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.

scholarly journals Relapses after Achieving EFS24 in Patients with Diffuse Large B-Cell Lymphoma in the Rituximab Era

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 454-454 ◽  
Author(s):  
Yucai Wang ◽  
Umar Farooq ◽  
Brian K. Link ◽  
Mehrdad Hefazi ◽  
Cristine Allmer ◽  
...  
Keyword(s):  
B Cell ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
Newly Diagnosed ◽  
Indolent Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: The addition of Rituximab to chemotherapy has significantly improved the outcome of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Patients treated with immunochemotherapy for DLBCL who achieve EFS24 (event-free for 2 years after diagnosis) have an overall survival equivalent to that of the age- and sex-matched general population. Relapses after achieving EFS24 have been considered to be unusual but have been understudied. We sought to define the rate, clinical characteristics, treatment pattern, and outcomes of such relapses. Methods: 1448 patients with newly diagnosed DLBCL from March 2002 to June 2015 were included. Patients were enrolled in the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma SPORE, treated per physician choice (predominantly R-CHOP immunochemotherapy) and followed prospectively. An event was defined as progression or relapse, unplanned re-treatment after initial therapy, or death from any cause. Cumulative incidence of relapse and non-relapse mortality after achieving EFS24 were analyzed as competing events using Gray's test in the EZR software. Post-relapse survival was defined as time from relapse to death from any cause and analyzed using Kaplan-Meier method in SPSS (V22). Results: Among the 1448 patients, 1260 (87%) had DLBCL alone at diagnosis, and 188 (13%) had concurrent indolent lymphoma (follicular lymphoma 115, marginal zone lymphoma 18, chronic lymphocytic leukemia 14, lymphoplasmacytic lymphoma 4, unspecified 37) at diagnosis. After a median follow-up of 83.9 months, 896 patients achieved EFS24. For all 896 patients who achieved EFS24, the cumulative incidence of relapse (CIR) was 5.7%, 9.3% and 13.2%, respectively, at 2, 5 and 10 years after achieving EFS24. Patients with concurrent indolent lymphoma at diagnosis had a higher CIR compared to those with DLBCL alone at diagnosis (10.2 vs 4.8% at 2 years, 15.7 vs 8.0% at 5 years, 28.8 vs 9.7% at 10 years, P<0.001; Figure 1). There were a total of 84 patients who relapsed after achieving EFS24. The median age at initial diagnosis was 66 years (range 35-92), and 48 (57%) were male. At diagnosis, 11 (13%) had ECOG PS >1, 37 (50%) had LDH elevation, 62 (74%) were stage III-IV, 14 (17%) had more than 1 extranodal site, and 26 (31%) were poor risk by R-IPI score. There were 58 patients with DLBCL alone at diagnosis who relapsed after achieving EFS24, and 38 (75%) relapsed with DLBCL, 13 (25%) relapsed with indolent lymphoma (predominantly follicular lymphoma), and pathology was unknown in 7 patients. In contrast, there were 26 patients with concurrent indolent lymphoma at diagnosis who relapsed after achieving EFS24, and 9 (41%) relapsed with DLBCL, 13 (59%) relapsed with indolent lymphoma, and pathology was unknown in 4 patients. In the 47 patients who relapsed with DLBCL after achieving EFS24, 45% received intensive salvage chemotherapy, 19% received regular intensity chemotherapy, 9% received CNS directed chemotherapy, and 36% went on to receive autologous stem cell transplant (ASCT). In the 26 patients who relapsed with indolent lymphoma after achieving EFS24, 27% were initially observed, 54% received regular intensity chemotherapy, 4% received intensive salvage chemotherapy, and 19% received ASCT after subsequent progression. The median post-relapse survival (PRS) for all patients with a relapse after achieving EFS24 was 38.0 months (95% CI 27.5-48.5). The median PRS for patients who relapsed with DLBCL and indolent lymphoma after achieving EFS24 were 29.9 (19.9-39.9) and 89.9 (NR-NR) months, respectively (P=0.002; Figure 2). Conclusions: Relapses after achieving EFS24 in patients with DLBCL were uncommon in the rituximab era. Patient with DLBCL alone at diagnosis can relapse with either DLBCL or indolent lymphoma (3:1 ratio). Patients with concurrent DLBCL and indolent lymphoma at diagnosis had a significantly higher CIR, and relapses with DLBCL and indolent lymphoma were similar (2:3 ratio). Even with high intensity salvage chemotherapy and consolidative ASCT, patients who relapsed with DLBCL had a significantly worse survival compared to those who relapsed with indolent lymphoma. Late relapses with DLBCL remain clinically challenging, with a median survival of 2.5 years after relapse. Figure 1. Figure 1. Disclosures Maurer: Celgene: Research Funding; Nanostring: Research Funding; Morphosys: Research Funding. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ansell:Takeda: Research Funding; Pfizer: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Celldex: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Merck & Co: Research Funding; Bristol-Myers Squibb: Research Funding. Cerhan:Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding.

