The Predictive Value of FCGR3A Polymorphism on Clinical Outcomes of Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP Chemotherapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 89-89
Author(s):  
Steven I. Park ◽  
Amy S. Lucas ◽  
Michael Kingberg ◽  
Dominic Moore ◽  
Michael Chiu ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Predictive Value ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
B Cell Lymphoma ◽  
Published Data ◽  
Chop Chemotherapy ◽  
Large B Cell Lymphoma ◽  
Significant Difference

Abstract Abstract 89 BACKGROUND: The predictive value of biomarkers for diffuse large B-cell lymphoma (DLBCL) remains controversial especially in the rituximab era. FC-γ receptor 3A (FCGR3A) genotype has emerged as a potential biomarker for rituximab response, supported by the data that antibody-dependent cell-mediated cytotoxicity (ADCC) plays a major role in rituximab-induced cell death. Preclinical data have demonstrated that effector cells homozygous for valine (V) at the rs396991 single nucleotide polymorphisms (SNP) of FCGR3A gene bind the Fc portion of rituximab with significantly higher affinity than those homozygous for phenylalanine (F). In addition, the stronger binding of the V isoform produces more effective ADCC in vitro. Although some recent studies have suggested better clinical outcomes associated with certain FCGR3A genotypes, no published data to date have shown any definitive association between FCGR3A polymorphism and survival outcomes in DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). In the present study, we evaluated the predictive value of FCGR3A polymorphism to determine whether FCGR3A genotype could potentially predict survival outcomes in DLBCL patients treated with R-CHOP. PATIENTS AND METHODS: A total of 72 patients with newly diagnosed DLBCL treated at the University of North Carolina, Chapel Hill were analyzed. All patients received R-CHOP chemotherapy. Genomic DNA was isolated from archival formalin-fixed paraffin-embedded tissues and genotyped in the IPIT Molecular Genomics facility at UNC. Using Sequenom iPlex genotyping assays, the genotypes of the rs1801274 (FCGR2A) and rs396991 (FCGR3A) SNP were obtained. For both assays, greater than 90% of the samples produced unambiguous genotypes. RESULTS: The distribution of the V/V, V/F, and F/F FCGR3A genotypes was 17%, 33%, and 50%, respectively. The frequency of the F/F genotype was somewhat higher in this study population compared to other previously published data. There was no significant difference between the F/F group and the non-F/F (V/V or V/F) group in patient characteristics, including age, race, gender, stage, the International Prognostic Index (IPI) score, LDH, and performance status. Approximately 55 to 60% of the patients had stage III or IV disease. Patients in the F/F group had an overall response rate (ORR) of 73% with a complete response rate (CRR) of 58% while ORR and CRR were 91% and 73%, respectively, in the non-F/F group (p = ns). A significant difference in survival outcome was observed between the F/F and non-F/F patients with a median follow-up of 30 months. According to Kaplan-Meier estimates, overall survival rates (OS) were 72% and 96% in the F/F and non-F/F groups, respectively, at 24 months (Figure 1, p=0.02). Furthermore, the progression-free survival rates (PFS) at 24 months were 41% and 85% in the F/F and non-F/F groups, respectively. (Figure 1, p=0.002). Approximately 59% of the F/F patients relapsed with the median time to progression (TTP) of 30 months while only 15% of the non-F/F patients relapsed with the median TTP not reached during this followup (p=0.01). Multivariable Cox regression analyses were performed to further investigate the predictive value of FCGR3A polymorphism. The IPI score had prognostic impact for OS and PFS as expected, and both the IPI and FCGR3A genotype were independently associated with clinical outcomes. In contrast, FCGR2A polymorphism had no predictive value in the same patient population. CONCLUSIONS: This study suggests that FCGR3A polymorphism has predictive significance independent of IPI in DLBCL patients treated with R-CHOP. FCGR3A genotypes based on F/F versus non-F/F status could potentially be used to predict clinical outcomes in this patient population. A confirmatory analysis is being planned using blood samples from a large prospective trial. Disclosures: Park: Cephalon: Research Funding; GlaxoSmithKline: Research Funding.

