Germinal Center B Cell and Non-Germinal Center B Cell-Like DLBCL Have Similar Clinical Features at the Time of Progression and Comparable Outcome Following Autologous HSC Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1901-1901
Author(s):  
Luciano J. Costa ◽  
Andrew L. Feldman ◽  
Ivana N. Micallef ◽  
David J. Inward ◽  
Patrick B. Johnston ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Immunohistochemical Analysis ◽  
Rank Test ◽  
First Line ◽  
First Line Therapy ◽  
Log Rank Test ◽  
Line Therapy ◽  
Germinal Center B Cell ◽  
Hsc Transplantation

Abstract Background: Germinal center B cell-like (GCB) DLBCL, as determined by gene expression profiling or immunohistochemistry, is more likely to be cured by initial conventional chemoimmunotherapy than non-germinal center B cell-like (non-GCB) DLBCL. For patients with relapsed or refractory chemosensitive DLBCL, high-dose chemotherapy and autologous hematopoietic stem cell (HSC) transplant is considered standard-of-care treatment, but it is unknown whether the outcome of these patients is similarly influenced by the subtype of DLBCL. We therefore explored the differences between patients with GCB and non-GCB DLBCL as regards their clinical features at relapse after first line therapy and their outcome following salvage autologous HSC transplant. Methods: Patients undergoing BEAM conditioning and autologous HSC transplantation for relapsed or refractory chemosensitive DLBCL at Mayo Clinic, Rochester, MN between 2001 and 2006 were included. Immunohistochemical analysis was performed for CD10, BCL-6 and MUM1 allowing classification in GCB and non-GCB-like DLBCL, as well as for BCL-2. GCB and non-GCB groups were compared in terms of known prognostic factors at time of progression and outcome after HSC transplant Results: Fifty-nine patients were included and had retrievable tumor samples to allow immunohistochemical analysis. Median follow-up of survivors was 25 months; median age at the time of transplant was 60 years (range 17–77); All patients had failed at least one previous anthracycline-based regimen (15 had refractory disease). Overall, 25/59 cases (42%) were positive for CD10, 32/58 (55%) for BCL-6, and 19/58 (32%) for MUM1. Thirty-two patients (54%) were classified as having GCB and 27 (46%) non-GCB-like DLBCL. Patients in the GCB and non-GCB group had similar time to progression (TTP) (median 12.5 months vs. 11 months, Wilcoxon P=0.81) after first line therapy and similar IPI-R scores (Chi-square, P=0.38). In univariate analysis, GCB and non-GCB did not differ in time to relapse after HSC transplant (log rank test P=0.77) or survival (log rank test P=0.48; figure). The lack of demonstrable difference in survival persisted even after correction for IPI-R and TTP, factors know to affect transplant outcome (Cox regression, RR=0.80 for GCB; P=0.28). BCL-2 was highly expressed in both GCB (81%) and non-GCB (96%) and did not correlate with outcome in the entire population nor in any of the two groups. Conclusion: Patients with chemosensitive relapsed or refractory GCB and non-GCB-like DLBCL derive similar benefit from autologous HSC transplant. Figure Figure

Differences in Cell of Origin (COO) Affect Outcomes in Caucasian(C) but Not in African American(AA) Patients with Diffuse Large B-Cell Lymphoma(DLBCL)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1460-1460 ◽  
Author(s):  
Uma Borate ◽  
Deniz Peker ◽  
James M. Foran ◽  
Luciano J Costa
Keyword(s):  
B Cell ◽  
B Cell Lymphoma ◽  
Disease Stage ◽  
Rank Test ◽  
Advanced Stage ◽  
Cell Of Origin ◽  
First Line ◽  
First Line Therapy ◽  
Log Rank Test ◽  
Line Therapy

