scholarly journals Venous Thromboembolic Events in Diffuse Large B Cell Lymphoma. Incidence, Risk Factors and Outcomes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3968-3968
Author(s):  
Sabarish Ayyappan ◽  
Dhivya Prabhakar ◽  
Vinita Gupta ◽  
Brenda Cooper ◽  
Hillard M. Lazarus ◽  
...  
Keyword(s):  
Risk Factors ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Patient Characteristics ◽  
Hematologic Malignancies ◽  
P Value ◽  
First Line ◽  
Bulky Disease ◽  
First Line Therapy ◽  
Line Therapy

Abstract Venous thromboembolism (VTE) is a frequent complication of hematologic malignancies, including lymphoid malignancies. VTE results in significant morbidity and mortality in lymphoma patients. There is limited information regarding the factors affecting the risk of VTE in diffuse large B cell lymphoma (DLBCL) patients treated with chemoimmunotherapy. We conducted a retrospective analysis to identify risk factors affecting the incidence of VTE and the effect of this complication on patient outcome. Methods: We searched the hematologic malignancies database of University Hospitals Seidman Cancer Center for patients newly diagnosed with DLBCL between 2004 and 2014. Records were reviewed for baseline demographics, evidence of known risk factors for VTE, disease characteristics, treatment history and baseline laboratory values. The univariate probability of overall survival (OS) and progression free survival (PFS) was estimated using the Kaplan-Meier method. The cumulative incidence procedure was used to estimate the incidence of VTE. To identify risk factors for VTE, univariate analysis was conducted on the potential risk factors for VTE and variables with P-value .25 were selected for analysis in the multivariate logistic regression model. Results: 204 patients diagnosed with DLBCL were included. Patient characteristics are presented in table 1. The median age at diagnosis was 66 years and 63% had advanced stage at diagnosis. After a median follow up was 27 months, 34 patients (16.6%) presented a VTE, with a 3-year cumulative incidence of 13.7% (95% CI 9.2-20.3%). The VTE was a pulmonary embolism in 12 subjects (35%) and deep venous thrombosis in 22 patients (65%). The diagnosis of VTE was done in the presence of active disease in 23 subjects (67%) and the first VTE occurred during the first line of chemotherapy in 16 patients (47% of VTE). Risk factors identified by univariate analysis (table 2) included previous history of VTE, coronary artery disease and congestive heart failure, bulky disease, and absence of a complete response. Treatment with an anthracycline - containing regimen resulted in decreased risk of VTE. In multivariate analysis, only the presence of bulky disease, progressive disease after first line therapy and treatment with anthracyclines retained statistical significance (p = 0.05, 0.05 and 0.006, respectively). After a median of 27 months of follow up 113 patients had presented progression after first line therapy and 72 had died. Overall, 3-year PFS was 58.6% (95% CI 51-66.2%), with lower PFS in patients experiencing VTE (3-year PFS: VTE 34.8%; no VTE 64.4%, p=0.002). 3-year OS for the whole cohort was 70.2% (95% CI 63.1-77.3%). Patients who presented VTE had a 3-year OS of 51.3% vs. 74.8% in patients without VTE (p=0.002). DLBCL patients present a high risk of VTE, with approximately half of all VTE events occurring early in the course of the disease. We were able to identify the presence of bulky disease at diagnosis and the absence of response to first line therapy as risk factors for developing VTE. The use of anthracycline-containing regimens was protective against VTE, likely because of the increased rates of disease response. Patients with VTE had worsened outcomes, likely a result of the presence of persistent disease, although a direct effect of VTE on long-term outcomes cannot be ruled out. Our results highlight the need for a heightened awareness of the increased risk of VTE in DLBCL patients and the need for prevention strategies. Table 1. Baseline patient characteristics Median age, years (range) 66 (20-92) Gender (%) Male Female 115 (56.3%) 89 (43.6%) Stage I II III IV 32 (15.9%) 43 (21.4%) 41 (20.4%) 85 (42.3%) R-IPI 0 1-2 3-5 18 (8.8%) 104 (51.0%) 80 (39.2%) Table 2. Risk Factors and results of univariate analysis Risk factor Odds Ratio p value Age > 65 1.179 0.661 Male gender 0.847 0.659 Prior congestive heart failure 5.69 0.009 Prior VTE 4.016 0.07 Increased creatinine 3.479 0.181 Morbid obesity 5.121 0.252 Prior malignancy 1.283 0.674 Bulky disease 2.425 0.035 Stage II vs. I III vs. I IV vs. I 3.742 1.343 1.906 0.058 0.703 0.338 Elevated LDH 1.329 0.450 Hemoglobin <10g/dl 0.902 0.236 Platelets < 150,000/mcl 1 0.108 Non - GCB molecular subtype 0.658 0.439 Positive FISH for t(8;14) 1.668 0.568 Anthracycline 0.383 0.050 Rituximab 5.454 0.265 Response PR vs. CR PD vs. CR SD vs. CR 0.843 0.986 0.850 0.863 1.013 1.550 Disclosures No relevant conflicts of interest to declare.