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 ◽  
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.

scholarly journals Management of Elderly Patients with Diffuse Large B-Cell Lymphoma in a Network of Community Oncology Practices in the United States

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4215-4215
Author(s):  
John M Burke ◽  
Jenny L Black-Shinn ◽  
Jamyia Clark ◽  
Jennifer Frytak ◽  
Janet Espirito ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Research Funding ◽  
Chart Review ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Chop Chemotherapy ◽  
Eligibility Criteria ◽  
Large B Cell Lymphoma ◽  
Community Oncology

Abstract Introduction: Treatment patterns and clinical outcomes in elderly patients with DLBCL treated outside of clinical trials are poorly characterized. A previous report from Medicare Claims data found that 28% of patients above the age of 66 were treated with rituximab monotherapy or were not treated at all, with corresponding median survival of 18 and 2 months, respectively (Hamlin PA et al., Oncologist 2014; 19:1249-57). We conducted a retrospective chart review of diffuse large B cell lymphoma (DLBCL) patients diagnosed and managed within a community oncology practice network to evaluate treatment patterns and corresponding clinical outcomes. Methods: This was a retrospective observational chart review study of patients aged 60 years and over with newly diagnosed DLBCL. Eligibility criteria required a diagnosis between 1/1/2011 and 12/31/2012, with follow up through 12/31/14, plus no prior therapy for DLBCL. Data were obtained via programmatic query of the US Oncology Network/McKesson Specialty Health electronic health record database. Manual chart review was then performed on a subset of patients (n = 301) to confirm initial findings and gather additional information. Structured data elements were evaluated in univariate and multivariable logistic regression analysis in the subset of patients with stage 2 to 4 disease in order to determine factors associated with treatment with standard R-CHOP. Overall survival (OS) and progression free survival (PFS) were estimated from treatment initiation using the Kaplan Meier (KM) method. Results: 1151 patients who fit the eligibility criteria were identified. Age significantly influenced frontline treatment selection. Table 1 lists the percentage of patients with stage 2 to 4 disease treated with various regimens by age cohorts. "R-CHOP Alternative" was defined as one of the following: less than 6 cycles of R-CHOP, < 80% of full doses of agents in R-CHOP, or use of an alternative regimen like R-CVP, R-CEOP, or bendamustine-R. In multivariable analysis, age (OR=4.07 for age 65-79 and OR=7.98 for age 60-64; p<0.0001), ECOG 0-1 (OR=2.44, p=0.1380), geographic practice region other than south (OR=1.96, p=0.0002), body mass index (OR=2.52 for underweight/normal and OR=1.93 for overweight, p<0.0001 compared to obese), increased albumin (OR=1.49, p=0.0046), and increased bilirubin (OR=0.56, p=0.0081) were identified as clinically relevant predictors of the likelihood of receiving standard R-CHOP chemotherapy. Patients with a documented history of cardiomyopathy, congestive heart failure, EF < 50%, chronic renal insufficiency, or diabetes had a reduced prevalence of receiving standard R-CHOP chemotherapy compared with patients with none of those risk factors (34.3% versus 51.2%, p = 0.0640). Median PFS in the R-CHOP, attenuated R-CHOP, and rituximab monotherapy groups was 51.5 months, 11.0 months, and 8.6 months, respectively. 12- and 24-month OS with standard R-CHOP, R-CHOP alternative, and rituximab monotherapy were 90% and 80%, 78% and 64%, and 74% and 47%, respectively. 2-year OS for patients with IPI 0-2 and IPI ≥3 was 80% and 58%, respectively. Conclusions: As patients with newly diagnosed DLBCL get older, fewer receive standard R-CHOP chemotherapy. Age, performance status, albumin, bilirubin, cardiac and renal function, and the presence of diabetes mellitus affect ability to receive standard R-CHOP. Aggressiveness of treatment correlates with clinical outcomes. Disclosures Burke: Incyte: Consultancy; Janssen: Consultancy; Pfizer: Consultancy; TG Therapeutics: Other: Travel Expenses; Millenium: Consultancy. Black-Shinn:McKesson Specialty Health: Employment. Clark:McKesson Specialty Health: Employment. Frytak:McKesson Specialty Health: Employment, Equity Ownership. Espirito:McKesson Specialty Health: Employment. Sharman:Acerta: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Pharmacyclics: Research Funding; TG Therapeutics: Research Funding; Seattle Genetics: Research Funding.

