Biological and Classical Prognostic Factors with Impact on Overall Survival in Patients with Early Stage (I/II) Diffuse Large B-Cell Lymphoma: A Study from the Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL)

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 <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 >65 years. ECOG performance status of <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 <3.5 mg/dL; LMR <2, NLR >4, and PLR >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 <3.5 g/dL (5-year OS of 49% versus 79%, respectively; p<0.0001); NLR >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<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 <3.5 g/dL, NLR >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.

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Serum Albumin Is an Independent Factor Predicting Survival in Patients with Peripheral T Cell Lymphoma: A Multi-Institutional Study from the Latin American Working Group for Lymphomas (GELL)

Blood ◽

10.1182/blood-2019-123588 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4047-4047

Author(s):

Henry Idrobo ◽

Brady E. Beltrán ◽

Luis Villela M ◽

Marialejandra Torres Viera ◽

Victoria Otero ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Serum Albumin ◽

Board Of Directors ◽

Latin American ◽

Research Funding ◽

Prognostic Index ◽

Advisory Committees ◽

Cox Proportional Hazard ◽

Cox Proportional Hazard Regression

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.

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Predicting Time to Initial Treatment in Early Stage CLL - Integration of Classical and Novel Prognostic Factors.

Blood ◽

10.1182/blood.v112.11.2093.2093 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2093-2093

Author(s):

Michael J. Keating ◽

Susan Lerner ◽

Xuemei Wang ◽

Laura Z. Rassenti ◽

Susan O’Brien ◽

...

Keyword(s):

Prognostic Factors ◽

Lymph Node ◽

Initial Treatment ◽

Early Stage ◽

Tumor Burden ◽

Fish Cytogenetics ◽

Watch And Wait ◽

Mutation Status ◽

Beta 2 ◽

Beta 2 Microglobulin

Abstract CLL patients (pts) who are not eligible for initiation of treatment by the NCI Working Group criteria (1996) are traditionally monitored on a “watch and wait” approach. There is increasing interest in initiating therapy earlier in pts who are considered high risk. The most important advice pts require in the “watch and wait” category is whether they will need treatment and when. There are a number of traditional prognostic factors that potentially identify those “watch and wait” (W&W) pts most likely to need treatment. These have recently been amplified by the discovery of new prognostic factors such as the immunoglobulin (IgVH) mutation status, FISH cytogenetics, ZAP-70, and CD38 expression on CLL cells. Most reports have emphasized the new prognostic factors without consideration of traditional characteristics such as tumor burden, stage, etc. Since January 2004 FISH, IgVH mutation status, ZAP-70, and CD38 were characterized for most pts presenting to M. D. Anderson Cancer Center. We identified an early stage low tumor burden group of 826 pts (W&W) defined with as having lymph nodes < 3 cm in the longest dimension, splenomegaly < 5 cm, and Rai stage 0 – II. Twenty-four percent of these pts have received treatment in the first two years of follow-up. From the traditional prognostic factors, number of lymph node sites (cervical, axillary, and inguinal), absolute lymphocyte count (ALC), serum beta-2-microglobulin (B2M) levels were highly correlated with time-to-initial treatment (P<.001). The predictive power of these characteristics was also confirmed in an earlier historic patient population. When these three characteristics are evaluated in multivariate analysis, IgVH mutation status, ZAP-70, and FISH cytogenetics all add independent prognostic power. When these three novel characteristics were evaluated in multivariate model with the traditional characteristics, the most important were the number of node sites, ALC, B2M, FISH, IgVH mutation status, and then ZAP-70. Clinical only +Mutation Status +ZAP 70 +FISH + All 3 No. Lymph Node Sites 1 1 1 1 1 ALC 2 2 2 2 2 Beta-2-microglobulin 3 4 4 4 4 Mutation Status -- 3 -- -- 5 ZAP-70 -- -- 3 -- 6 FISH -- -- -- 3 3 Integration of novel prognostic factors into readily clinically available characteristics will enable us to develop a nomogram for predicting probability of each patient requiring therapy at one year, two years, and eventually five years. This nomogram will be presented when completed and then will be available for validation in independent patient populations studied by other groups.