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 Prognostic Impact of Gastrointestinal Involvement in Newly Diagnosed Diffuse Large B-Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5400-5400
Author(s):  
David Kasouha ◽  
Nicola Lehners ◽  
Katharina Kriegsmann ◽  
Gerlinde Egerer ◽  
Anthony D Ho ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Elevated Serum ◽  
B Cell Lymphoma ◽  
Treatment Modalities ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Curative Intent ◽  
Large B Cell Lymphoma

Abstract Introduction: Involvement of >1 extranodal site is regarded as a poor prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). It is necessary to clarify the prognostic impact of specific extranodal sites. Gastrointestinal (GI) involvement is one of the most frequently involved extranodal sites. Methods: Patients with newly diagnosed DLBCL treated at the University of Heidelberg between 06/2001 and 07/2015 were identified and included in this retrospective analysis. Data on clinical characteristics and treatment modalities were obtained by review of medical charts. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The impact of variables on PFS and OS was evaluated by univariate log-rank tests and by multivariate analysis using the Cox proportional hazards model. Results: A total of 1001 patients were identified of whom 119 (11.9%) presented with GI involvement. Median age of patients with GI involvement was 63.3 years [range 19.1-86.7], 71 (59.7%) were male. 92 patients had an available international prognostic index (IPI) score, 36 (39.1%) IPI 0-1, 33 (35.9%) IPI 2-3, and 23 (25%) IPI 4-5. The most frequently involved organs of GI were stomach (51.3%), small intestine (39.5%), colon (20.2%), and esophagus (2.5%). 107 (89.9%) patients were treated in curative intent and were further analyzed regarding the prognostic impact of several factors on outcome. 80.4% of them received CHOP-like therapies, 17.8% received chemotherapy more aggressive than CHOP, typically addition of etoposide or treatment with high-dose methotrexate in case of CNS involvement, 87.9% received additional rituximab, and 22.4% additional radiotherapy In DLBCL patients with GI involvement, we identified factors associated with worse OS (P<.05) by univariate analysis: B symptoms, elevated serum LDH, and involvement of more than two extranodal sites. On the contrary, age (>60 years), sex, Ann Arbor Stage (AAS) III/IV, and Performance Status of Eastern Cooperative Oncology Group (ECOG) more than one, and elevated serum sCD25 did not have any significant impact on OS. B symptoms were as well associated with decreased PFS (P<.05) by univariate analysis. Multivariate Cox Regression analysis revealed that patients with elevated serum LDH at diagnosis had significantly worse OS (P<.05), and patients with B symptoms had significantly worse PFS (P<.05). Regarding first-line treatment modalities, escalation of chemotherapy to more aggressive regimes than CHOP was associated with a prolonged OS and PFS in univariate analysis, not in multivariate analysis. Radiotherapy did not have any significant impact on OS or PFS. Regarding all DLBCL patients treated with curative intent, GI involvement did not have any significant prognostic impact on OS or PFS. Conclusions: In this retrospective registry analysis of patients with newly diagnosed DLBCL with GI involvement, B symptoms, elevated serum LDH, and involvement of more than two extranodal sites were identified as risk factors for inferior OS. Escalation of chemotherapy to more aggressive regimes than CHOP was associated with a prolonged OS and PFS. Further analyses are required as toward which treatment modalities might be best suited to improve prognosis of GI involvement. Disclosures Kriegsmann: Celgene: Research Funding; BMS: Research Funding.