scholarly journals Valproate in combination with rituximab and CHOP as first-line therapy in diffuse large B-cell lymphoma (VALFRID)

2018 ◽  
Vol 2 (12) ◽  
pp. 1386-1392 ◽  
Author(s):  
Kristina Drott ◽  
Hans Hagberg ◽  
Karin Papworth ◽  
Thomas Relander ◽  
Mats Jerkeman
Keyword(s):  
Histone Deacetylase Inhibitor ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma ◽  
Promising Strategy ◽  
Line Therapy ◽  
Deacetylase Inhibitor ◽  
Key Points

Key Points This trial evaluates addition of the histone deacetylase inhibitor valproate to standard R-CHOP therapy in DLBCL. Addition of valproate to R-CHOP is a promising strategy in DLBCL, but auditory side effects warrant monitoring.

Rituximab Fails to Reduce Histologic Transformation (HT) Rate of Follicular Lymphoma (FL) to Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 837-837 ◽  
Author(s):  
Ariel E Marciscano ◽  
Neel Gupta ◽  
Zhigang Zhang ◽  
Julie Teruya-Feldstein ◽  
Ariela Noy
Keyword(s):  
Follicular Lymphoma ◽  
Lower Risk ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
P Value ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma

Abstract Background: Histologic Transformation (HT) of indolent follicular lymphoma to aggressive lymphoma is a critical and sometimes fatal event in a patient’s disease course. It is unclear if rituximab influences HT. We have previously shown that single agent rituximab is used earlier in the disease course than traditional chemotherapy likely due to rituximab’s high therapeutic index (Cohler et al., ASH 2007). Others have shown rituximab also improves the complete response rate, disease free and overall survival of follicular lymphoma when used as a single agent and in combination with chemotherapy. Theoretically, this could reduce the disease burden over a patient’s lifetime and consequently the transformation rate. Methods: We retrospectively screened 3500 patients and identified 584 eligible patients at Memorial Sloan Kettering Cancer Center (MSKCC) with newly diagnosed, treatment naïve, indolent follicular lymphoma. We compared two cohorts of rituximab usage: 1998– 2000 and 2001–2006. In the former, patients received rituximab predominantly in the relapsed setting. In the latter, patients liberally received rituximab even as single agent first line therapy. Histologic transformation to diffuse large B cell lymphoma (DLBCL) was the primary study endpoint. All therapy was recorded. Results: Median follow-up time was 92 months for the 1998–2000 cohort and 41 months for the 2001–2006 cohort. Patients in the latter cohort received rituximab both earlier in the course of follow up and more often as a first line therapy. The median time from diagnosis to first rituximab was 21 months vs. 2 months, respectively. Rituximab was given alone or in combination as first line systemic therapy to 36% of the 1998–2000 cohort, but to 93% of the 2001–2006 cohort. The comparative risks of transformation between the two cohorts were not statistically significant (P-value = 0.41 by log rank comparison). The cumulative incidence of transformation 36 months after diagnosis was 8.1% for the 1998– 2000 cohort and 4.4% for the 2001–2006 cohort. Furthermore, patients receiving rituximab first line, either single agent or in combination, compared to patients receiving rituximab as salvage therapy, showed essentially no difference in risk of histologic transformation. (P-value = 0.68) Surprisingly, patients never receiving rituximab had a significantly lower risk of transformation than those who received rituximab at any point (p-value = 0.0095), however, these rituximab naïve patients had lower risk FLIPI scores accounting for the difference (p-value = 0.15). Notably, 173/584 patients never received systemic therapy, and 102 of these were expectantly monitored without any local therapy, such as radiotherapy or therapeutic surgery). None of these 102 patients had transformation within the first 36-months of follow up. Finally, we confirm Ginè et al.’s earlier finding that a higher risk FLIPI score confers a higher risk of transformation. (Annals of Oncology, 2006) For each unit increase of FLIPI risk score (e.g., 3 à 4), the probability of histologic transformation at any time point increases 1.72 fold. Moreover, high-risk FLIPI patients (3–5 risk factors) have a 3.3-fold increase in risk of HT (p-value <0.0001). Conclusions: Patients diagnosed with FL in 2001–2006 received rituximab earlier in their disease and more frequently than those diagnosed in 1998–2000. However, in contrast to our hypothesis, this did not translate to a lower risk of transformation for the 2001– 2006 cohort. The 36-month risk of transformation was lower in patients with lower FLIPI scores. This data supports the clinical decision to expectantly monitor low-risk FLIPI patients.