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BIK (Bcl2-Interacting Killer) CpG Methylation Status in Multiple Myeloma Patients: a Potential Predictor of Relapsed/Refractory Disease.

Blood ◽

10.1182/blood.v114.22.2397.2397 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2397-2397

Author(s):

Eleftheria Hatzimichael ◽

Aggeliki Dasoula ◽

George Dranitsaris ◽

Amalia Vassou ◽

Justin Stebbing ◽

...

Keyword(s):

Multiple Myeloma ◽

Cpg Island ◽

Performance Status ◽

Methylation Status ◽

Cpg Methylation ◽

Epigenetic Silencing ◽

Refractory Disease ◽

Ecog Performance Status ◽

Beta 2 ◽

Beta 2 Microglobulin

Abstract Abstract 2397 Poster Board II-374 Background-Aim: BIK (bcl2-interacting killer) is the founding member of the BH3-only family proapoptotic proteins and is implicated in the selection of B cells in humans. The expression of BIK in cancer is prevented by chromosomal deletions or by epigenetic silencing. On the other hand, BIK upregulation is induced by proteasome inhibitors such as bortezomib and MG132. Although it has been shown that BIK is a target of epigenetic silencing in the IL-6 dependent multiple myeloma cell line KAS-6/1, no studies exist regarding the CpG methylation status of BIK in primary tumors. We wished to examine the CpG methylation status of BIK in patients with multiple myeloma (MM). Patients and methods: Bone marrow aspirate samples from individuals with MM were obtained at diagnosis. Methylation-specific PCR (MSP) was employed to study methylation in the BIK CpG island. Genomic DNA was isolated and bisulphite modification performed using commercially available kits (QIAmp DNA mini kit, Qiagen and EZ DNA methylation kit, ZymoResearch respectively). Control methylated (CpG GenomeTM Universal Methylated, Chemicon International) and unmethylated genomic DNAs were included in each experiment. Ten bone marrow samples from individuals with borderline thrombocytopenia, that proved to have no haematological malignancy, served as negative controls. Logistic regression analyses were used to measure the association between gene methylation and age, ISS stage, ECOG performance status, extramedullary disease, bone disease, anemia (Hb 10 mg/dl), serum albumin and beta 2 microglobulin levels and relapsed/refractory disease. Results: Methylation in the BIK CpG island was studied in 40 MM patients (21 male, 19 female, mean age 66). ISS staging were as follows: stage I 14 patients (36%), II 12 patients (31%), III 12 patients (31%). Methylation of the BIK CpG island was founded in 16 patients (40%) and men were more likely to be methylated (OR=3.08, p=0.098). No correlation was found between BIK CpG methylation and age, ECOG performance status, ISS staging, anemia, beta 2 microglobulin levels, albumin levels, and overall survival. Patients methylated for BIK had a 2-fold tendency to have bone disease (p=0.35) and a 3-fold tendency to have extramedullary disease (p=0.14). Notable, patients with methylated BIK had a higher risk of relapsed/refractory disease (OR=5.4, p=0.033). Conclusions: To the best of our knowledge, this is the first demonstration of aberrant methylation in the BIK CpG island in MM patients. Interesting associations between BIK CpG methylation and some relevant clinical parameters in patients with MM were suggested by the data. Most importantly, BIK CpG methylation in this series of patients was found to be strongly associated with relapsed/refractory disease. These findings warrant further evaluation in a larger sample of patients in order to better define the prognostic and clinical utility of BIK methylation in MM. Patients with refractory/relapsed disease could possibly benefit from agents enhancing BIK expression. Disclosures: No relevant conflicts of interest to declare.

