmet need for improving survival in patients with hematologic malignancies and COVID-19 infection. Figure 1 Figure 1. Disclosures Perini: Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau. Otero: ASTRA ZENECA: Current Employment. Abello: Dr Reddy's: Research Funding; Amgen: Honoraria; Janssen: Honoraria. Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.
    Type of Medium: Online Resource
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 7
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 35-36
    Abstract: Introduction: SARS-COV-2 pandemic has infected approximately 20 million people worldwide and more than 700.000 fatalities have been reported. Patients with malignant hematological diseases are at particular risk for unfavorable outcomes, including intensive care unit (ICU) admission, need for mechanical ventilation (MV) and death. There is paucity of data of the outcome of cancer patients with COVID-19 in low- and middle-income countries. GELL is a collaborative network of hematological centers in 13 countries in Latin America. In this retrospective study, we aimed to look at the outcome of lymphoma patients diagnosed with COVID-19 in Latin America. Methods: This is a retrospective study including patients with a diagnosis of lymphoma and COVID-19 infection. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma were excluded from the analysis. COVID-19 diagnosis was done by RT-PCR in all but 3 patients, in whom the diagnosis was done by serology. Active disease was defined as patients with detected disease in any setting (prior to therapy, relapse) or patients currently on treatment. Survival curves were plotted using Kaplan Meier method. Results: A total of 117 patients were available for analysis. Median age was 60 years old, and 44% of patients had at least one comorbidity, including 32% with hypertension, 17% with obesity, 11% with cardiovascular disease and 17% with diabetes. Most patients had aggressive lymphomas (67%), including 46% of patients with diffuse large B-Cell lymphoma (DLBCL). Follicular lymphomas was observed in 13% of patients and Hodgkin's lymphoma in 10% of patients. 84% of patients had active disease, and 70% of patients were currently on treatment. With a median follow up of 17 days from COVID-19 diagnosis, 78% were admitted to Hospital, 30% needed ICU support, and 27% needed MV. Importantly, 26% of patients died, most of them within 20 days from diagnosis (Fig. 1). There was no relation between active disease (p=0.23), current treatment (p=0.65) or use of monoclonal antibodies (p=0.24) with death. COVID-19 treatment data was available in 107 patients, and 72 of them received any treatment, being steroids, the most common treatment used (n=59). Conclusion: We confirm the dismal prognosis of patients with hematological malignancies and COVID-19 infection. In our cohort of Latin America patients with lymphoma and COVID-19, 26% of patients died with a median follow up of 17 days. No impact of current treatment or use of monoclonal antibodies were observed. 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; Abbvie: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Abello:Novartis: Consultancy, Honoraria; Amgen: Consultancy, Research Funding; Takeda: Honoraria, Research Funding; Dr. Reddy's: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding. Rojas:Novartis: Consultancy; Abbvie: Honoraria; Sandoz: Honoraria; Roche: Honoraria. Castillo:Beigene: Consultancy, Research Funding; Abbvie: Research Funding; Pharmacyclics: Consultancy, Research Funding; TG Therapeutics: Research Funding; Kymera: Consultancy; Janssen: Consultancy, Research Funding. Villela:amgen: Speakers Bureau; Roche: Other: advisory board, Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
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  • 8
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4515-4515
    Abstract: Introduction: The neutrophil-lymphocyte ratio (NLR) is a measure of systemic inflammation that appears prognostic in different cancers. Although the exact mechanism remains to be elucidated, reduced lymphocyte intra tumor infiltration coupled with the formation of neutrophil extracellular traps (or NETosis) have been postulated as endogenous mechanisms for tissue damage and inflammation. Along this line, serum albumin has also been studied as a biomarker of inflammation and has been associated to prognosis in certain cancers. We have previously reported on the prognostic value of the NLR and serum albumin in diffuse large B-cell lymphoma (Villela, ASH meeting, 2019; Castro, ASH meeting, 2019) and peripheral T-cell lymphoma, not otherwise specified (Idrobo, ASH meeting, 2019), but nothing on follicular lymphoma (FL) yet. Therefore, we aim to investigate the role of different biomarkers on the prognosis of patients with FL diagnosed and managed in Latin America. Methods: We analyzed patients with FL diagnosed between 2010 and 2020 from 30 centers in 10 Latin American countries. The study outcomes were overall survival (OS) and progression-free survival (PFS) in relation to different biomarkers. Kaplan-Meier and log-rank test were used for survival analysis. Univariate and multivariate Cox regression analysis were used to estimate hazard ratios (HR) with a 95% confidence interval (CI) and adjusted to the Follicular Lymphoma International Prognostic Index (FLIPI) score. Outcomes with a p-value & lt;0.05 were considered statistically significant. Results: We identified 939 FL patients; 741 were included for the final analysis (median age 58 y, female 52%). There was no significant correlation between the NLR and other clinical factors such as: age, clinical stage, histological FL grading, and chemotherapy regimen used. A cutoff of 2.15 for NLR was defined as the maximum point for sensitivity and specificity based on ROC analysis. Table 1 and 2 summarizes the results from the univariate and multivariate analysis for 2 years OS and PFS, respectively. Both, serum albumin & lt;3.5 g/dL and a NLR & gt;2.15 