Clinical and Quality of Life Predictors of Failure to Achieve Event Free Survival at 24 Months in Patients Aged 70 Years and Older with Diffuse Large B-Cell Lymphoma

Abstract Background Age has long been recognized as a poor prognostic factor in diffuse large B-cell lymphoma (DLBCL) and more recently, a lower baseline quality of life (QOL) in patients with aggressive lymphomas has been associated with an inferior overall survival (OS) (Thompson et al, 2018). Older patients with DLBCL are a heterogeneous population and commonly have comorbid conditions. A concerted effort to identify prognostic factors specific to this population is needed, including QOL. Event free survival at 24 months (EFS24) is a well validated endpoint in DLBCL (Maurer et al, 2014) and is clinically relevant in older patients. We hypothesized that baseline clinical factors and QOL would be associated with EFS24 this patient group. Methods Newly diagnosed lymphoma patients were prospectively enrolled within 9 months of diagnosis into the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER). Patients ≥70 years of age with DLBCL were utilized in this study. All pathology was reviewed by a lymphoma hematopathologist. Clinical variables were abstracted from the medical record. QOL was assessed at enrollment using a single item Linear Analogue Self-Assessment (LASA) and the 27-item Functional Assessment of Cancer Treatment-General questionnaire (FACT-G), which includes physical, social, emotional, and functional well-being domains. QOL scores were converted to a 0-100 scale to facilitate modeling. QOL was analyzed in patients who completed 80% of the FACT-G questions. Characteristics of the study population were compared using the Wilcoxon rank sum test. Odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate the associations of clinical and continuous QOL variables with failure to achieve EFS24 using logistic regression models, with a stepwise approach to identify parsimonious multivariate models. Results A total of 389 patients ≥70 years were identified with DLBCL in the MER from 2002-2015; patient characteristics are described in the Table. In the entire study population, univariate predictors of EFS24 failure included age (OR per 10 years=1.85, 95% CI: 1.26-2.71), ECOG PS ≥2 (OR=4.78, 95% CI: 2.92-7.83), elevated LDH (OR=3.59, 95% CI: 2.27-5.65), stage III-IV (OR=1.94, 1.25-3.02), bulky disease (OR=2.86, 95% CI: 1.43-5.72), international prognostic index (OR=8.71 for IPI 5 vs IPI 0, 95% CI: 3.04-24.9), and receipt of an anthracycline (OR=0.25, 95% CI: 0.12-0.51), while none of the other variables in the Table, including the QOL variables, were statistically significant. In a stepwise multivariate analysis, only ECOG PS ≥2 (OR= 3.56, 95% CI: 2.09-6.06) and elevated LDH (OR=2.86, 95% CI: 1.78-4.60) remained significant predictors of EFS24 failure. QOL data were available on 220 patients, with 120 completing QOL questionnaires prior to receipt of chemotherapy. Compared to participants who completed their FACT-G before the initiation of chemotherapy, the median FACT-G physical (85.7 v. 71.4, p=0.005) and functional (71.4 vs 57.1, p=0.008) scores were lower in participants completing FACT-G after initiation of therapy, were higher on FACT-G emotional (79.2 vs 83.3, p=0.03), and showed no differences on FACT-G social (89.3 vs 91.7, p=0.60) or FACT-G total score (78.2 vs 74.1, p=0.17). Given these differences, we restricted the QOL analysis to those with pre-treatment data. In univariate analysis, the LASA score (OR= 0.98, 95% CI: 0.84-1.14), the FACT-G total (OR=0.99, 95% CI: 0.96-1.01), physical (OR=0.98, 95% CI: 0.97-1.00), social (OR=1.00, 95% CI: 0.98-1.03), emotional (OR= 1.00, 95% CI: 0.98-1.02), and functional (OR=0.99, 95% CI: 0.98-1.01) scores were not associated with EFS24 failure. In a stepwise multivariate analysis of clinical variables in patients with pretreatment QOL scores, only ECOG PS ≥2 (OR=3.56, 95% CI: 1.30-9.72) and female sex (OR=0.37, 95% CI: 0.16-0.85) were associated with failure to achieve EFS24. Conclusions In patients aged 70 years and older, ECOG PS and LDH were the strongest independent predictors of failure to achieve EFS24. As expected, physical and functional scores were lower in patients who completed their QOL after initiation of treatment. Restricting the analysis to patients with pre-treatment data, QOL was not associated with failure to achieve EFS24. Additional studies are needed to identify the most robust clinical predictors of EFS24, while QOL does not appear to be an important predictor of EFS24. Disclosures Reagan: Seattle Genetics: Research Funding. Maurer:Morphosys: Research Funding; Celgene: Research Funding; Nanostring: Research Funding. Cerhan:Celgene: Research Funding; Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board.

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Primary Splenic Diffuse Large B-Cell Lymphoma (PS-DLBCL): Splenectomy Improves Survival

Blood ◽

10.1182/blood.v124.21.4439.4439 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4439-4439 ◽

Cited By ~ 1

Author(s):

Osnat Bairey ◽

Lev Shvidel ◽

Chava Perry ◽

Eldad J Dann ◽

Rosa Ruchlemer ◽

...