Abstract Introduction: DLBCL is an aggressive mature B-cell neoplasm with a low incidence in African Americans and other minority groups. The differences in outcomes based on DLBCL Cell of Origin(COO) immunophenotypic subtypes as defined by the Hans algorithm using CD10, Bcl-6, and MUM1 namely germinal center B-cell (GCB) and non-GCB have been based on predominantly Caucasian patients (pts) and their impact on outcomes in AA patients have not been well studied. Material and Methods: A retrospective review of clinicopathologic data from patients diagnosed and treated for DLBCL at UAB between 2002-2011 was conducted following IRB approval .The data collected included patient demographics (age, sex, self identified race), DLBCL subtype (GCB vs. non-GCB based on the Hans algorithm), disease stage, first line therapy regimens and patient outcomes. We analyzed group differences in both C and AA pts with GCB and non-GCB subtypes of DLBCL in all the parameters mentioned above using the chi square test for categorical variables,. In addition, OS was examined using Kaplan Meier curves and the log rank test. We performed univariate and multivariate analyses to examine the effects of variables of interest on OS. All results were considered statistically significant at α=0.05 level. Results: We included a total of 259 pts in our analysis after excluding patients with missing demographics, disease related data, primary mediastianal DLBCL, missing first line therapy data and outcomes data as well as race identified as other than C or AA. 45 patients (17.4%) of patients self identified as AA and 214 (82.6%) self identified as Caucasian. The mean age of presentation for AA pts was 52 yrs compared to 58 years for C patients (p=0.045) and 28 (62.2%) AA patients presented with advanced Stage III and IV disease compared to 89 (44.6%) of C patients (P=0.04) both being statistically significant. Based on COO characterization using immunophenotype by Hans algorithm, 27 AA pts (60%) and 145(67%) of C pts were GCB by immunophenotype(p=0.317). 95% of all patients received R-CHOP as first line therapy , 3.5% received R-CVP and the remaining received a combination of Rituximab alone, FCR or radiation therapy .On analyzing OS based on COO, AA patients did not demonstrate a significant difference in OS based on COO with both GCB and non-GCB groups having a median OS of 84 months ( p=0.74)( 95% CI 72-121 months). However, the median OS for C pts with GCB phenotype was 104 months compared to 25 months for the non-GCB phenotype and the median OS was 55 months +/-12.6 months for the C pt group as a whole( p<0.001 by log rank test )which was highly statistically significant.Multivariate analyses of different factors affecting OS showed only COO (p<0.001), age(p=0.07) and stage of DLBCL at presentation(p=0.027) to affect OS significantly.Race,Gender and IPI score did not appear to impact OS significantly. Conclusion: Our study aimed to study the impact of COO and Race on OS in DLBCL especially in AA pts where this has not been well characterized. Our results show that as expected the incidence of DLBCL is lower in AA patients compared to C pts. However, DLBCL presents at younger age and with more advanced stage in AA than in C patients. Although distribution of COO is similar in AA and C patients, our findings suggest that COO may not have the same effect on prognosis among AA pts as it does among the C pt population where we see non-GCB patients do significantly worse than their GCB counterparts. This may reflect a different disease biology in AA patients that has yet to be understood. Our study limitations include not taking into account disease relapse, second line therapy and effect of autologous bone marrow transplantation on overall survival. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.

scholarly journals The first-line therapy of aggressive non-Hodgkin’s lymphomas in russian clinical practice: data from the EQUILIBRIUM study

2020 ◽  
Vol 15 (2) ◽  
pp. 10-18
Author(s):  
L. G. Babicheva ◽  
I. V. Poddubnaya
Keyword(s):  
Overall Survival ◽  
Clinical Practice ◽  
Complete Remission ◽  
B Cell ◽  
Long Term Results ◽  
First Line ◽  
Therapy Efficacy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hodgkin's Lymphomas