The Outcome of Primary Mediastinal Large B-Cell Lymphoma (PMBCL) in the R-CHOP Treatment Era

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 303-303 ◽  
Author(s):  
Kerry J. Savage ◽  
Paul R. Yenson ◽  
Tamara Shenkier ◽  
Richard Klasa ◽  
Diego Villa ◽  
...  
Keyword(s):  
B Cell ◽  
Fdg Pet ◽  
Research Funding ◽  
Who Classification ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Pet Scan ◽  
Chop Chemotherapy ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 303 Background: Primary mediastinal large B-cell lymphoma (PMBCL) was distinguished from DLBCL in the REAL/WHO classification by virtue of distinct clinical and pathologic features. In DLBCL, R-CHOP has demonstrated a clear benefit over CHOP chemotherapy in randomized trials, some of which have included a small subset of PMBCL pts (pts). However, large studies evaluating R-CHOP in PMBCL are lacking. Further, the role of consolidative radiotherapy (RT) to the mediastinum remains unclear particularly with the more frequent use of FDG-PET. At the BCCA, from 2001–2005, R-CHOP with consolidative RT was recommended in all pts with PMBCL. After 2005, FDG-PET scan was used to guide RT usage following 6 cycles of R-CHOP. We evaluated: 1) the outcome of pts with PMBCL in R-CHOP vsCHOP treated pts; 2) prognostic factors in R-CHOP treated pts; 3) the impact of the introduction of PET based approach to guide RT compared to the use routine RT. Methods: Using the BC Cancer Agency Centre for Lymphoid Cancer database, we identified all pts with PMBCL by the REAL/WHO classification treated with R-CHOP in addition to an earlier group treated with CHOP chemotherapy. For R-CHOP treated pts, from 2001–2005, consolidative RT to the mediastinumwas routinely administered following R-CHOP (‘RT’ era). Since 2005, a PET was planned at the end of chemotherapy to guide RT (‘PET’ era). If the PET was negative, pts were observed and if the PET was positive, consolidative RT was given, if feasible. Results: In total, 176 pts were identified: 96 received R-CHOP; 80 received CHOP. Baseline clinical features were similar between the treatment groups. Compared to those treated with CHOP, R-CHOP pts had an improved time to progression (TTP) (5 y 78% vs 65%, p=0.018) and overall survival (OS) (5 y 88% vs 70%, p=0.015). Further, refractory disease (progressive disease (PD) on chemotherapy or relapse < 3 months after treatment completion) was more frequent in CHOP treated pts (16% vs 5%, p=0.016). There was no difference in the risk of central nervous system (CNS) relapse (3.2% vs2.1%, p=0.823). For the R-CHOP treated pts, 46 were treated in the ‘RT era’; 80% received consolidative RT; 50 were treated in the ‘PET era’; 38% received RT. In the RT era, there was a greater proportion of pts with extranodal sites > 1 (p=0.007) and the presence of a pleural/pericardial effusion (p=0.009). In an era to era outcome comparison, there was no difference in the 5 y TTP (RT era 76% vs PET era 83%, p=0.626) or 5 y OS (82% vs 89%, p=0.773). In univariate analysis, the presence of B symptoms was associated with an inferior TTP (5 y 67% vs 90%, p=0.014) and OS (5 y 83% vs 94%, p=0.047). An effusion at diagnosis was associated with an inferior TTP (p=0.017) but not OS (p=0.277). Using recursive partitioning, age > 38 y was identified as the optimal cut-off and was associated with an inferior OS (p=0.003) and there was a trend to a worse TTP (p=0.096). The aaIPI was not predictive of TTP (p=0.357) or OS (p=0.386). In multivariate analysis (including variables with p value<.1 and treatment era), B symptoms (HR 4.3 p=0.011), an effusion (HR 2.97, p=0.025) and age > 38 y (HR 2.98, p=0.025) were associated with an inferior TTP. For OS, age > 38 y (HR 6.7, p=0.003) and B symptoms (HR 4.5, p=0.023) were associated with an inferior outcome. Treatment era (RT vsPET) did not affect TTP or OS in MVA. In total, 59 pts treated with R-CHOP had a PET scan at the end of treatment, 50 in the PET era and 9 pts in the ‘RT era’ by self-pay: 35 (59%) were PET-negative (neg) (2 received RT) and 24(41%) were PET-positive (pos) (23 received RT). With a median follow-up of 5.4 y, there was no difference in the TTP (5 y 78% vs 83%, p=0.735) or OS (5 y 88.5% vs 95%, 0.271) for PET-neg and PET-pos cases, respectively. In total, there were 6 relapses in PET-neg cases: 2 CNS and 4 mediastinal. There were 4 relapses in the PET pos cases (PD in the mediastinum at PET scan n=1; within in RT field n=1; within and outside RT field n=1; outside RT field n=1). Conclusion: We confirm the superior outcome using R-CHOP compared to CHOP chemotherapy in PMBCL, however, rituximab does not appear to impact the rare risk of CNS relapse. The introduction of a PET-guided RT approach in R-CHOP treated PMBCL pts has maintained excellent outcomes in the majority of pts while reducing the use of RT. The presence of B symptoms at diagnosis was associated with an increased risk of relapse and may reflect more aggressive underlying disease biology. Disclosures: Savage: Roche: Research Funding. Klasa:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Villa:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Slack:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Gascoyne:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Connors:Roche: Research Funding. Sehn:F. Hoffmann-La Roche (Roche Canada): Research Funding.