Keyword(s):

Overall Survival ◽

Performance Status ◽

B Cell Lymphoma ◽

Stage I ◽

Event Free Survival ◽

Ecog Performance Status ◽

Free Survival ◽

Large B Cell Lymphoma ◽

The Mean ◽

Ecog Ps

Abstract Introduction: Although the spleen is involved in about a third of patients with non-Hodgkin's lymphoma (NHL), primary splenic diffuse large B-cell lymphoma (PS-DLBCL) is rare having a reported incidence of less than 1% of all NHL. Most of the described series include small numbers of patients before the rituximab era and the role of splenectomy treatment in addition to immuno-chemotherapy is unknown. Methods: Data were retrospectively collected for 87 patients (pts) with PS-DLBCL treated in 7 medical centers in Israel during the years 1982-2013. Patients presenting with systemic disease with splenic involvement or those having a diagnostic biopsy from other nodal or extranodal disease were excluded. Results: The mean age was 59.6 years (range, 24-89 years); 57.5% were male. Abdominal pain was reported in 61 pts (81%), B symptoms in 49 pts (59%), ECOG performance status 0 - 1 in 85%. Stage I disease was recorded in 28%, II in 33%, III in 18%, and IV in 21%. Thrombocytopenia (<100,000/µl) was recorded in only 6 pts. Lactic dehydrogenase levels (LDH) were elevated in 69 pts (84%). Favorable International Prognostic Index (IPI) 0-2 was recorded in 62 pts (72%). The mean splenic length was 17.34±6 cm (range 7- 37 cm) and the mean splenic weight was 1216 gm±1243 gm (range 180-6000 gm). A splenic mass was found in 97% of pts, and its mean size was 9.26 cm (range 3-18 cm). The diagnostic procedure was core needle biopsy in 46 pts and splenectomy in 39 pts: 27 underwent open splenectomy and 12 laparoscopic splenectomy. Splenectomized pts had lower IPI (p<0.05) and lower stage (p<0.05) compared to non-splenectomized pts. Treatment: The CHOP regimen was given to 80 pts (92%), DA-EPOCH was given to 2 pts (2%) and 5 pts (6%) received other regimens. Rituximab was given to 68 pts (78%). Complete response was achieved in 67 pts (80%) and partial response in 8 (9%). Relapse occurred in 17 pts (22%). Survival: The median follow-up time was 7 years (range 0-19.4 years). During this period 24 pts died (27.5%). The 5-year overall survival (OS) was 76.6±4.9% and 5-year event-free survival (EFS) 67.2±5.5%. Splenectomy at diagnosis improved survival: the 5-year EFS was 85.4±6% and 54.7±8% for splenectomized and non-splenectomized pts respectively (p=0.02) and the 5-year OS was 91.2±5% and 67.9±7% respectively (p=0.08). For the 53 pts with stage I-II disease, both 5-year EFS and OS were better in the splenectomized pts (p<0.02, Fig 1). The 5-year EFS and OS in pts with stage I and II disease that were splenectomized at diagnosis was 89.6±6% and 96.4±3.5% as compared with 50.5±11% and 63.2±11% in pts who were not splenectomized (p=0.012 and 0.009). The EFS and OS were not influenced by the stage of the disease. Overall survival was associated with B symptoms (p=0.02), weight loss (p=0.04) and ECOG performance status (p=0.03). In a multivariate model, low ECOG PS and splenectomy independently predicted a better EFS (p=0.03 and 0.02 respectively), however for OS, low ECOG PS independently predicted better OS (p=0.03), while splenectomy had only marginal effect on the OS (p=0.056). Conclusions: In our group of pts, PS-DLBCL generally presented with abdominal pain, high LDH and a splenic mass. We demonstrate for the first time that splenectomy at diagnosis improves survival in early stages of PS-DLBCL. Our study is a retrospective one. Therefore, until prospective studies prove that early splenectomy in PS-DLBCL is beneficial in terms of overall survival, the risk and benefit of performing splenectomy should be weighed for each patient. Fig 1: (A) Event-free survival and (B) Overall survival in patients with primary splenic DLBCL and stages I - II disease who did or did not undergo splenectomy at diagnosis. Fig 1:. (A) Event-free survival and (B) Overall survival in patients with primary splenic DLBCL and stages I - II disease who did or did not undergo splenectomy at diagnosis. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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IPI24: An International Study To Create An IPI For The Event-Free Survival At 24 Months (EFS24) Endpoint For DLBCL In The Immunochemotherapy Era

Blood ◽

10.1182/blood.v122.21.362.362 ◽

2013 ◽

Vol 122 (21) ◽

pp. 362-362 ◽

Cited By ~ 2

Author(s):

Matthew J Maurer ◽

Herve Ghesquieres ◽

Jean-Philippe Jais ◽

Thomas E Witzig ◽

Corinne Haioun ◽

...

Keyword(s):