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Primary Non-Hodgkin’s Lymphoma of Stomach: To Report 54 Patients and Analysis of Major Reported Series

Lymphoma ◽

10.1155/2013/583826 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9

Author(s):

Mansour Ansari ◽

Hamid Nasrolahi ◽

Amir Abbas Kani ◽

Seyed Hasan Hamedi ◽

Samira Razzaghi ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Early Stage ◽

Performance Status ◽

Univariate Analysis ◽

International Prognostic Index ◽

Gastric Lymphoma ◽

Prognostic Index ◽

Disease Free Survival ◽

B Cell Lymphoma

Introduction. This study aimed to report the characteristics, prognostic factors, and treatment outcomes of 54 patients with primary gastric lymphoma. Materials and Methods. This retrospective study was carried out by reviewing the medical records of 54 adult patients diagnosed at a tertiary academic hospital. All the patients were treated with curative intent. Forty-four patients (81.5%) underwent gastrectomy followed by adjuvant chemotherapy and/or radiotherapy, whereas 10 ones (18.5%) were treated with chemotherapy alone or with radiotherapy. Results. The study was conducted on 25 males and 29 females with the median age of 50 years. Diffuse large B-cell lymphoma (DLCL) (67%) and Mucosa Associated Lymphoid Tissue (MALT) lymphoma (26%) were the most common histologic types. Besides, 36 (59%), 16 (30%), 5 (9%), and 1 (2%) patients were in stages I, II, III, and IV, respectively. The 5-year disease-free survival and overall survival were 64.7% and 67%, respectively. In univariate analysis for overall survival, International Prognostic Index (IPI) (), the WHO performance status (), Ann Arbor stage (), age (), and LDH serum level () were the prognostic factors. Conclusion. Gastric lymphoma tends to present in early stage of the disease and has a favorable outcome.

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Assessment of Different Biological Variables (Serum Albumin, β-2-Microglobulin, Lymphocyte/Monocyte ratio, Neutrophil/Lymphocyte ratio, Platelet/Lymphocyte ratio) in a Retrospective Cohort of 525 Diffuse Large B-Cell Lymphomas As Predictor Factor(s) for Overall Survival

Blood ◽

10.1182/blood-2019-123841 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1613-1613

Author(s):

Luis Villela M ◽

Ana Ramirez-Ibarguen ◽

Brady E. Beltrán ◽

Victoria Otero ◽

Denisse A. Castro ◽

...

Keyword(s):

Overall Survival ◽

Serum Albumin ◽

B Cell ◽

Latin American ◽

Research Funding ◽

Cox Regression ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Biological Variables ◽