The objective: evaluation of effectiveness of the first-line therapy with rituximab of B-cell lymphoproliferative diseases in Russian clinical practice in the period from 2014 to 2017.Materials and methods. The EQUILIBRIUM post-registration multicenter study included 1000 patients aged 21 to 91 years old with a verified diagnosis of B-cell non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia, who received at least 4 cycles of rituximab-containing therapy with Acellbia®. The group of aggressive non-Hodgkin’s lymphomas (aNHL), which is the subject of this article, included 295 patients with a median age of 55.9 years: diffuse B-large cell lymphoma – 87 %, primary mediastinal lymphoma – 11 %, Burkitt’s lymphoma – 1 %. Group characterized by the presence of aggressive clinical signs reflecting the poor prognosis: in the majority of patients, generalized stages were diagnosed (61 %), in half of the cases (50.2 %), extranodal localization of tumor foci was detected (in 32.4 % of patients there were 2 or more). The overwhelming majority of patients (84.5 %) received adequate treatment complying with national and international recommendations (R-CHOP, R-CHOEP and R-EPOCH, high-intensity NHL-BFM-R, R-HyperCVAD and R-MACOP-B regimes). The use of R-CVP, FCR, RB, Chl-R, R-monotherapy treatment programs (which received 15.5 % of patients) was considered inadequate for this category of patients.Results. According to the results of the final assessment, high therapy efficacy was established: the overall response exceeded 90 %, complete remission was achieved in most patients with aNHL (68.5 %), partial remission – in every 5th patient (21.8 %). With a median follow-up of 15 months, 16 (5.42 %) deaths and 34 (11.53 %) events were registered. Median of event-free survival and overall survival have not been achieved. Statistically significant differences depending on first-line therapy efficacy were found in overall survival (p = 0.00000) and eventfree survival (p = 0.00000), once again confirming that the main goal of aNHL treatment is to achieve complete remission.Conclusion. Available and compliant with national clinical guidelines treatment of aNHL patients with Russian bioanalogue of anti-CD20 monoclonal antibodies (Acellbia®) demonstrates high immediate efficacy and acceptable long-term results, comparable to a retrospective analysis of previous clinical studies of the original drug rituximab.

Fludarabine Monophosphate as First Line Therapy for Chronic Lymphocytic Leukemia (CLL) - 11 Years Clinical Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4970-4970
Author(s):  
J.E. Novoa ◽  
A.L. Rojo ◽  
B. Beñaran ◽  
R. Draper ◽  
H. Calvo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Monoclonal Antibodies ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Response Rate ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Intravenous Formulation

Abstract Background: fludarabine (F) has become the standard first line therapy for chronic lymphocytic leukemia (CLL) in younger patients. Treatment of early stage patients with chlorambucil without risk stratification has not been shown to prolong survival. In recent years effective and potentially curative approaches such as nucleosides analogues, stem cell transplantation or monoclonal antibodies have been developed. The attraction of monoclonal antibodies is based on selective targeting of tumor - relevant surface markers and a distinct mechanism of action (antibody-dependent cellular cytotoxicity). Aims: to assess the efficacy, safety and quality of life of F in previously untreated B-cell CLL patients in a group of medical institutions in Uruguay during 11 years (1995–2006). Methods: 168 patients between the period 1995 – 2006 were evaluated.120 of them received F intravenous formulation (1995–2006) and 48 the oral one (2002–2006). Age: 48 – 85 years old, media 67 years old. Gender: male 90, female 78. Inclusion criteria for B-cell CLL was Binet stages B, C and A progressive (Ap), 18 to 85 years old, non multiorganic failure, performance status 0 – 2 (WHO), written informed consent. First condition was non previous treatment. Staging: Binet A 12/168, B 116/168 & C 40/168. Treatment: as first line therapy all the patients received (minimum): 6 cycles of i.v. Fludarabine (Fludara®, Schering) 25 mg/m2/daily (5 days) e/30 days or Oral Fludarabine, 40 mg/m2/daily (5 days), 6 cycles. Results: on this B-cell CLL cohort the overall response rate (ORR) was 78% (CR+PR), 80% of them have immunophenotypic response. Safety: on the 1100 cycles in 168 patients, the toxicity was: 1 AIHA, 2 pancytopenia, 3 plaquetopenia. Grade 3–4 infection rate was 1,3%. No alopecia was observed in any patient. Kaposi sarcoma (0,7%). Mortality rate: 1,7% (3/168 patients). Other adverse factors to overall survival were, age over 65 (p=0,0001) and hepatic impairment (p=0,0001). Toxicity: (WHO>2): granulocytopenia 28%, thrombocytopenia 8%, infection 2%. Although fludarabine-treated patients experienced more significant myelosuppression, no difference in the treatment group was demonstrated. Causes of death: Richter 12%, sepsis 5%, associated disease 34%, second malignancy 17% and others 30%. Comparing oral with intravenous formulation in overall survival the results were: CLL 34% vs 36% (p= NS). Conclusions: fludarabine monofosfate (Fludara®) looks like an effective and safe treatment for B-cell CLL. The oral and intravenous formulations have a similar response rate in elderly and young patients. The challenge remains to integrate new information to apply novel therapies in a disease-specific and risk-adapted maner. A longer follow up and a larger trial, might be needed to confirm these results.