Lymphocyte Count Persistence and Early Recovery Predicts Superior Survival and Is Independent of the International Prognostic Index in Patients Treated with CHOP Chemotherapy for Diffuse Large B Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3252-3252 ◽  
Author(s):  
Luis F. Porrata ◽  
Kay M. Ristow ◽  
Svetomir N. Markovic ◽  
Daniel Persky ◽  
Thomas M. Habermann
Keyword(s):  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Chop Chemotherapy ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract The peripheral blood absolute lymphocyte count (ALC) post-autologous stem cell transplantation is an independent predictor for survival in non-Hodgkin’s lymphoma. The role of ALC recovery during and after standard CHOP chemotherapy for newly diagnosed diffuse large B cell lymphoma (DLBCL) has not been reported. We hypothesized that ALC recovery during/after CHOP chemotherapy has a direct impact on survival. 135 consecutive newly diagnosed patients with DLBCL treated with CHOP from 1994 through 2000 were retrospectively analyzed. The primary end point was to assess the role of ALC recovery during and after CHOP on progression-free survival (PFS) and overall survival (OS). The ALC recovery before each of the 6 cycles and at 3 months follow-up after completion of therapy were analyzed. Of the 135 patients, 41 patients received concomitant radiation therapy. The median age was 64 years (range: 21–83) and median follow-up was 46 months (range: 1–124). Superior OS and PFS were identified in patients achieving the ALC cut-off value that discriminated clinical outcomes at a high level of significance for blood counts obtained before cycles 1 (ALC ≥ 1.5 x 109/L, OS = not reached vs 54 months, p< 0.0048; PFS = not reached vs 23 months, p <0.0005), 2 (ALC ≥1.5 x 109/L, OS = not reached vs 59 months, p <0.0255; PFS = not reached vs 30 months, p <0.0082), 3(ALC ≥1.2 x 109/L, OS = not reached vs 59 months, p<0.0074; not reached vs 30 months, p <0.0060), and at 3 months (ALC ≥ 1.2 x 109/L, OS = not reached vs 60 months, p< 0.0080; PFS = not reached vs 42 months, p < 0.0017). Similar cut-off points for cycles 4 through 6 could not be identified. The ALC recovery between each cycles 1–3 and at 3 months were not independent of each other. Multivariate analysis demonstrated ALC for cycles 1–3 and at 3 months post CHOP to be independent prognostic factor for OS and PFS when compared to other significant prognostic factors including International Prognostic Index and radiation therapy. Patients were stratified into three groups based on whether or not they achieved cut-off values of ALC in the first 3 cycles: group I= ALC achieved in at least 2 of 3 cycles; group II= ALC achieved in only 1/3 cycles; and group III= ALC cut-off not achieved. A trend towards worse OS (p< 0.0035) (Figure 1) and PFS (p< 0.0003) was identified if patients did not achieve any of the cut-off values of ALC in the first 3 cycles. These data further support the hypothesis that there is a critical role of lymphocyte (immune) recovery during and after CHOP chemotherapy in DLBCL.