Bone Marrow Involvement ◽

B Cell Lymphoma ◽

Individual Risk ◽

Parameter Estimates ◽

Newly Diagnosed ◽

Event Free Survival ◽

Bulky Disease ◽

Free Survival ◽

Clinical Variables ◽

Ecog Ps

Abstract We have recently reported that event-free survival at 24 months from diagnosis (EFS24) is a robust endpoint for assessment of disease related outcome for newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-based immunochemotherapy (IC). Patients who achieve EFS24 following IC have a subsequent overall survival that is equivalent to the age and sex matched general population. The IPI was developed in the pre-rituximab era using OS/EFS endpoints. While the IPI is associated with outcome in the IC era, the original survival estimates for the IPI risk groups are outdated. The IPI is also a discrete risk classifier, with only 6 possible groups. Here we remodel the IPI using EFS24 as the endpoint in a large international cohort of patients treated with IC. This model provides an individual level 0-100% risk of failing to achieve EFS24 for each patient and can be used for patient prognosis, treatment stratification, and risk assessment. Methods Newly diagnosed DLBCL patients treated with immunochemotherapy from the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource, NCCTG N0489 clinical trial, GELA LNH2003B program, and a Lyon, France based hospital registry were included in the original EFS24 study. Patients with a relapse, progression, unplanned re-treatment, or death due to any cause within 730 days of diagnosis were considered a failure for the EFS24 endpoint. Patients alive and progression/relapse free at 730 days from diagnosis with no subsequent treatment following initial IC were considered a success for the EFS24 endpoint. Variables selected for potential model inclusion were the IPI components (age, stage, ECOG PS, number of extranodal sites, and LDH), as well as standard clinical variables typically reported in studies of DLBCL: presence of B-symptoms, bone marrow involvement, bulky disease (>10 cm), and sex. The IPI24, a prognostic model for EFS24, was developed using logistic regression models. Model building began by fitting the classic IPI score (0-5), then allowing individual IPI variables to carry different model weights and number of categories, followed by dropping insignificant variables, finally adding any additional significant variables. Model performance was assessed using bias corrected c-statistics, AIC, and R2 values. Model selection was done using the complete case set with multiple imputation on the full dataset used to refine parameter estimates for the final model. Results 1596 total patients were available for modeling. The median age was 62 (range 18-93) and 53% were male; 33% were IPI 0-1, 25% were IPI 2, 25% were IPI 3, and 17% were IPI of 4-5. The failure rate for achieving EFS24 was 29%. All variables but sex (p=0.33) were univariately associated with EFS24 (p<6.4x10-5). The original IPI had good prognostic ability for EFS24 (c=0.696, p=2.2x10-32). Allowing multiple categories for ECOG PS, stage, and age (continuous) improved model fit and prognostic ability (c=0.727). The number of extranodal sites was not significant when IPI variables were modeled separately and was removed from the model. Sex and bulky disease were additional significant variables when added to the model. Thus, the final IPI24 model contained the following risk predictors: male sex, ECOG PS (0 vs. 1 vs 2 vs 3-4), stage (I vs. II, vs. III vs. IV), LDH (elevated vs. normal range), bulky disease > 10cm, and age (continuous). This model resulted in improved fit and prognostic ability (c=0.749) over the standard IPI (c=0.696, bootstrap p<0.001). Model validation was performed on an additional 158 patients from the SPORE MER and showed good concordance (c=0.697). Additional validation is planned in a larger set of independent patients. Conclusion The IPI24, generated using standard clinical variables, yields an individual risk prediction for failing to achieve EFS24 following IC for treatment of DLBCL. The IPI24 has superior prognostic ability to the standard IPI and can be implemented in the clinic using a nomogram or as a simple electronic application. Disclosures: No relevant conflicts of interest to declare.

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Clinical Outcomes of R-CHOP Chemotherapy Alone Compared with R-CHOP Plus Radiotherapy in Patients with Localized, Non-Bulky Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood.v124.21.4421.4421 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4421-4421

Author(s):

Ji Hyun Park ◽

Dok Hyun Yoon ◽

Shin Kim ◽

Jung Sun Park ◽

Sang-wook Lee ◽

...

Keyword(s):

Overall Survival ◽

Clinical Outcomes ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Complete Response ◽

Event Free Survival ◽

Chop Chemotherapy ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Clinicopathologic Parameters

Abstract Introduction Although several previous studies addressed the role of radiation in treating localized diffuse large B-cell lymphoma (DLBCL), chemotherapy alone has shown promising efficacy with the emergence of Rituximab. Thus, we evaluated the clinical efficacy outcomes and failure patterns of patients with localized DLBCL according to two different treatment strategies, either 6 or more cycles of R-CHOP chemotherapy alone or 3 or 4 cycles of R-CHOP followed by involved field radiotherapy (IFRT). Methods A prospectively collected database from 21 tertiary centers participating the Consortium for Improving Survival of Lymphoma (CISL), built up for PROCESS study (NCT01202448) for secondary central nervous system involvement in DLBCL, was recruited for current study in addition to the Asan Medical Center (AMC) Lymphoma Registry. CISL database and AMC lymphoma registry consisted of data from patients with newly diagnosed DLBCL between August 2010 and August 2012, and between February 2004 and February 2012, respectively. Inclusion criteria were localized (stage I or II), non-bulky (<10cm in longest diameter) DLBCL treated with R-CHOP as 1st line chemotherapy, and patients either who received 6 or more cycles of R-CHOP chemotherapy only (R-CHOP alone group) or received 3 or 4 cycles of R-CHOP chemotherapy followed by IFRT (R-CHOP plus RT group). Comparisons of clinicopathologic parameters, clinical outcomes and the patterns of relapse were performed between two groups. The types of relapse were classified as either locoregional or distant, according to whether it involves any separate region from primary sites. Efficacy outcomes included complete response (CR) rate, 2-year overall survival (OS) rate, and 2-year event-free survival (EFS) rate. Results A total of 357 patients (CISL prospective cohort: 161 patients, AMC registry: 196 patients) were eligible for the analyses. Two hundred ninety nine patients (83.5%) received 6 or more cycles of R-CHOP chemotherapy alone, and 58 patients (16.2%) underwent 3 or 4 cycles of R-CHOP followed by IFRT. Median age was 54 years (range, 16-87). During the median follow-up of 24 months (range, 4-116 months), 35 patients (9.8%) experienced relapse, and 22 patients (6.1%) died. Two-year OS and EFS rate was 94.7% and 89.9%, respectively, and 345 out of 357 patients (96.6%) achieved CR. Comparing R-CHOP alone to R-CHOP plus RT group, there was no significant difference in clinicopathologic parameters. R-CHOP alone could achieve significantly higher CR rate of 97.7 % than 91.4% of R-CHOP plus RT group (p = 0.030). Two-year OS and EFS were significantly longer in R-CHOP alone group than R-CHOP plus RT group (96.1 vs 89.9 %, p = 0.029 and 91.7% vs 81.8%, p= 0.028) (Figure 1). Relapse rate was significantly lower in R-CHOP alone group compared with R-CHOP plus RT group than group (7.4% vs 22.4%, p=0.001), and distant relapses were also significantly lower (15.5% vs 2.7%, p<0.001). In addition, even only in relapsed patients, R-CHOP alone group showed lower incidence of distant relapses with marginal statistical significance (36.4% vs 69.2 %, p=0.062) (Table 1). Conclusion In our cohort, R-CHOP alone for six to eight cycles without IFRT could achieve significantly higher 2-year OS and EFS rate as well as CR compared with R-CHOP plus RT group. In addition, the rate of relapse and systemic failure were significantly lower in R-CHOP alone group, which altogether warrant further validation in prospective trial. Table 1. Explorative comparison of overall clinical outcomes and patterns of relapse between two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Total (%) R-CHOP alone group (%) R-CHOP plus RT group (%) P -value Number of patients 357 (100) 299 (83.5) 58 (16.2) Treatment response Complete response 345 (96.6) 292 (97.7) 53 (91.4) 0.030 Overall response 351 (98.3) 294 (98.3) 57 (98.3) 1.000 Rate of relapse 35 (9.8%) 14 (7.4) 11 (22.4) < 0.001 Median time to relapse (95% CI) 11 (7-15) 11 (8-14) 10 (5-14) 0.346 Pattern of relapse < 0.001 (0.062) Locoregional 14 (4.7) (63.6) 4 (6.9) (30.8) Distant 8 (2.7) (36.4) 9 (15.5) (69.2) Figure 1. Comparison of overall survival and event-free survival in two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Figure 1. Comparison of overall survival and event-free survival in two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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Mir-671-5p, Mir-193b-5p, Mir-1307-5p Are Useful for Predicting Outcome in Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood-2021-150245 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2399-2399