CPOP-R Versus CHOP-R As First-Line Therapy for Diffuse Large B-Cell Lymphoma (DLBCL): A Phase 2, Randomized, Open-Label, Multicenter Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1605-1605
Author(s):  
Raoul Herbrecht ◽  
David MacDonald ◽  
Florian Weissinger ◽  
Martin Wilhelm ◽  
Charles Holladay ◽  
...  
Keyword(s):  
B Cell ◽  
Troponin T ◽  
Survival Rates ◽  
B Cell Lymphoma ◽  
Comparable Efficacy ◽  
High Survival ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3

Abstract Abstract 1605 Introduction: CHOP-R is standard therapy for patients with untreated DLBCL. Pixantrone dimaleate (P) is a novel aza-anthracenedione that, unlike doxorubicin (D), forms stable DNA adducts and has enhanced efficacy compared to D in preclinical lymphoma models. Due to its inability to bind iron or form alcohol metabolites, P has substantially less cardiotoxicity than D or mitoxantrone in preclinical studies. In a Phase I-II study in 65 patients with relapsed aggressive B cell NHL after CHOP (±R), patients treated with CPOP (P replaced D in CHOP) had CR/CRu rate of 52% and an overall response rate (ORR) of 77% with median progression-free survival (PFS) of 8.2 months and overall survival (OS) of 17.9 months (Leuk Lymph 2011;52: 620–8). The present Phase II study evaluated efficacy and safety, particularly cardiotoxicity, of CPOP-R vs CHOP-R as first-line therapy in patients with DLBCL. Patients and Methods: Patients with untreated DLBCL (CD20+, stage II-IV disease) were randomized to CPOP-R or CHOP-R (1: 1). CHOP-R was administered at standard doses; in CPOP-R, P (150 mg/m2) was substituted for D. After 4 cycles, patients with a partial response (PR) received 4 more cycles of treatment; those with CR received 2 more cycles. Follow-up after treatment was 36 months. Response was assessed by an independent assessment panel. A primary objective to evaluate non-inferiority of CPOP-R to CHOP-R, measured by CR/CRu rates, required 280 patients. Secondary endpoints included ORR, PFS, OS, and time to progression (TTP) and safety. Enrollment was stopped after 124 patients because of resource constraints; the study was no longer powered to detect non-inferiority. Results: Of the 124 patients enrolled, 61 were randomized to CPOP-R and 63 to CHOP-R. Treatments were administered to 122 patients (98%). Demographics and baseline disease characteristics were balanced between arms. Median age was 68 years in both arms, 79% of patients in CPOP-R vs 78% in CHOP-R were Ann Arbor stage 3–4, 48% vs 54% had IPI ≥3, and 20% vs 11% had ≥3 comorbid conditions. Median number of cycles delivered was 8 for CPOP-R vs 6 for CHOP-R. CR/CRu rate in the ITT population was 72.1% for CPOP-R vs 79.4% for CHOP-R (95% CI for the difference = −7.8%, 22.3%) and ORR (CR+CRu+PR) was 82.0% vs 87.3%. PFS appeared similar for CPOP-R and CHOP-R (HR=1.08). TTP was also similar (median not reached in either arm). Median OS was not reached in either arm (HR=2.34, 95% CI=1.05, 5.22, P =.032). The 3-year survival rates were 66% in CPOP-R vs 85% in CHOP-R. Three-year survival for patients with IPI ≤2 was 82% for CPOP-R vs 86% for CHOP-R; IPI ≥3, survival was 50% vs 84%. It was unusual that in the CHOP-R arm, patients with the modal IPI score=3 (n=25) had a better survival than patients with IPI ≤2 with only 8% mortality at 3 years. This historically high survival rate for CHOP-R patients with IPI=3 appeared responsible for the disparate survival rates between CPOP-R and CHOP-R. Eight patients in CPOP-R and 2 in CHOP-R had a history of coronary artery disease, congestive heart failure (CHF), or myocardial infarction. Overall, adverse events (AEs) were similar between arms; grade 3/4 AEs occurred in about 85% of patients in both arms. Incidence of grade 3/4 AEs was similar for neutropenia (61.0% vs 60.3%), febrile neutropenia (15.3% vs 15.9%), thrombocytopenia (5.1% vs 6.3%), and infections (16.9% vs 17.5%). Stomatitis was less common in CPOP-R (6.8% vs 17.5%). LVEF was measured prospectively at intervals through 24 months. LVEF values were generally stable in CPOP-R, but declined significantly from baseline in CHOP-R (P <.05). One patient in CPOP-R vs 8 in CHOP-R had LVEF declines ≥20% (P<.05). In CPOP-R, 6.7% of patients vs 35.2% in CHOP-R developed elevated troponin T levels (P<.05). No patients in CPOP-R vs 4 in CHOP-R developed CHF. Three deaths occurred within 30 days of last dose in CPOP-R vs none in CHOP-R. Most deaths after treatment in both arms were related to progressive disease. Conclusions: This study compared CPOP-R, a pixantrone-containing regimen, with CHOP-R as first-line therapy for DLBCL and showed comparable efficacy as measured by response, PFS, and TTP. Hematopoietic toxicities were similar; however, CPOP-R had reduced cardiotoxicity as determined by overall and serious declines in LVEF, elevations in troponin T, and CHF occurrence. Non-inferiority of CPOP-R to CHOP-R could not be established. Disclosures: Herbrecht: Cell Therapeutics, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cernohous:Cell Therapeutics, Inc: Employment. Singer:Cell Therapeutics, Inc: Employment. van der Jagt:Cell Therapeutics, Inc: Consultancy, Research Funding.