Rituximab-CHOP Versus CHOP Alone in Patients with Diffuse Large B Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4708-4708
Author(s):  
Mustafa Cetiner ◽  
Taflan Salepci ◽  
Elif Birtas Atesoglu ◽  
Mahmut Gumus ◽  
Aslihan Guven ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Chop Chemotherapy ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell ◽  
Chop Therapy

Abstract Recently, the cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen plus rituximab (R-CHOP) have been used widely to treat patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) and it has also been reported to improve the outcome of DLBCL. We represent a retrospective analysis of newly diagnosed DLBCL patients between the years of 2003–2005 to evaluate the impact of R-CHOP therapy on response rates. Patients with DLBCL between 20–80 years of age (median: 46.0 and mean 56.2 ± 14.92) received 6 cycles of R-CHOP (n=28). For comparison, DLBCL patients between 15–76 years of age (median: 60.5 and mean 47.3 ± 16.6) who received 6 courses of CHOP therapy (n=30) were used as the control group. All patients received classical CHOP (cyclophosphamide 750 mg/m m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m m2 on day 1 and prednisone 40 mg/m m2 for 5 days) every 4 weeks. In R-CHOP group, rituximab 375 mg/m m2 was administered one day before CHOP chemotherapy. The median follow-up for R-CHOP and CHOP groups were 15.66 ± 5.90 (7–29) and 21.79 ± 9.20 (8–46) months, respectively. The International Prognostic Index (IPI) scores were not significantly different between these groups (median IPI of R-CHOP: 2.0 and mean IPI 2.01.27 ± 1.16 versus median IPI of CHOP: 1.0 and mean IPI 1.88 ± 1.26). Complete response (CR) and complete undetermined response (CuR) rate for R-CHOP was 92% (26 of 28 patients) which was statistically significantly higher than CHOP (24 of 30 patients, 80%) (p=0.004). Partial response (PR) rates for R-CHOP and CHOP groups were 7% (2 of 28 patients) and 10% (3 of 30 patients), respectively. While there were no unresponsive patients in the R-CHOP group, refractory disease rate was 10% (3 of 30 patients) in the CHOP group. Relapse rates during the follow up period were 13% (4 of 30 patients) for CHOP and 4% (1 of 28 patients) for R-CHOP group (p&lt;.0001). No long-term toxicity appeared to be associated with the addition of rituximab to the CHOP combination. These results also confirmed the benefit of the addition of rituximab to standard CHOP chemotherapy in DLBCL even in young patients with low IPI scores.

Use of Rituximab with CHOP Chemotherapy Appears to Overcome Racial Disparities In Survival In Black Patients with Diffuse Large B Cell Lymphoma When Compared to CHOP Chemotherapy Alone.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1528-1528
Author(s):  
Uma Borate ◽  
Pareen J Shenoy ◽  
Will Donnellan ◽  
Kevin Bumpers ◽  
Tanyanika Douglas-Holland ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Chop Chemotherapy ◽  
Multivariate Models ◽  
Large B Cell Lymphoma ◽  
Black Patients ◽  
Younger Age ◽  
Male Sex ◽  
Large B Cell