Therapeutic Comparision of Surgical Resection Followed by R-CHOP and R-CHOP Alone for Primary Localized Intestinal Diffuse Large B Cell Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1627-1627 ◽  
Author(s):  
Ho Sup Lee ◽  
Lee Chun Park ◽  
Eun Mi Lee ◽  
Seong Hoon Shin ◽  
Byeong Jin Ye ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Survival Rate ◽  
B Cell ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Surgery Group ◽  
Significant Difference ◽  
Large B Cell

Abstract Abstract 1627 Abstract Background: Gastrointestinal tract is the most commonly involved extranodal site and is represented 10–15% of all non-Hodgkin¡&hibar;s lymphoma (NHL) cases and 30–40% of all extranodal sites. In this retrospective studies, the purpose is finding appropriate treatment strategy according to comparing the efficacy of treatment in patients with primary intestinal diffuse large B cell lymphoma (DLBL) undergoing surgery followed chemotherapy or chemotherapy alone. Method: Seventy six patients were newly diagnosed with DLBL and received chemotherapy between March 2004 and June 2011. Primary intestinal lymphoma which had predominant intestinal lesions was diagnosed by specialized hemato-oncologist. All patients were treated with rituximab combined cyclophosphamide, adriamycin, vincristine, and prednisolone (R-CHOP). Patients were divided into two groups. One included patients who were undertaken surgery followed by R-CHOP (surgery group). The other included patients who were undertaken R-CHOP alone (CT group). Results: The characteristics of the patients were as follows: the median age was 56.5 years (range 15–85 years) with a female-to-male ratio of 45: 31. Patients characteristics had no significant difference between two groups. The estimated 3 years progrression free survival rates (PFS) and overall survival rates (OS) of surgery and CT group were 92.2% and 74.8%, (p=0.009) and 94.2% and 80.7%, (p=0.049) respectively. In univariate analysis, PFS and OS were estimated in Lugano stage I, II1 and II2, IIE (p=0.006 and p=0.036), Low, Low-intermediate, and high-intermediate risk (p=0.004 and p=0.000), and surgery and CT alone, (p=0.009 and p=0.049), respectively. In multivariate analysis, there was no independent predictive factors for survival. Conclusion: Patients treated with surgery followed by R-CHOP were seemed to have higher survival rate than R-CHOP alone although there was no significant differences for survival rate. There was no significant prognostic factors for survival but there were possible prognostic factors such as Lugano stage, IPI risk, and treatment modality for PFS and OS. Figure. The superior survival rates were shown in surgery group than those in R-CHOP chemotherapy group. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinicopathological Correlation with Outcome of Diffuse Large B Cell Lymphoma: Experience in a Specialized Cancer Care Centre in Bangladesh

2021 ◽  
Vol 22 (1) ◽  
pp. 3-6
Author(s):  
Tamanna Bahar ◽  
Zulfia Zinat Chowdhury ◽  
Shaila Rahman ◽  
Salina Haque ◽  
AKM Mynul Islam ◽  
...  
Keyword(s):  
Retrospective Study ◽  
B Cell ◽  
Cancer Care ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Care Centre ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in the world, and accounts for 30%–40% of all adult NHLs. It is clinically, morphologically and genetically a heterogeneous group of tumors composed of large B cells. This study aimed to determine the clinical features, treatment options, the response rate in a specialized cancer care centre. Methods: This retrospective study included all DLBCL patients registered in the department of Haematology of National Institute of Cancer Research and Hospital (NICR&H), Bangladesh between July 2016 to June 2019. Results: A total of 151cases were included in this study. The mean age was 47 years with a standard deviation (SD) of 15 years. Males (66.2%) were more in the occurrence of DLBCL. We divided the cases into three different entities of DLBCL and non-germinal centre B (non-GCB) variety was the prevalent (46.4%) one. Several types of first-line chemotherapy were used in management and the overall response rate (ORR) was 76.6% and 9.2% of death. The response was found to be significant with B symptoms, stage, and international prognostic index (IPI) score. But no significant difference was observed in outcome among different types of DLBCL after treatment. Conclusion: This retrospective study will help to ascertain the co relation of DLBCL outcome with clinicopathological profile. (edited) J MEDICINE JAN 2021; 22 (1) : 3-6