Large B Cell

Introduction. Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas (NHL). The use of chemoimmunotherapy (R-CHOP) in DLBCL has improved Overall Survival (OS). However, there are among 45-55% of patients who will die due to relapse, progression (refractoriness) or toxicity to treatment. Genomic classifications are difficult to use in clinical practice, especially in lain America, due to the need of trained personnel and cost. So, we continue using the International Prognostic Index (IPI) and its variations (e.g. revised-IPI, NCCN-IPI) for prognostic purposes. However, other biological variables have been reported to be prognostic, such as serum beta-2-microglobulin (B2M), lymphocyte/monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR), platelets/lymphocyte ratio (PLR) and serum albumin (SA). These factors have been associated with burden of disease, inflammation and nutritional status. Aim. Therefore, we performed a retrospective analysis of the databases of two Latin American groups to determine which biological variable is the most powerful factor prognostic of OS. Methods. A total of 1,250 patients were analyzed from two databases [(Grupo de Estudio para el Linfoma Mexicano (GELMEX) and the Grupo de Estudio para el Linfoma Latino Americano (GELL)], where 525 patients met the following inclusion criteria: DLBCL diagnosis by immunochemistry; complete data on absolute lymphocyte, absolute monocyte, absolute neutrophil and absolute platelet count, serum B2M and SA; and complete data on traditional variables for calculating risk groups for IPI, NCCN-IPI & R-IPI. The LMR, NLR and PLR was obtained. We evaluated the AUC of the biological variables and the differences among each one of them (including cut-off). Kaplan-Meier curves (KMC) were estimated and subsequently, the inference of OS was evaluated by Hazard Ratio (HR) Cox-regression in univariate/multivariate analyses by forward model. All variables with p<0.05 were considered independent variable for the multivariate analysis. Outcomes: Clinical characteristics of the cohort (n=525) were as follows: median follow-up time was 32 months (range: 0.2-132), 52% were male, 60% had more than 60 y/o (≥75 y/o, 21%), one third (32%) had a bad performance status (ECOG ≥2), 63% had advanced stage (III-IV), 49% had high serum lactate dehydrogenase (LDH; ratio 1.1-2.9, 41%; ratio ≥3, 8%), 21% had ≥2 extranodal sites involved (28%, NCCN-specific sites) and 43% had bulky disease. SA had the best AUC comparing with other variables (see figure 1). 5-y OS rates by SA (>3.2 mg/dL vs. ≤3.2 mg/dL) were 72% vs 34% (Log Rank p<0.0001), by B2M (<4 µg/dl vs. ≥4 µg/dL) were 68% vs. 45% (p<0.0001), by LMR (≥2.2 vs. <2.2) were 67% vs. 47% (p<0.0001), by NLR (<4 vs. ≥4) were 70% vs. 52% (p<0.0001) and by PLR (<475 vs. ≥475) were 65% vs. 44% (p<0.0001). In the univariate Cox regression analysis, SA ≤3.2 mg/dL was associated with HR 3.41 (CI95% 2.47-4.64), B2M ≥4 µg/dL with HR 2.13 (CI95% 1.57-2.88), LMR <2.2 with HR 2.11 (CI95% 1.56-2.87), NLR ≥4 with HR 1.92 (CI95% 1.45-2.55), and PLR ≥475 with HR 2.17 (CI95% 1.52-3.1)]. The multivariate Cox regression analyses (Forward model) showed that SA ≤3.2 mg/dL, B2M ≥4 µg/dL and high NLR ≥4 retained their prognostic value for worse OS (HR 2.87, CI95% 2.1-3.90; p=<0.0001; HR 1.40, CI95 1.02-1.94; p=0.036; and HR 1.43, CI95% 1.06-1.92; p=0.01, respectively). SA ≤3.2 mg/dL was the only independent factor associated with worse OS when adjusted by IPI (HR 2.53, CI95% 1.75-3.67; p<0.0001), NCCN-IPI (HR 2.51, CI95%1.81-3.5; p<0.0001) and R-IPI (HR 3.12, CI95%2.34-4.16; p<0.0001). Conclusion: Low SA emerges as an easy-to-use, important biological factor prognostic of worse survival, independent of the IPI, R-IPI and NCCN-IPI scores, in Latin American patients with DLBCL treated with chemoimmunotherapy. Figure 1 Disclosures M: Roche-Mexico: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Merck-Sharp-Dome: Speakers Bureau. Ramirez-Ibarguen: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. Gomez-Almaguer:Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Abello:Takeda: Other: Participation in advisory board meeting. Tena:Roche-Mexico: Employment. Castillo:Abbvie: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; TG Therapeutics: Research Funding.

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An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease

Cancer ◽

10.1002/cncr.10998 ◽

2002 ◽

Vol 95 (12) ◽

pp. 2534-2538 ◽

Cited By ~ 24

Author(s):

Gregory M. Chronowski ◽

Richard B. Wilder ◽

Susan L. Tucker ◽

Chul S. Ha ◽

Andreas H. Sarris ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

Early Stage ◽

Elevated Serum ◽

Hodgkin Disease ◽

Adverse Prognostic Factor ◽

Beta 2 ◽

Beta 2 Microglobulin

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A Phase II Study of the Efficacy and Safety of an Intensified Schedule of Azacitidine (AZA) in Intermediate-2 and High Risk MDS Patients: A Study By the Groupe Francophone Des Myelodysplasies (GFM)

Blood ◽

10.1182/blood.v126.23.2869.2869 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2869-2869

Author(s):

Lionel Ades ◽

Agnes Guerci-Bresler ◽

Pascale Cony-Makhoul ◽

Laurence Legros ◽

Marie Sebert ◽

...