Author(s):

Aditi Sharma ◽

Ashim Das ◽

Amanjit Bal ◽

Radhika Srinivasan ◽

Pankaj Malhotra ◽

...

Keyword(s):

Progression Free Survival ◽

B Cell Lymphoma ◽

Transcriptome Profiling ◽

Roc Curves ◽

Differentially Expressed ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Differentially Expressed Mirnas ◽

Pre Treatment

Abstract Background: Diffuse large B-cell Lymphoma (DLBCL) is stratified histologically as GCB and ABC phenotypes based on Hans algorithm. Besides this categorization, there is a paucity of molecular markers useful for predicting response to CHOP/R-CHOP chemotherapy and outcome of DLBCL patients. We performed miRNA profiling to identify potential miRNAs for their ability to predict response to chemotherapy and outcome in DLBCL patients. Methods: A total of 41 cases of histologically and immunohistochemically confirmed DLBCL cases who received R-CHOP/CHOP were included in this study after IRB approval. The follow up ranged from 7 to 2273 days with a mean of, 874 days. Cases in sustained complete remission for ≥ 1095 days were identified as "responders" whereas cases with partial response/stable disease or primary progressive disease were identified as"non-responders". In the first part of the study, miRNA transcriptome profiling was performed from lymph node tissue of 10 cases of DLBCL which included 3 responders and 7 non-responders (3 with refractory disease and 4 with relapse) for identification and selection of differentially expressed miRNAs. Total RNA was isolated from the biopsies, libraries constructed with ION TOTAL RNA-SEQ v2 and sequenced on S5 ION Torrent. The filtered reads were aligned to the reference genome hg19 using Bowtie. Differentially expressed miRNAs were identified by DESeq2. In the second part of the study, validation of the selected miRNAs was performed in a retrospective validation cohort of 41 cases including 17 responders and 24 non-responders by semi-quantitative qRT-PCR. ROC curves were obtained and best cut-off for the delta Ct values was selected for each of the miRNAs to distinguish the two cohorts of patients. In the third part of the study, an additional 38 cases of DLBCL were included prospectively as testing cohort, in whom mi-RNA were isolated from paired pre-treatment biopsy and plasma samples were evaluated for the expression of the selected miRNAs for prediction of response to treatment and outcome. Results: miRNA transcriptome profiling revealed a total of 30 differentially expressed miRNAs among DLBCL responders vs non-responders and the data was submitted to GEO database (GSE179760). The top 4 significantly downregulated miRNAs in non-responders selected for validation included miR-193b-5p, miR-671-5p, miR-1307-5p and miR-326 as shown in the volcano plot and heatmap in Fig.1. In-silico prediction for the interacting genes of the selected miRNAs revealed genes involved in lymphoma progression and chemoresistance . Validation by qRT-PCR revealed significant down-regulation of miR-1307-5p, miR-671-5p and miR-193b-5p in the non-responders compared to responders (Fig.2). There was no significant association of miRNA expression with disease stage, nodal or extranodal origin and the presence of B symptoms. However, the downregulation of miR-671-5p was found to be associated with the presence of B-symptoms. Downregulation of miR-193b-5p, miR-671-5p, miR-1307-5p expression showed a significant association with progression free survival as shown in Fig.3 (Spearman's correlation plot and Kaplan-Meier survival curves). In the prospective cohort of 38 DLBCL patients, all 3 miRNAs were expressed in cell free plasma and tissue but only miRNA-193b-5p showed correlation between them. Using the cut-off Ct values obtained from ROC curves of tissue miRNA levels in the validation cohort , 16/38 patients were predicted to be non-responders. The preliminary data showed that 8 of these 16 cases were correctly predicted (6 died of disease, 2 showed partial response). The remaining cases are still under follow-up. The treatment response could not be predicted on the corresponding plasma levels. Conclusion: Downregulation of miRNA-671-5p, miR-193b-5p and miR-1307-5p in pre-treatment biopsy samples is associated with poor outcome and shorter progression free survival and poor treatment response leading to refractory/relapse DLBCL, which needs confirmation in larger studies. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Similar Quality of Life with 5mg Versus 25mg Lenalidomide Maintenance after First-Line High-Dose Therapy and Autologous Blood Stem Cell Transplantation for Multiple Myeloma: Results of the Lenamain Trial