Decreased Brain FDG Uptake in Patients with Diffuse Large B Cell Lymphoma (cold brain) Is Associated with High Risk Disease and Predicts Poor Response to R-CHOP Chemotherapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1593-1593
Author(s):  
Meghana Raghavendra
Keyword(s):  
Response Rate ◽  
Complete Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Pet Scan ◽  
Chop Chemotherapy ◽  
Fdg Uptake ◽  
Large B Cell Lymphoma ◽  
The Right

Abstract 1593 Background: Decreased 2-deoxy-2-(18F)fluoro-D-glucose (FDG) uptake by brain tissue, (henceforth “cold brain”) has been occasionally described in the literature in patients with bulky solid tumors. There is currently no data describing brain FDG uptake on positron emission tomography (PET) scan in patients with diffuse large B cell lymphoma (DLBCL) and its association with clinical characteristics as well as prognosis. Method: We retrospectively analyzed clinical data from 110 patients with histologically confirmed DLBCL diagnosed between November 1, 2004 and December 31, 2011. Initial staging PET scans prior to treatment were reviewed. Brain FDG uptake on PET scan was analyzed by an expert nuclear radiologist. Qualitative determination of cold versus normal brain activity was made relative to usual distribution and metabolism. Secondarily, a region of interest cursor was placed on the right basal ganglia for a quantitative standard uptake value (SUV) measurement. In cases where measurement of the right basal ganglia was not possible, the cerebellum was used. Patient characteristics were compared using Fisher's exact test. Survival analyses were performed using Kaplan-Meier curves and compared using log-rank test. Cox proportional regression model was used for multivariate analyses. Results: We included 110 patients in the study. Twenty patients (18%) had cold brain by initial PET scan. The cold brain subgroup had a median age of 72.5 years (range, 46 to 85) and 55.0% were males. Cold brain was associated with higher rates of stage III/IV disease (80.0% vs 52.2%; P = 0.026), International Prognostic Index (IPI) score of ≥3 (85.2% vs. 36.7%; P = 0.0001), and > 1 extranodal sites of involvement (50.0% vs. 26.7%; P = 0.059) compared to the non-cold brain subgroup. Among patients who received rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone chemotherapy (R-CHOP), those with cold brain had a lower complete response rate (44.0% vs. 86.0%; P = 0.030), shorter progression-free-survival (PFS) (4.5 months vs. 9.1 months; P = 0.06), but similar overall survival (OS) (47.9 months vs. 58.4 months; P = 0.26). After adjusting for IPI, patients with cold brain seemed to have a shorter PFS compared to those without cold brain, although this was not statistically significant (hazard ratio: 3.13; 95% CI: 8.20-1.22; P = 0.096). Conclusion: In our study, cold brain was a phenomenon frequently observed among patients with newly diagnosed DLBCL. It was associated with higher risk disease, lower complete response rate to R-CHOP chemotherapy, and potentially shorter PFS. Further studies in larger patient population are needed to determine its true prognostic significance. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Comparison of 2-year outcomes with CAR T cells (ZUMA-1) versus salvage chemotherapy in refractory large B-cell lymphoma

2021 ◽  
Author(s):  
Sattva S. Neelapu ◽  
Frederick L. Locke ◽  
Nancy L. Bartlett ◽  
Lazaros John Lekakis ◽  
Patrick Reagan ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Clinical Outcomes ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Pivotal Phase ◽  
Large B Cell Lymphoma ◽  
Car T ◽  
Large B Cell