Abstract Abstract 1528 Background: While black patients (pts) have a lower relative incidence of Diffuse Large B cell lymphoma (DLBCL),previous studies have shown that they tend to present at a younger age, with more advanced stage disease and have inferior 2 year and 5 year relative survival rates (ASH 2007 4430a; ASH 2009 898a). These studies have been limited by small numbers of black pts and by being single institution analyses. We performed a combined retrospective analysis of DLBCL pts treated at Emory & University of Alabama at Birmingham (UAB) to examine demographic, clinical, International Prognostic Index (IPI) score, socioeconomic, and treatment variables to determine their impact on survival in black (B) and white (W) pts. Methods: Clinical, pathology, and pharmacy records were reviewed and 862 pts were identified with DLBCL who were evaluated or received treatment at Emory and UAB from 1981–2010. Baseline demographic data, components of the IPI [age, stage, performance status (PS), LDH, number of extranodal sites (ES)], family history of lymphoma, insurance & employment status, as well as treatment and survival data were extracted. Pts with incomplete treatment and outcomes data or unknown race were excluded (n=87) as were n=157 who received treatments other than CHOP or R-CHOP. The primary outcome was overall survival (OS). Differences in baseline features and treatment category were analyzed using Chi-squared statistical analysis. Univariate & multivariate logistic regression analyses were performed for the entire population and cohorts matched by IPI, age, year of diagnosis and socioeconomic factors, to determine predictors of 2-year and 5-year survival. Results: A total of 618 pts with DLBCL (n=484 W, n=134 B) who received either CHOP (n=249) or R-CHOP (n=369) were included in the present analysis. Univariate analyses demonstrated that age >60 yrs, PS 32, ES32, presence of B symptoms, high LDH, and IPI score 32 but not race were each significantly associated with a poorer survival. In multivariate Cox analysis age >60 (Hazard Ratio (HR) 1.5, 95%CI 1.2–2.9), PS 32 (HR 2.6, 95%CI 2.0–3.5), and male sex (HR 1.2, 95%CI 1.0–1.5) (p=0.047) predicted significantly worse survival. Treatment with R-CHOP was associated with significantly better survival (HR 0.6, 95%CI 0.4–0.9). In multivariate models of pts treated with CHOP, white race was associated with significantly better survival (HR 0.6, 95%CI 0.4–0.9) (see Figure) while IPI scores 3–5 (HR 3.1, 95%CI 1.9–4.9) and male sex (HR 1.5, 95%CI 1.0–2.1) were associated with worse survival. However among pts treated with R-CHOP, IPI scores 3–5 (HR 3.2, 95%CI 1.8–5.7) and Medicaid insurance (HR 2.8, 95%CI 1.4–5.5) but not race or gender was associated with worse survival. In multivariate models of pts treated with CHOP, white race was associated with better survival (HR 0.6, 95% CI 0.4–0.9) while IPI scores 3–5 (HR3.1, 95% CI 1.9–4.9) and male sex (HR1.5, 95%CI 1.0–2.1) were associated with worse survival. Univariate & multivariate analysis of 2-yr OS and 5-yr OS also demonstrated that IPI scores 3–5, and all IPI components individually were associated with significantly worse survival. In both univariate and multivariate analysis, treatment with R-CHOP was associated with significantly better 2-yr (OR 2.9, 95%CI 1.8–4.6) and 5-yr OS (OR 1.8, 95%CI 1.2–2.9) irrespective of race or insurance status. Conclusion: Previous studies looking at racial differences in treatment of DLBCL showed that black pts present at a younger age,with more advanced disease and were less likely to be treated with combined immunochemotherapy. Our combined institutional study with a large cohort of black pts with DLBCL and detailed ascertainment of prognostic factors and therapy showed that treatment with CHOP is significantly associated with inferior survival in black pts. However, treatment with R-CHOP appears to overcome race as a prognostic factor and is associated with significantly improved survival in all pts subgroups irrespective of race and disease status. This suggests that potential biological differences in DLBCL biology may exist between W & B pts that are no longer prognostic with the addition of rituximab, which we are further exploring with DLBCL subtyping and a study of candidate single nucleotide polymorphisms. Disclosures: Flowers: Genentech/Biogen-Idec (unpaid): Consultancy; Celgene, Intellikine: Consultancy; Millennium: Research Funding. Foran:GlaxoSmithKline: Research Funding.

scholarly journals Evaluation of the Prognostic Utility of Bone Marrow Biopsy in Diffuse Large B-Cell Lymphoma: A SEER-Medicare Linked Database Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Danny Luan ◽  
Yiyuan Wu ◽  
Jordan S. Goldstein ◽  
Sarah C. Rutherford ◽  
John P. Leonard ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Temporal Trends ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
First Line ◽  
Large B Cell Lymphoma ◽  
Pet Ct