Blood ◽

10.1182/blood-2018-99-110977 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2003-2003 ◽

Cited By ~ 1

Author(s):

Amelie Boquoi ◽

Aristoteles Giagounidis ◽

Hartmut Goldschmidt ◽

Michael Heinsch ◽

Mathias J Rummel ◽

...

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Research Funding ◽

High Dose ◽

Event Free Survival ◽

Advisory Committees ◽

Free Survival ◽

Travel Grant ◽

Grade 3

Abstract Introduction The LenaMain study is a prospective, randomized, open label, multicenter phase III trial which included 188 patients 3 months after first-line high dose treatment and autologous stem cell transplantation (NCT number: NCT00891384). Patients were equally randomized to receive either 25 (n = 94, arm A) or 5 mg (n = 94, arm B) lenalidomide maintenance until disease progression following a uniform 6 months of 25 mg lenalidomide consolidation. Final analysis after follow-up of 46.7 months was presented at ASCO 2018 (#8016) demonstrating an extended event-free survival for arm A (11.8 months, p=0.032) and an about 10% increase of grade 3/4 infections per year as main toxicity. Here we report analysis of quality of life (QoL) data as secondary endpoint of the study. Materials & Methods The EORTC Quality of Life Questionnaire C30 (QLQ-C30) was collected at baseline and then monthly at every new cycle. The Global Health Status/Quality of Life (GHS/QoL) scale, the utility score and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. Results Baseline questionnaire compliance was excellent (95.7%) and declined over time (82%, 76%, 71%, 54%, 49% after consolidation and after year 1, 2, 3 and 4 of maintenance, respectively). At baseline, GHS/QoL (67/67) and utility (0.73/0.72) scores for arm A/B were generally high and did not differ between both arms. The median GHS/QoL change between consolidation baseline and maintenance baseline was -1%. GHS/QoL scores appear constant for both treatment arms at most time points in the first 2 years of maintenance. Relevant improvements ≥ 5 points were observed in 30% of patients while improvements ≥ 15 points were observed in 20% of patients. During the same time a similar percentage of patients had relevant ≥ 5 and ≥15 point deteriorations, with a general tendency for a slight increase at the end of year 2. Notably, a greater number of deteriorations was found in the 5 mg lenalidomide arm. Mean GHS/QoL was constant during maintenance with a slight decrease of <2 over the 1st year, reaching borderline relevance after the 2nd year with a mean change of -6 which was mainly driven by the 5 mg lenalidomide treatment arm (25 mg arm: -4 vs. 5 mg arm: -8). Utility values remained constant during maintenance (change from baseline 0.003, p=0.9 at year 1; 0.02, p=0.7 at year 2) and the overall pattern in the change over time does not appear to show any clear differences between the two treatment arms. Looking at QLQ-C30 subgroup domains after two years of maintenance, we observed a significantly higher change from baseline for diarrhea in the 25 mg lenalidomide arm, which may be a long-term drug-related effect. Conversely, role functioning was also significantly better in patients treated within the 25 mg lenalidomide arm. Other subgroups did not show significant differences after the second year. Overall GHS/QOL scores were not significantly different in patients with CR vs. ≥ vgPR. Similarly, there was no statistical difference in patients on treatment for 1, 2, 3 or 4 years of maintenance or in patients suffering from grade 3/4 adverse events or not. Thus, neither disease activity, nor duration of treatment nor high-grade toxicity biased our results. Conclusion The LenaMain trial shows that maintenance treatment with 25 mg lenalidomide vs. 5 mg significantly prolongs event-free survival. QoL, as secondary objective, was not different between both treatment arms, even showing a trend for improved QoL in the 25 mg lenalidomide treatment arm. Thus, QoL was not governed by the higher rate of infectious toxicity during high-dose lenalidomide maintenance. Disclosures Boquoi: Amgen: Honoraria, Other: Travel grant; Bristol-Myers Squibb: Honoraria; Janssen: Other: Travel grant; Celgene: Other: Travel grant. Goldschmidt:Celgene: Consultancy, Honoraria, Research Funding; Chugai: Honoraria, Research Funding; ArtTempi: Honoraria; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; Novartis: Honoraria, Research Funding; Mundipharma: Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Adaptive Biotechnology: Consultancy. Rummel:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Honoraria; Celgene: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Symbio: Honoraria. Kroeger:Sanofi: Honoraria; JAZZ: Honoraria; Novartis: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Riemser: Honoraria, Research Funding. Mai:Celgene: Other: travel grant; Janssen: Honoraria, Other: Travel grant; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding; Onyx: Other: travel grant; Mundipharma: Other: travel grant. Kobbe:Amgen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Celgene: Honoraria, Other: Travel Support, Research Funding. Fenk:Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria, Other: Travel grant, Research Funding; Bristol-Meyers Squibb: Honoraria, Other: travel grant; Janssen: Honoraria.