The SCHOLAR-1 international retrospective study highlighted poor clinical outcomes and survival among patients with refractory large B-cell lymphoma (LBCL) treated with conventional chemotherapy. Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, demonstrated durable responses in patients with refractory LBCL in the pivotal phase 1/2 ZUMA-1 study (NCT02348216). Here, we compared SCHOLAR-1 with the 2 year outcomes of ZUMA-1. Prior to comparison of clinical outcomes, propensity scoring (based on a broad set of prognostic covariates) was used to create balance between ZUMA-1 and SCHOLAR-1 patients. In the pivotal phase 2 portion of ZUMA-1, 101 patients received axi-cel and were evaluable for response and survival. In SCHOLAR-1, 434 and 424 patients were evaluable for response and survival, respectively. ZUMA-1 patients were more heavily pretreated than SCHOLAR-1 patients. The median follow-up was 27.1 months in ZUMA-1. The objective response rate and complete response rate were 83% and 54% in ZUMA 1 vs 34% and 12% in SCHOLAR-1, respectively. The 2-year survival rate was 54% in ZUMA-1 and 20% in SCHOLAR-1, and a 73% reduction in the risk of death was observed in ZUMA-1 vs SCHOLAR-1. These results were consistent with those of an additional standardization analysis in which strata were limited to 2 prognostic factors (refractory categorization and presence/absence of stem cell transplant after refractoriness to chemotherapy) to conserve sample size. Despite the limitations of a nonrandomized analysis, these results indicate that axi-cel produces durable responses and a substantial survival benefit versus non-CAR T-cell salvage regimens for patients with refractory LBCL.

Independent Predictive Value of PET-CT Pre Transplant in Relapsed and Refractory Patients with CD20 Diffuse Large B-Cell Lymphoma (DLBCL) Included in the CORAL Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 881-881 ◽  
Author(s):  
Marek Trneny ◽  
Andre Bosly ◽  
Krimo Bouabdallah ◽  
David Ma ◽  
Ofer Shpilberg ◽  
...  
Keyword(s):  
B Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Pet Scan ◽  
Factors Affecting ◽  
Early Relapse ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Abstract Abstract 881 Salvage chemotherapy followed by high dose therapy and autologous stem cell transplantation (ASCT) is the standard of treatment for chemosensitive relapses in diffuse large B cell lymphoma. The CORAL trial compared the association rituximab, ifosfamide, etoposide, carboplatinum, R-ICE to rituximab dexamethasone Cytarabine and cisplatinum R-DHAP and factors affecting outcome. Methods: DLBCL CD 20+ in first relapse or pts refractory after first line therapy were randomized between R-DHAP and R-ICE. Response was evaluated according to Cheson Criteria (1999); chemosensitive patients after 3 cycles received BEAM and ASCT, and were randomized between observation and maintenance with rituximab for 1 yr. PET scan was not required at the time of design of the study but recommended, whenever possible. Consequently, the assessment of response with PET scan was also performed in a subset of patients and could be compared to revised Cheson criteria (2007). Results: Intent to treat analysis was made on 394 pts ( 201 R ICE arm, 193 R DHAP arm) and was reported earlier this year (J Clin Oncol 27:15s, 2009 (suppl; abstr 8509). There was no difference between the two treatments arms. Prospectively, 123 pts with PET scans were recorded at the end of induction treatment and were reported by investigators positive or negative. Functional imaging was not used to modify treatment protocol. PET was negative ( FDG non-avid) in 61 pts and positive ( FDG-avid) in 62 pts; 60 and 58 pts completed 3 cycles of R-ICE or R-DHAP; 50 PET-ve and 26 PET +ve pts received BEAM respectively. Median age 54 yrs.; 52 relapses >12 months, 71 refractory/early relapses <12 months; 77 pts had prior exposure to rituximab; secondary IPI 0-1 77 pts, sIPI 2-3 40 pts. The overall response rate was 74%, with 47% complete remission. The number of CR, CRu, PR were 42,11,7 in PET negative pts and 1,4,26 in PET positive pts respectively. There was a highly significant difference (p<0.0001) in response rate per CT for PET negative 98% (CI 91-100%) vs. PET positive 50% (CI 37-63%) patients. Thus using updated criteria with PET, all the patients negative, except one stable, should be now characterized as complete responders. Whereas, only 5 pts PET positive were recorded to be in CR or CRu. No histology was available. For the whole population, three years EFS was 30%. EFS were different in pet negative pts 40% vs. 16% for positive pts ( p<0.0001). The same significant difference was found for PFS 43% vs. 28% respectively. Three years overall survival was 47%, for pts PET-ve 66% vs. pts PET+ve 49% ( p=0.007). For the 26 patients submitted to transplantation with PET positivity there was a significant difference for EFS (p=0.03) when compared to PET negative patients, but no statistical difference in PFS and OS. Factors affecting response rate in multivariate analysis were early relapse/refractory < 12 months and PET+ve following induction. The same factors were found in cox's model for EFS and PFS. Conclusion: This prospective study in relapsing DLBCL shows that PET scan is accurate to predict outcome. PET is an independent predictive factor with early relapse/refractory <12 months. A PET positivity pretransplantation is associated with a poor outcome and argues for new therapeutic approaches in this population. Disclosures: No relevant conflicts of interest to declare.