were independently associated with worse OS (adjusted, aHR 2.48 [1.26-4.91], p=0.009; and 2.55 [1.21-5.37] , p=0.014) and PFS (aHR 1.62 [1.03-2.55], p=0.038; 2.22 [1.45-3.40] , p & lt;0.001), respectively. The lymphocyte:monocyte ratio (LMR) was not found to be prognostic for OS or PFS, although with a trend for worse PFS with a LMR ≤2.5. With a median follow of 43 months, (95% CI: 40-47), the survival rates in patients with FL and albumin & lt;3.5 were OS of 83% (vs. 95%) and PFS of 70% (vs. 83%); whereas in patients with NLR & gt;2.15 the survival rates were OS of 91% (vs. 96%) and PFS of 75% (vs. 88%) (Figures 1 and 2; table 3). Conclusions: In this study, serum albumin and NLR emerge as reliable predictors for survival for FL patients in Latin America. Although these markers have been associated to an increased inflammatory state in cancer patients; other factors such as poor nutritional status, and advanced disease stage due to delayed access to specialized cancer care in our region may have contributed to the observed outcome. Further studies are needed to better understand the role of these biomarkers on lymphoma care and to validate our findings. Lastly, we are currently working on evaluating these biomarkers on existing prognostic models and to improve prognostication for FL patients in Latin America. Figure 1 Figure 1. Disclosures Otero: ASTRA ZENECA: Current Employment. Ramirez-Ibarguen: Asofarma: Consultancy; MSD: Consultancy; Abbvie: Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Perini: Roche: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau; Takeda: Speakers Bureau; Abbvie: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau. Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2516-2516
    Abstract: Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma subtype. Early stage (I/II) disease is seen in up to 30% of all DLBCL cases, and although outcomes in this subgroup have been reported as optimal, relapses can still occur. Prognostic models such as the International Prognostic Index (Miller, NEJM, 1998) continues to be utilized for risk stratification in DLBCL. However, despite its limitations and lack of validation in specific demographic groups such as Latin American patients, no prognostic models exist for the evaluation of limited stage DLBCL. Therefore, we aim to investigate different clinico-epidemiological and laboratory variables and its impact on survival in early stage DLBCL. Methods: We conducted a retrospective study of newly diagnosed patients with early stage DLBCL. Using the Grupo de Estudio Latinoamericano de Linfroproliferativos (GELL) database, we selected patients that had early stage disease, defined as non-bulky stage I or II. The variables analyzed included demographic and clinical variables (e.g., age, ECOG performance status), the International Prognostic Index (IPI), and laboratory variables such as serum albumin, serum lactate dehydrogenase (LDH), serum beta-2-microglobulin, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio (LNR), and the platelet-lymphocyte ratio (PLR). To determine the variables associated with mortality, univariate and multivariate Cox regression (step-wise type) analysis was performed. Kaplan-Meier and log-rank test were used for survival analysis. Outcomes with a p-value & lt;0.05 were considered statistically significant. Results: We identified 1,375 patients with DLBCL; 503 were identified as early stage DLBCL of whom 498 had sufficient data for analysis. Almost all cases (n=483, 96%) had nodal disease as the primary site, and 15 (4%) extranodal, all within the gastrointestinal tract. There was a slight female predominance (51.8%). The median age at diagnosis was 64 (IQR: 50 -73) with 57.4% older than & gt;65 years. ECOG performance status of & lt;2 was seen in 77.2% of cases; elevated serum LDH in 32.4%; and elevated serum beta-2-microglobulin in 5.6% (n=11/192). Based on previous data, we evaluated and calculated variables that have been suggested as independent negative prognostic factors for overall survival; the proportion of patients with serum albumin & lt;3.5 mg/dL; LMR & lt;2, NLR & gt;4, and PLR & gt;376 was 34.4%, 10.3%, 9.2%, and 4.7% respectively. With a median follow-up of 45 months, the median 5-year overall survival (OS) rate was 72%. The therapy approaches used, response rates and outcomes with these approaches will be presented at the meeting. Results of the univariate and multivariate analysis are summarized in Table 1. We found that age over 65, ECOG performance status, serum albumin level, beta-2-microglobulin level, LDH ratio, LMR, NLR, PLR, and BCL-2 positivity by immunohistochemistry (IHC) were prognostic factors for OS in the univariate analysis. However, in the multivariate analysis, only NLR, serum albumin level and ECOG performance status were independent factor for worse prognosis. Survival rates were significantly shorter in patients with serum albumin & lt;3.5 g/dL (5-year OS of 49% versus 79%, respectively; p & lt;0.0001); NLR & gt;4 (5-year OS of 46% versus 73%, respectively: p=0.0013); and ECOG performance status ≥2 (5-year OS of 51% versus 74%, respectively; p & lt;0.0001) (Figures 1 to 3). Conclusion: In this large cohort of Latin American patients with early stage DLBCL most patients were older than 65, had nodal disease as the primary site, good performance status, with only a third of patients exhibiting elevated LDH. Moreover, we found serum albumin & lt;3.5 g/dL, NLR & gt;4 and ECOG ≥2 as negative prognostic factors for poor survival in early stage DLBCL. We are currently validating our findings in a prospective cohort of Latin American DLBCL patients and to improve clinical decision-making in those deemed at high-risk for early mortality. Figure 1 Figure 1. Disclosures Otero: Astra Zeneca: Current Employment. Oliver: Roche: Other: conference support and fees ; Abbvie: Other: conference support and fees . Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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