Keyword(s):

Overall Survival ◽

Stable Disease ◽

Research Funding ◽

Response Rate ◽

Performance Status ◽

Survival Rates ◽

Ecog Performance Status ◽

Major Mechanism ◽

Grade 3 ◽

Number Of Treatment

Abstract Background: Although azacitidine (AZA) improves survival over conventional treatments in higher risk MDS (Lancet Oncol, 2009), median overall survival (OS) with AZA is only about 2 years, the CR+PR rate about 30%, and further improvements are needed. Gene hypomethylation appears to be a major mechanism of action of AZA but, with the typical 7 days of administration every 28 days, reversal of gene hypomethylation is seen at the end of each cycle (Braiteh F, Clin Cancer Res 2008), suggesting that increasing the number of treatment days could improve AZA results. This trial tested the hypothesis that an AZA regimen with more days of drug administration (ie using the standard daily dose of 75 mg/m2, but during 5 days every 14 days) could increase the response rate, and that this improvement could translate into better OS. Methods: Patients (pts) aged 18-75 years with ECOG performance status (PS) of 0-2 and no major comorbidities preventing administration of an intensified regimen of AZA, with IPSS int-2 or high MDS, CMML with WBC < 13,000/mm3 and marrow blasts > 10% , or AML with 20-30% marrow blasts (ie EU label for AZA) who had received no prior treatment for their MDS/AML except ESAs could be included. Treatment consisted of AZA 75mg/m2/d for 5 days every 14 days for 4 cycles (AZA-14, cycles 1-4). Patients achieving CR or PR then received 4 cycles of AZA 75mg/m2/d during 5 days every 21 days (AZA-21, cycles 5 to 8) followed by classical cycles of AZA 75mg/m2/d for 7 days every 28 days, to be continued until progression/relapse or toxicity arose. This schedule corresponded to a 30% increase in the number of days of AZA during the first 3 months of treatment. Patients not obtaining CR or PR after the initial 4 cycles of AZA-14 received 4 additional cycles of AZA 14 (cycles 5 to 8). Patients not obtaining CR, PR or HI after 8 cycles of AZA-14 were excluded from the trial. The primary endpoint was response after 4 and 8 cycles (IWG 2006 criteria). Median [IQR] are reported unless specified. Results: 27 patients were included, of whom 1 was excluded for consent withdrawal. 26 patients (M/F: 19/7, median age 66) enrolled between 2011 and 2013, were thus analyzed, including 1 ARSI, 2 RCMD, 3 RAEB1, 13 RAEB2, 2 CMML and 5 AML (with 20 to 30% marrow blasts). Karyotype (IPSS) was favorable in 11 pts, intermediate in 6 patients and unfavorable in 9 pts. Median marrow blast was 13.5% (IQR 9.7-18.0), baseline platelet count was 72.5 G/l (43.5-177.0) including 69% with platelet<50 G/L, baseline Hb level was 9.8 g/dl (8.9-10.6), and baseline ANC was 1.2 G/l (0.6-2.3). IPSS was int-1 in 1, int-2 in 16 patients and high in 9 patients. With a median follow-up of 20 months, 342 cycles were administered (median 12/patient, including 23 (88%) patients who received 6 or more cycles). Cycle 2 was performed at a median of 14 (14-14) days after cycle 1 and had to be delayed beyond d15 in only 1 patient. Cycles 3 and 4, scheduled at d28 and d42, were slightly delayed in many pts (and were administered at a median of d35 and d51 from AZA onset). 1 pt terminated the study before cycle 4. Regarding toxicity, 25 SAEs (grade 3-4) were reported in 16 patients, including 21 infectious events, 1 being lethal. After 4 cycles, 1 achieved CR, 6 PR, 7 marrow CR, 5 stable disease with HI (overall response rate 19/26=73.1%). Overall, after 8 cycles, the ORR was 22/26 (85%), including 4 CR, 6 PR, 11 mCR and 1 stable disease with HI. Median survival was 21 months, while one and 2-year overall survival rates were 73%[95CI: 58%;92%] and 41%[95CI: 25%;66%], respectively. No prognostic factors for OS, including IPSS (p=0.63), bone marrow blast % (p=0.24), sex (p=0.42), IPSS cytogenetic group (p=0.30) and PS (p=0.64) was found. Conclusion: In this population of relatively "fit" Higher risk MDS, an intensified schedule of AZA seems feasible without obvious increase in toxicity compared to the classical 7 day schedule of azacitidine. Cycles were delayed in a limited proportion of patients and no extra toxicities were observed. Both the ORR of 85% and the 73% overall survival at 1 year are encouraging. Disclosures Guerci-Bresler: ARIAD: Speakers Bureau; BMS: Speakers Bureau; Novartis: Speakers Bureau; PFIZER: Speakers Bureau. Legros:ARIAD: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; BMS: Speakers Bureau. Fenaux:Novartis: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