Background: Positron emission tomography-computed tomography (PET-CT) has become the primary modality for initial staging in diffuse large B-cell lymphoma (DLBCL) [Barrington et al, J Clin Oncol 2014; Cheson et al, J Clin Oncol 2014]. Recently, the role of a staging bone marrow biopsy (BMB) has become less clear. A meta-analysis suggested that PET-CT can miss bone marrow involvement [Adams et al, Eur J Nucl Med Mol Imaging 2014], but recent guidelines on staging suggested that BMB should be optional. We analyzed temporal trends in use of different screening modalities and evaluated the association between patient outcomes and staging modality (PET-CT with BMB compared to either PET-CT without BMB or CT with BMB) in patients with DLBCL in SEER-Medicare. We hypothesized that use of PET-CT as screening would increase over time and that use of BMB would decrease over time. We also hypothesized that use of BMB would not be associated with an improvement in overall survival in patients staged with PET-CT. Methods: 70,858 patients diagnosed with DLBCL in SEER-Medicare were identified with ICD-O-3 SEER histology codes 9680 and 9684. In this analysis, we included 7,159 patients who were diagnosed between 2002 and 2015, were treated with first-line rituximab, cyclophosphamide, vincristine, and doxorubicin chemotherapy regimens, and had claims for PET-CT and/or BMB within 30 days on either side of diagnosis. The patients were divided into screening categories of patients receiving PET-CT without BMB (PET-CT w/o BMB), patients receiving BMB with CT (i.e., no PET-CT) (CT w/ BMB), and patients receiving both screening modalities (PET-CT w/ BMB). Overall survival (OS) was calculated from date of diagnosis to death. Kaplan-Meier (KM) curves were used to estimate survival probabilities across screening categories and log-rank tests (LRT) were used to statistically evaluate differences between OS curves. Cox proportional hazards (CoxPH) models were used to estimate hazard ratios prior to and following adjustment for confounders. Results: 2,059 patients received PET-CT w/o BMB, 1,539 received CT w/ BMB, and 3,561 received PET-CT w/ BMB. Proportions of patients receiving PET-CT w/ BMB and PET-CT w/o BMB increased across years of diagnosis (36.7 to 51.9% and 17.4 to 36.1%, respectively, between 2002-2005 and 2013-2015), while the proportion of patients receiving CT w/ BMB decreased across years of diagnosis (45.8 to 12.0%) (Table 1). Similarly, the proportion of patients receiving BMB independent of imaging modality also decreased (28.8% to 16.8%). In bivariate analyses, categories of screening were significantly associated with age category, sex, year of diagnosis, race, stage, nodal status, poor performance status, Charlson Comorbidity Index (CCI), number of first-line cycles, and geographic classification, with receipt of PET-CT w/ BMB being more common in patients who are younger, male, diagnosed in later years in urban settings, and received &gt;4 first-line cycles, with earlier stage at diagnosis, nodal disease, good performance status, and lower CCI (Table 1). In unadjusted KM analysis, median survival among patients receiving PET-CT w/ BMB was 8.7 years, compared to 8.1 and 7.6 years among patients receiving PET-CT w/o BMB and CT w/ BMB, respectively (LRT P&lt;0.0001; Figure 1). In fully adjusted CoxPH models, patients receiving PET-CT w/ BMB did not have a significantly better OS compared to those receiving PET-CT w/o BMB (HR: 0.93; 95% CI, 0.84-1.02; P=0.1075). Separately, patients receiving CT w/ BMB had a significantly worse OS compared to those receiving PET-CT w/o BMB (HR: 1.13; 95% CI, 1.02-1.26; P=0.0212), even though OS was not significantly associated with year of diagnosis (P=0.6613). Conclusions: In this SEER-Medicare cohort of 7,159 patients with newly diagnosed DLBCL, we found temporal trends supporting increased use of pretreatment staging PET-CT and decreased use of BMB. We also found that use of PET-CT w/ BMB did not provide a survival benefit as compared to use of PET-CT w/o BMB. These data would suggest that use of BMB could be spared in patients newly diagnosed with DLBCL over the age of 65, unless otherwise clinically indicated. Interestingly, the finding of no OS benefit across years of diagnosis suggests that improvements in outcomes in recent trials may be due to patient selection. Given the limitations associated with registry data, the study warrants replication in more complete DLBCL data sets. Disclosures Rutherford: Genentech/Roche: Research Funding; Karyopharm: Consultancy, Research Funding; Regeneron: Research Funding; Celgene: Consultancy; Kite: Consultancy; Dova: Consultancy; Seattle Genetics: Consultancy; AstraZeneca: Consultancy; LAM Therapeutics: Research Funding; Heron: Consultancy; Juno: Consultancy. Leonard:Miltenyi: Consultancy; Karyopharm: Consultancy; Gilead/Kite: Consultancy; Sutro: Consultancy; Bayer: Consultancy; BMS/Celgene: Consultancy; MEI Pharma: Consultancy; Epizyme: Consultancy; Roche/Genentech: Consultancy; Regeneron: Consultancy; ADC Therapeutics: Consultancy; GenMab: Consultancy; AstraZeneca: Consultancy. Martin:Kite: Consultancy; Morphosys: Consultancy; Regeneron: Consultancy; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Bayer: Consultancy; Incyte: Consultancy; Cellectar: Consultancy; Beigene: Consultancy; Celgene: Consultancy; Teneobio: Consultancy.

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