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R-CHOP compared with CHOP in patients with diffuse large B-cell lymphoma (DLCL): Russian experience

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18536 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18536-18536 ◽

Cited By ~ 1

Author(s):

I. Poddubnaya ◽

E. Osmanov ◽

L. Babicheva ◽

G. Tumyan ◽

E. Sorokin ◽

...

Keyword(s):

Median Overall Survival ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Complete Response ◽

Event Free Survival ◽

Relapse Free Survival ◽

Bulky Disease ◽

Free Survival ◽

Large B Cell Lymphoma

18536 Background: R-CHOP is regarded as the best available treatment for untreated patients with aggressive and indolent B- NHL. Methods: 184 previously untreated patients with DLCL were included in retrospective study: 92 patients were treated by CHOP, 92 patients were treated by CHOP plus rituximab ( R-CHOP ). Age of patients ranged 16–87 years (median 50 years). The median follow- up was 18 months. Compared groups were balanced in all parameters. The advanced stage of disease (III-IV) at diagnosis had 66% patients treated with CHOP and 67,5 % patients treated with R-CHOP. =2 extranodal zones were initially revealed at 35% in CHOP group vs 47% in R- CHOP group. PS of 25 % patients in R-CHOP group and 30% patients in CHOP group was regarded as appropriate 3–4 degrees on ECOG. Increased LDH level was marked at 60% in CHOP-group vs 54% in R-CHOP. 29% patients in R-CHOP group and 21% patients in CHOP group had B-symptoms at diagnosis; bulky disease took place in 53% cases in R-CHOP group and 62% cases in CHOP. High IPI score had 47 % patients in CHOP-group vs 48 % in R-CHOP. Results: Complete response was achieved in 74% of the patients treated with R- CHOP, as compared to 56% of those treated with CHOP alone (p<0,05). Disease progression during treatment was reported in 25% of patients in CHOP group and 18,5% in R-CHOP group. Median overall survival in patients treated with R-CHOP was NS, in patients treated with CHOP alone was 16 months. With a median follow-up of 18 months, 29 (31,5%) events (progression - 18,5%, relapse - 10%, death - 3% ) were observed in the R-CHOP group and 48 (52%) events ( progression - 25%, relapse - 20%, death - 7%) in the CHOP group (p<0,05). Median event-free survival and relapse-free survival in the CHOP group was 12 months, in R-CHOP group NS. Toxicity was equivalent in both groups. Conclusions: We have established better direct efficiency and outcome of R-CHOP in any age of pts. No significant financial relationships to disclose.

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Impact of Organ Function–Based Clinical Trial Eligibility Criteria in Patients With Diffuse Large B-Cell Lymphoma: Who Gets Left Behind?

Journal of Clinical Oncology ◽

10.1200/jco.20.01935 ◽

2021 ◽

pp. JCO.20.01935

Author(s):

Arushi Khurana ◽

Raphael Mwangi ◽

Grzegorz S. Nowakowski ◽

Thomas M. Habermann ◽

Stephen M. Ansell ◽

...

Keyword(s):

Clinical Trial ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Event Free Survival ◽

Organ Function ◽

Eligibility Criteria ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Hazard Ratios ◽

Large B Cell

PURPOSE Exclusion of patients needing urgent treatment or requiring novel biomarkers before enrollment has impacted the ability to enroll real-world patients in frontline trials of diffuse large B-cell lymphoma (DLBCL). The impact of baseline organ function–based eligibility criteria on this effect and clinical trial exclusion is less well-understood. METHODS Consecutive patients with newly diagnosed lymphoma were enrolled from 2002 to 2015 into the Molecular Epidemiology Resource (MER) of the University of Iowa and Mayo Clinic Lymphoma Specialized Program of Research Excellence. The current analysis includes 1,265 patients with DLBCL receiving standard immunochemotherapy. Organ function parameters were identified from criteria for hemoglobin, absolute neutrophil count, platelet count, creatinine clearance, and bilirubin, as reported in frontline DLBCL trials. Abstracted laboratory values from MER were used to determine the percent (%) of patients excluded. Outcomes and cause-of-death analyses comparing ineligible and eligible groups in MER were conducted. An interactive online tool was developed to estimate exclusions based on organ function for future trial design. RESULTS Between 9% and 24% of MER patients with DLBCL receiving standard immunochemotherapy were excluded on the basis of baseline organ function alone. Ineligible patients based on organ function had significantly inferior event-free survival (hazard ratios, 1.67-2.16), overall survival (hazard ratios, 1.87-2.56), and event-free survival at 24 months (odds ratio, 1.71-2.16). Ineligible patients were more likely to die from lymphoma progression than increased therapy-related complications. CONCLUSION Current national and international trials exclude up to 24% of patients from participation on the basis of organ function alone. A significant difference in the outcomes, notably lymphoma-related death, suggests issues with generalization and potential exclusion of high-risk patients. These data will help future clinical trial development and meet US Food and Drug Administration and ASCO recommendations to increase trial accrual.

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Autologous Transplantation for Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL).

Blood ◽

10.1182/blood.v114.22.2310.2310 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2310-2310 ◽

Cited By ~ 1

Author(s):

Uday Popat ◽

Chitra Hosing ◽

Michelle Fanale ◽

L. Jeffrey Medeiros ◽

Amin M. Alousi ◽

...