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Timeliness of adjuvant chemotherapy in patients with resected pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18038 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18038-e18038

Author(s):

David Deng ◽

Winson Y. Cheung

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Adjuvant Chemotherapy ◽

Proportional Hazards ◽

Performance Status ◽

Population Based ◽

Cox Proportional Hazards ◽

Study Cohort ◽

Ecog Performance Status

e18038 Background: Timeliness of adjuvant chemotherapy is an important predictor of survival for patients with breast and colorectal cancer whereby long delays has been shown to detrimentally impact outcomes. The effects of adjuvant treatment timing remain largely unknown for early pancreatic cancer. This study aims to identify independent predictors of treatment timeliness and overall survival in this patient population. Methods: We conducted a retrospective, population-based analysis of 179 patients with resected pancreatic cancer who subsequently started adjuvant chemotherapy between 2008 and 2014 at any 1 of 6 cancer centers across British Columbia, Canada. Logistic regression was used to identify predictive factors for adjuvant chemotherapy timing. Prognostic factors for survival were ascertained using multivariate Cox proportional hazards models. Results: Our study cohort included 91 men (51%) and 88 women (49%). At time of diagnosis, 145 patients (81%) had nodal involvement and 107 patients (60%) had good ECOG performance status (ECOG 0-1). The median age of diagnosis was 67 (range 37-85) years. The median interval between surgery and start of adjuvant chemotherapy was 70 (range 19-46) days. Abnormal bilirubin was the only factor significantly correlated with delayed chemotherapy (OR, 3.89; 95% CI, 1.55-9.73; P = 0.004). Median overall survival was 468 days following resection (95% CI, 425-538). Multivariate survival analysis showed that high CA 19-9 levels (HR, 2.44, 95% CI: 1.36-4.40, P = 0.003) and abnormal bilirubin (HR, 0.40; 95% CI, 0.22-0.73; P = 0.003) were prognostic factors for overall survival. Median survival for patients who waited up to 35, 70 or 105 days for chemotherapy following resection were 588 days (95% CI, 270-776), 490 days (95% CI, 360-688) and 466 days (95% CI, 432-538) respectively. Overall, timeliness was not predictive of survival (HR, 1.12; 95% CI, 0.64-1.97; P= 0.70). Conclusions: Patients with hyperbilirubinema experienced delays in adjuvant chemotherapy, likely due to the need for relief of biliary obstruction and subsequent recovery. However, timeliness of adjuvant chemotherapy did not influence outcomes, suggesting that treatment should still be considered irrespective of timing.

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Revisiting the Impact of Immunoglobulin Isotypes in Multiple Myeloma

Blood ◽

10.1182/blood-2020-138903 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 19-19

Author(s):

Susan Bal ◽

Smith Giri ◽

Kelly N. Godby ◽

Luciano J. Costa

Keyword(s):