Open-label phase III randomized controlled trial comparing taxane-based chemotherapy (Tax) with lapatinib (L) or trastuzumab (T) as first-line therapy for women with HER2+ metastatic breast cancer: Interim analysis (IA) of NCIC CTG MA.31/GSK EGF 108919.

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA671-LBA671 ◽  
Author(s):  
Karen A. Gelmon ◽  
Frances Boyle ◽  
Bella Kaufman ◽  
David Huntsman ◽  
Alexey Manikhas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Rank Test ◽  
Her2 Status ◽  
P Value ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

LBA671 Background: The relative efficacy of L vs T when combined with Tax chemotherapy in the first-line setting of metastatic breast cancer (BC) is unknown. Methods: MA.31 compares Tax-based therapy, paclitaxel 80mg/m2 wkly or docetaxel 75mg/m2 3 wkly for 24 wks in combination with L or T. The L dose was 1,250 mg po daily with Tax followed by 1,500 mg daily (LTax/L). After a loading dose, the T dose was 2 mg/kg wkly or 6 mg/kg 3 wkly + Tax followed by T 6 mg/kg 3 wkly (TTax/T). Stratification was by prior neo/adjuvant HER2 therapy, prior neo/adjuvant Tax, planned Tax (paclitaxel vs docetaxel), and liver metastases. The primary endpoint is ITT progression-free survival (PFS), defined as time from randomization to objective progressive disease based on RECIST criteria or death from any cause. The protocol-specified IA was performed after observing 333 PFS events; the trial was to stop if the 2-sided p-value from the stratified log-rank test was less than 0.03. The NCIC CTG’s independent DSMC reviewed IA results and recommended disclosure because the superiority boundary was crossed. A secondary analysis utilized central laboratory-confirmed HER2 + status. Results: Between July 17 2008 and Dec 1 2011, 652 pts were accrued. Data from 636 pts (525 HER2 centrally confirmed) were included in the IA with clinical cutoff date of Nov 7 2011 and database lock of Apr 13 2012. Median follow-up was 13.6 mos, 12.9 mos for LTax/L pts and 14.0 mos for TTax/T patients. In the ITT analysis, PFS was inferior with LTax/L compared to TTax/T hazard ratio (HR) =1.33; 95% CI 1.06-1.67; p=0.01. LTax/L had median PFS 8.8 mos (95% CI 8.3-10.6) compared to TTax/T 11.4 mos (95% CI 10.8-13.7). PFS in the centrally confirmed HER2+ had HR 1.48 (95%CI 1.15-1.92; p=0.003) (LTax/L to TTax/T). No difference in overall survival was detected (LTax/L to TTax/T) HR= 1.1 (95% CI 0.75-1.61; p=0.62). More grade 3-4 diarrhea and rash was observed with LTax/L (p<0.001). Conclusions: LTax/L therapy is associated with a shorter PFS compared to TTax/T as first line therapy for HER2+ metastatic BC. ClinicalTrials.gov: NCT00667251. CCSRI grant: 021039. Supported by GlaxoSmithKline.

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