The Impact of Concurrent Expression of MYC and BCL2 on Outcomes of Localized Primary Gastric Diffuse Large B-Cell Lymphoma Undergoing Rituximab-Containing Chemotherapy with or without Radiotherapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1761-1761
Author(s):  
Akihisa Kawajiri ◽  
Dai Maruyama ◽  
Akiko Miyagi Maeshima ◽  
Shin-ichi Makita ◽  
Hideaki Kitahara ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
B Cell Lymphoma ◽  
Good Prognosis ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
The Impact ◽  
Large B Cell ◽  
Overall Survival Rates

Abstract Introduction Although the Japanese multicenter phase II trial in localized primary gastric diffuse large B-cell lymphoma (PG-DLBCL), which evaluated three cycles of CHOP followed by radiotherapy (RT), showed good prognosis (Cancer Sci 2005; 96: 349), reports about outcomes and prognostic factors of localized PG-DLBCL patients in the rituximab era are limited. Recently, it has been reported that the concurrent expression of MYC and BCL2 predicts unfavorable outcome in DLBCL patients treated with R-CHOP (J Clin Oncol 2012; 30: 3460). However, the impact of the concurrent expression of MYC and BCL2 on outcomes of localized PG-DLBCL patients has never been reported. Patients and Methods We retrospectively analyzed 52 consecutive patients diagnosed as having localized (stage I or II according to the Lugano Staging System for Gastrointestinal Lymphomas) PG-DLBCL who were initially treated at our institution between 2003 and 2013. Positivity of MYC in immunohistochemistry was defined as labeling of tumor cells of more than 40% and positivity of BCL2 was defined as more than 70%. The lymphoma cells were assigned a GCB or non-GCB phenotype using the Hans algorithm for determining the cell-of-origin (COO) subtyping. Results Twenty-four (46%) patients were male and 28 (54%) female, with a median age of 62 years (range: 29-85). Thirty (58%) patients presented with stage I disease, 15 (29%) with stage II1, two (4%) with stage II2 and five (9%) patients with stage IIE. Most patients (47 patients; 90%) had low or low-intermediate risk based on the International Prognostic Index. Fifty (96%) patients received R-CHOP with or without RT, and one each received CHOP plus RT, and total gastrectomy followed by rituximab. The median number of CHOP cycles was three (range: 2-8). The majority (43 patients; 83%) of patients were treated with R-CHOP followed by RT. COO subtype could be determined in 48 of the 52 patients (63% GCB and 37% non-GCB). Both MYC and BCL2 expression could be assessed in 47 of the 52 patients, and the concurrent expression of MYC and BCL2 was confirmed in seven (15%) patients. In this analysis, no patients showed positivity for EBER-1 in situ hybridization, which was reported as an adverse prognostic factor of localized PG-DLBCL in the pre-rituximab era. Median follow-up duration was 76 months (range: 4-127 months). Fifty (96%) patients achieved complete responses, and the remaining two without concurrent expression of MYC and BCL2 had primary refractory disease. The estimated 5-year overall and progression-free survival rates of all 52 patients were 90% (95% CI, 75-96%) and 89% (95% CI, 75-95%), respectively (Fig. 1). The estimated 5-year overall survival rates of GCB phenotype and non-GCB phenotype cases were 86% (95% CI, 63-96%) and 93% (95% CI, 59-99%), respectively, with no statistically significant difference (p=0.96). The estimated 5-year overall survival rates of the patients with and without concurrent expression of MYC and BCL2 were 100% and 88% (95% CI, 72-96%), respectively (Fig. 2). There was no significant difference between the two cohorts (p=0.74). Conclusions The results of our analysis showed good prognosis, and revealed that COO subtype and concurrent expression of MYC and BCL2 did not influence the outcome in patients with localized PG-DLBCL treated with rituximab-containing chemotherapy with or without RT. Further investigations, especially a prospective cohort study, are needed to confirm our results. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Maruyama: Eisai Co., Ltd: Honoraria. Kobayashi:Otsuka Pharmaceutical Co., Ltd.: Research Funding; ARIAD Pharmaceuticals, Inc.: Research Funding; Boehringer Ingelheim GmbH: Research Funding. Tobinai:Zenyaku Kogyo: Research Funding; Chugai Pharmaceutical: Research Funding.