Multiple Myeloma ◽

Renal Function ◽

Prognostic Factors ◽

Renal Dysfunction ◽

Research Funding ◽

Performance Status ◽

Prognostic Impact ◽

Ecog Performance Status ◽

Immunoglobulin Isotypes ◽

Race Ethnicity

Background Multiple Myeloma (MM) is a malignancy of terminally differentiated B lymphocytes (plasma cells, PCs) characterized by secretion of immunoglobulins and/or light chains (LCs). Association of immunoglobulin isotypes with survival in the context of contemporary therapies and accounting for modern prognostic factors has not been determined. Methods We utilized the Flatiron Health Electronic Health Record (EHR)-derived de-identified database to source patients (pts) with newly diagnosed MM from 01/2011 to 02/2020 with documented isotype data as part of the initial diagnostic work up. This nationwide database comprises de-identified, longitudinal patient-level demographic, clinical, and outcomes data curated via technology enabled abstraction. We used self-reported race and ethnicity and constructed a composite race/ethnicity variable as used by the National Cancer Institute. Similarly, we defined baseline labs (hemoglobin, serum creatinine, calcium, LDH) as those available within 90 days of diagnosis. We compared baseline characteristics using appropriate bivariate methods. Finally, we used Kaplan-Meier methods and Cox proportional hazard regression models to compare overall survival (OS), from the date of diagnosis, among the different isotypes (IgA, IgD, IgM, Light Chain (LC), others) with IgG MM after adjusting for known prognostic variables such as FISH abnormalities, ISS, renal function, age, sex, race/ethnicity, LDH, ECOG performance status, and treatment. Results We identified 8468 patients in the database who met the inclusion criteria. Patient with IgA MM (N=1688) were more likely to have ISS-III (IgA 21% vs. IgG 16%, p<0.001), anemia (IgA 41% vs. IgG 35%, p<0.001) and t(4;14) (IgA 8% vs. IgG 4%, p<0.001) than patients with IgG MM (N=4858). LC MM (N=1748) have more renal dysfunction (LC 21% vs. IgG 11%, p<0.001) and t(11;14) (LC 17% vs. IgG 8%, p<0.001). Patients with IgD MM (N=44) were younger, more likely to be male and non-Hispanic White, have ISS-III, high LDH, anemia and renal dysfunction and t(11;14). Patients with IgM MM (N=84) had higher incidence of hypercalcemia and lower proportion of patients with high LDH (Table). Across all groups 3106 (36.7%) patients received therapy containing a proteasome inhibitor (PI) and an immunomodulatory agent based triplet (IMiD), while 1458 (17.2%) received IMiD-based doublet, 2284 (27.0%) PI-based doublet, and 2109 (24.9%) received hematopoietic cell transplantation. Patients with IgA (mOS 4.7 vs 5.6 years, p<0.001) and LC MM (4.8 vs. IgG 5.6 years, p<0.001) patients have inferior OS (Figure). The adverse prognostic impact of IgA (HR 1.2, 95% CI 1.1-1.3, p<0.001) and LC isotypes (HR 1.2, 95% CI 1.1-1.3, p<0.001) on OS persisted even after adjustment for FISH abnormalities, ISS stage, renal function, age, sex, race/ethnicity, ECOG performance status, LDH, and treatment. Conclusion Using a contemporary "real world" dataset, we illustrate the distinct clinical features of MM with different immunoglobulin isotypes. Our findings suggest that IgA and LC MM are associated with poor survival suggestive of their unique biology beyond presence of high-risk FISH abnormalities and other adverse prognostic factors. Figure Disclosures Costa: Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; Genentech: Consultancy; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

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Retrospective analysis of glioblastoma multiforme (GBM) patients treated initially with BCNU compared to temozolomide (TMZ) with concomitant radiation therapy

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.2071 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 2071-2071

Author(s):

M. Vinjamuri ◽

R. Adumala ◽

R. Altaha ◽

J. Hobbs ◽

E. Crowell

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Retrospective Analysis ◽

Performance Status ◽

Progression Free Survival ◽

Standard Of Care ◽

Survival Curves ◽

Ecog Performance Status ◽

Free Survival ◽

Significant Difference

2071 Background: TMZ and radiation as initial treatment has become the standard of care for GBM. There are no randomized studies comparing TMZ to BCNU in GBM. Methods: We did a retrospective analysis of all 100 GBM patients (pts) diagnosed by our pathology department in the last 10 years. 20 pts were excluded, in 12 pts no chemotherapy was given and there was no data available for 8 pts. BCNU treatment was given in earlier years than TMZ generally. Overall survival (OS), progression free survival (PFS) and four prognostic factors were compared between BCNU and TMZ treated groups. Results: Results show that there is no significant difference in OS and PFS between the two groups. Survival curves were superimposable. This is despite the fact that tumor size and ECOG performance status were worse, though not significantly so in the BCNU group. Age was the only variable that correlated with survival. After correcting for age there was still no difference in PFS and OS between the BCNU and TMZ group. Conclusions: Our study fails to shows superiority of TMZ over BCNU despite the fact that the BCNU group had worse prognostic factors. A randomized comparison of these two agents seems justifiable. [Table: see text] No significant financial relationships to disclose.

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