Keyword(s):

Cell Lymphoma ◽

Autologous Transplantation ◽

B Cell Lymphoma ◽

Event Free Survival ◽

Peripheral Blood Stem Cells ◽

Free Survival ◽

Histologic Evidence ◽

Stem Cell Source ◽

Large B Cell Lymphoma ◽

Blood Stem Cells

Abstract Abstract 2310 Poster Board II-287 Background: NLPHL is an uncommon type of Hodgkin lymphoma characterized by nodules composed of large neoplastic B-cells (CD20+), lymphocyte predominant (LP) cells (previously known as L& H cells), associated with many small reactive B-cells. Patients with NLPHL typically have an indolent clinical course, but the disease can recur, often with histologic evidence of progression or transformation. Because of its rarity, limited information is available, mainly from retrospective studies. Very little information is available about salvage therapy particularly about the role of autologous transplantation in this disease. The purpose of this study was to evaluate outcomes of autologous transplantation in patients with relapsed or refractory NLPHL. Patients and Methods: All patients with NLPHL who underwent autologous transplantation between January 1990 and December 2008 were included in this study. Pathology specimens were reviewed. The diagnosis of NLPHL was confirmed in all cases and, at time of transplant, many patients had histologic evidence of T-cell/histiocyte rich large B-cell lymphoma. During these 19 years, 26 patients (24 males) underwent autologous transplantation. Median age at transplantation was 35 years (range 13-51). At transplantation, 9 (35%) were in complete remission (CR); 13 (50%) were in partial remission (PR); and 4 (15%) had stable (SD) or progressive disease (PD). Median number of prior chemotherapy regimens was 3 (1-4). LDH was elevated in 10 (38%). Peripheral blood stem cells were used as stem cell source in 23 (86%) patients. Conditioning regimen were BEAM(10), BEAM-R(5), CBV(6), and other regimens in 5 patients. Peripheral blood stem cells were used as stem cell source in 23 (86%) patients. Results: Following transplant, 22 patients achieved complete remission. No treatment related mortality or treatment related MDS/AML occurred. Seven patients have relapsed. With a median follow up of 50 months (range, 2-138 months), the 5-year overall (OS) and event-free survival (EFS) were 76% (SE 9%) and 69%(SE 10%), respectively. For chemosensitive patients, The 5-year overall (OS) and event-free survival (EFS) were 82% (SE 10%) and 79% (SE 10%), respectively. Three out of 4 patients (75%) with chermoresistant disease relapsed compared to 4 out of 22 (18%) of patients with chemosensitive disease. Five patients died, all of recurrent disease. Conclusion: High-dose chemotherapy and autologous transplantation is highly effective in patients with refractory NLPHL or relapsed NLPHL including patients with histologic evidence of transformation to T-cell/histiocyte rich large B-cell lymphoma, and results in long term remission in most of patients. Disclosures: No relevant conflicts of interest to declare.

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Elevated Soluble IL-2Ra Levels Are Associated With Inferior Outcome and Is Independent Of MIPI Score in Patients With Mantle Cell Lymphoma

Blood ◽

10.1182/blood.v122.21.4256.4256 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4256-4256

Author(s):

Mohamad Bassam ◽

Matthew J Maurer ◽

Mary Stenson ◽

Linda E Wellik ◽

Christine Allmer ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Newly Diagnosed ◽

Event Free Survival ◽

Free Survival ◽

Cytokine Levels ◽

Mantle Cell ◽

Pre Treatment ◽

Normal Controls

Abstract Blood cytokine elevations have been associated with non-Hodgkin's lymphoma (NHL) such as follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Although other types of NHL have been studied, to our knowledge, cytokine deregulation in mantle cell lymphoma (MCL) has not been comprehensively studied. In this study, we studied cytokine levels in untreated and relapsed MCL patients using a multiplex assay to determine the role of dysregulated cytokines in these patients and study any prognostic relevance that could be drawn from their effect on relapse and survival. Samples from two data sets of MCL patients were used for this study. The first dataset was pre-treatment serum samples from newly-diagnosed patients with MCL (n=88) from the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource. The second dataset included pre-treatment plasma samples from relapsed MCL patients (n=20) treated on the MC0048G clinical trial studying the effect of everolimus in lymphoma patients. In addition, unrelated controls from a case-control study of lymphoma were included (n=15 serum, n=24 plasma). Thirty cytokines were assessed using a multiplex ELISA. Differences between cytokines in cases and controls were assessed using Wilcoxon rank-sum tests; associations between cytokines and event-free survival were assessed using Kaplan-Meier curves and Cox proportional hazards models. In the newly diagnosed MCL patients, IL-10 (p<0.0001), IL-1RA (p=0.001), IL-6 (p= 0.04), sIL-2Rα (p=0.005), and MIG (p=0.002) were elevated compared to normal controls. The only significantly elevated cytokine in the recurrent MCL cases compared to controls was sIL-2Rα (p= 0.0006). High levels (above median) of sIL-2Rα levels were associated with inferior event-free-survival (EFS) in both newly diagnosed (HR=2.61 (95% CI: 1.41-4.81, p= 0.0022) and relapsed MCL (HR=2.90, 95% CI: 1.08-7.80, p=0.035) patients; this remained significant after adjusting for MIPI (p=0.01 and 0.03, respectively). Moreover, in the relapsed MCL group eotaxin (p< 0.0001), IL-12 (p< 0.0001), and MCP-1 (p= 0.0002) were suppressed compared to normal controls. We hypothesized that STAT3 (pSTAT3) in MCL cells might be the possible cause behind IL-12 suppression. Indeed, 12/13 MCL samples from IL-12-suppressed relapsed MCL patients were pSTAT3+. When studying the association between cytokine levels and clinical characteristics in both untreated and relapsed MCL groups, sIL-2R was significantly associated with the MIPI score in both untreated (p<0.0001) and relapsed (p=0.007) MCL groups; and with performance status (p=0.005), lymphoma stage (p=0.004), and B symptoms (p=0.006) in the newly diagnosed MCL group.Figure 1Event-free survival of patients with untreated and relapsed MCL by sIL-2R levels.Figure 1. Event-free survival of patients with untreated and relapsed MCL by sIL-2R levels. Our study shows that cytokines are deregulated in both untreated and relapsed MCL patients. It emphasizes on the importance of sIL-2R in its association with negative clinical parameters and worse prognosis in MCL. These findings gives the rational for using sIL-2R along with MIPI and other parameters in predicting prognosis and further to monitor response in MCL. Furthermore, we showed that IL-12 is suppressed in relapsed MCL group and that pSTAT3 expression is a possible mechanism behind this suppression. Further studies are needed to investigate the effect of drugs that suppress pSTAT3 expression in IL-12 suppressed MCLs and disease progression in relapsed MCL patients. Disclosures: No relevant conflicts of interest to declare.