Comparing Standard IPI with Revised-IPI in Patients with Diffuse Large B-Cell Lymphoma: Which Has a More Differential Potential for Predicting the Outcomes after R-CHOP Chemotherapy.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2003-2003
Author(s):  
Deok-Hwan Yang ◽  
Jae Sook Ahn ◽  
Yeo-Kyeoung Kim ◽  
Je-Jung Lee ◽  
Young Jin Choi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
B Cell ◽  
Clinical Outcomes ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Chop Chemotherapy ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract The utility of International Prognostic index (IPI) in the era of immunochemotherapy could not be determined by the available randomized trials. Recently, the study of British Columbia group suggested that a revised IPI (R-IPI) which redistributed the IPI factors into 3 distinct prognostic groups provided a more clinically useful prediction of outcome for patients with diffuse large B-cell lymphoma (DLBCL). We investigated the clinical outcomes of R-CHOP chemotherapy in patients with DLBCL for determining which has a more differential potential of predicting the prognosis among R-IPI or standard IPI. Patients and Methods: We analyzed a total of 348 patients with newly diagnosed DLBCL from National University Hospitals of Southern Korea (NUHSK) between September 2002 and July 2008. R-CHOP conducted standard doses of chemotherapy and rituximab (375 mg/m2) administered a 21-day interval. The limited-stage patients were treated with 3rd or 4th chemotherapy followed by involved field radiation therapy (IFRT) and the advanced-stage patients were treated with six to eight cycles of chemotherapy. Results: The median age was 61 years (range, 18–85) with 51.6% of patients aged above 60. After a median follow-up of 25 months (range, 2-66.8), 280 patients (80.5%) were alive and 76 patients (21.8%) had relapsed or progressed. 16 patients (4.6%) underwent autologous stem cell transplantation (ASCT). The 4-year probability of overall survival (OS) and progression-free survival (PFS) were 73.7 ± 3.4 % and 69.1 ± 3.6 %, respectively (Fig. 1A). The distribution of patients and 4-year OS rates according to IPI factors were followings; 16.7% patients had zero risk factor with 95.4%, 33.9% patients had 1 factor with 90.0%, 19.3% patients had 2 factors with 69.9%, 19.0% patients had 3 factors with 55.7%, 10.3% patients had 4 factors with 28.4% and 0.9% patients had 5 factors without reached 4-year OS rates (Fig. 1B). Both standard IPI and revised IPI showed a significant potential as prognostic variable in OS and PFS. However, the standard IPI distinguished clinical outcomes between patients with 3 risk factors and patients with 4–5 risk factors. In addition, there was no survival difference between patients with zero risk factor and patients with 1 risk factor (Fig. 2). Conclusion: The standard IPI had more differentiation potency in predicting prognosis than R-IPI in patients with DLBCL treated with R-CHOP chemotherapy. Fig. 1 Overall outcomes (A) and outcomes according to the number of IPI factors (B) Fig. 1. Overall outcomes (A) and outcomes according to the number of IPI factors (B) Fig. 2 Comparison of OS and PFS according to the standard IPI and revised IPI Fig. 2. Comparison of OS and PFS according to the standard IPI and revised IPI

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