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High Risk Diffuse Large B Cell Lymphoma: A Comparison of Aggressive Subtypes Treated with Dose Adjusted Chemotherapy-the University of Texas MD Anderson Experience

Blood ◽

10.1182/blood.v128.22.106.106 ◽

2016 ◽

Vol 128 (22) ◽

pp. 106-106 ◽

Cited By ~ 3

Author(s):

Vishwanath Sathyanarayanan ◽

Yasuhiro Oki ◽

Amir K Issa ◽

Mohamed Amin Ahmed ◽

Mansoor Noorani ◽

...

Keyword(s):

High Risk ◽

Board Of Directors ◽

Research Funding ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Time To Event ◽

Advisory Committees ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Md Anderson

Abstract Background: Diffuse large B cell lymphoma (DLBCL) is the most common type of non Hodgkin lymphoma (NHL).Nearly 50% of high-risk DLBCL patients are not cured with standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP). High risk DLBCL may be defined as double hit lymphoma (DHL, translocation of MYC and BCL2 or BCL6), double expressor lymphoma (DEL, over expression of MYC and BCL2), high risk international prognostic index (IPI) of 3-5, high Ki-67, and non-germinal center subtype (non-GCB). The majority of DHL cases occur in the GCB subtype, as opposed to the majority of DEL cases which occur in non-GCB. Hence we sought to compare different high risk subsets treated with dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and rituximab (DA) EPOCH-R. In single arm phase II clinical trials, dose adjusted (DA) EPOCH-R has shown promising results, with potential greater efficacy in the GCB subtype in subset analyses (Wilson et al, Hematologica 2012). A randomized phase III study comparing RCHOP with (DA) EPOCH-R in newly diagnosed DLBCL has completed accrual, with highly anticipated results due in late 2016. Methods: We conducted a retrospective reviewof all consecutive, newly diagnosed DLBCL patients treated with (DA) EPOCH-R at MD Anderson Cancer Center from 2010 to 2014. Eligible patients were 18 years or greater, had high-risk DLBCL as determined by the treating physician, and had available data of treatment and response. The cell of origin subtype was determined by immunohistochemistry using Hans algorithm, and MYC and BCL2 positivity were defined as BCL2 positive in at least 70% and MYC positive in at least 40% of cells. DHL was defined as rearrangement of MYC and BCL2 or BCL6 by fluorescent in situ hybridization. The objectives were to analyze demographic, prognostic, and treatment variables in comparison with clinical response and survival outcomes in three sub groups which included 1. DHL (GCB) 2. DLBCL without MYC and BCL2 expression (GCB), and 3. DEL (GCB and non GCB). Complete response (CR), overall survival (OS) and progression free survival (PFS) were calculated using standard methods. Statistical analysis was done using Fishers exact test or Chi-square test / Kruskal-Wallis test. Kaplan-Meier method was used for time-to-event analysis including overall survival and progression free survival. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Results: We identified 233 high risk DLBCL patients treated with (DA) EPOCH-R. After filtering the data to identify patients which were included in our three groups, we identified 22 patients with DHL (GCB), 46 patients with non DEL (GCB), and 16 with DEL. The demographic features and outcomes are mentioned in the table 1 below. The DHL group had more frequent bone marrow (BM) involvement, and the DHL and DEL groups were more frequently age >60 years and high IPI in comparison to the non DEL GCB group. The CR rate, OS and PFS at 1 year were not significantly different between these three groups. Figure 1 highlights the OS (A) and PFS (B) results of each group. Conclusions: (DA) EPOCH-R is highly effective in patients with subsets of patients with high-risk DLBCL and may be able to overcome prognostic factors which have been shown to be adverse with RCHOP therapy. The results of this retrospective study suggest that OS in DHL, DEL and non DEL (GCB) are not statistically different. Hence, intensive chemotherapy with (DA) EPOCH-R could be considered as a frontline treatment option for patients with high risk DLBCL, pending further confirmation in randomized trials. Disclosures Oki: Novartis: Research Funding. Fowler:Infinity: Consultancy, Research Funding; Roche: Consultancy, Research Funding; TG Therapeutics: Consultancy; Celgene: Consultancy, Research Funding; Jannsen: Consultancy, Research Funding; Gilead: Research Funding. Wang:Pharmacyclics: Research Funding; Juno Therapeutics: Research Funding; Acerta Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; BeiGene: Research Funding; Kite Pharma: Research Funding; Onyx: Research Funding; Asana BioSciences: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Fayad:Seattle Genetics: Consultancy, Research Funding. Westin:ProNAi: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Chugai: Membership on an entity's Board of Directors or advisory committees.

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