Co-Morbidity Score at the Time of Transplant Determines Prognosis in Older Patients Who Develop Acute Graft-Vs.-Host Disease (GVHD).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2244-2244
Author(s):  
Amin M Alousi ◽  
Gabriela Rondon ◽  
Grace-Julia Okoroji ◽  
Uday Popat ◽  
Leandro De Padua Silva ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Acute Gvhd ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Older Age ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Morbidity Score ◽  
Co Morbidity

Abstract Abstract 2244 Poster Board II-221 Background: Older age patients are increasingly being considered for allogeneic hematopoietic cell transplants (HCT). Concerns related to early treatment related mortality (TRM), namely from acute GVHD, often limit referrals. Outcomes for older age patients who develop acute GVHD remain unknown. Methods: We performed a retrospective analysis of 83 adult patients enrolled onto two consecutive trials at MD Anderson to determine predictors for TRM at 6 months following systemic treatment of acute GVHD. These trials enrolled patients with newly diagnosed acute GVHD between 2000-2008 and included a single-center randomized trial of infliximab + methylprednisolone (MP) vs. MP alone and a multicenter trial of MP + one of 4 agents (mycophenolate, etanercept, denileukin diftitox or pentostatin). Results: Median age was 49 yrs (range, 20-70 yrs) and 63% of patients (pts) were male. 52% had acute leukemia and 31% were in remission at the time of transplant. Myeloablative condition and/ or peripheral blood HCT were performed in 52% and 54% of pts, respectively. Matched sibling, matched unrelated and mismatched transplants were 49%, 40% and 11%. GVHD prophylaxis was tacrolimus/ methotrexate in 87% of pts. Grades I/II, III/IV and visceral-organ acute GVHD represented 68%, 32% and 60% of pts occurring at a median time of onset of 25 days post-HCT. Day 28 acute GVHD response (defined as complete or partial response) was 63%. The median co-morbidity score at the time of HCT was 3 (range 0-11). Co-morbidity scores >3 were more common in pts >50 yrs (47%) than in those '50 yrs (24%), p=0.03. The proportion of responders on day 28 was comparable in pts >50 yrs (60%) and those '50 yrs (64%), p=0.7. On univariate analysis, significant predictors of higher TRM rate at 6 months following initiation of systemic therapy for acute GVHD were lack of response on day 28 post therapy (Hazard Ratio (HR) 3.6, p= 0.004), age > 50 yrs (HR 2.9, p=0.03) and co-morbidity score >3 (HR 3.1, p=0.01). There was no significant impact on the rate of TRM for donor type, cell source, intensity of conditioning regimen, donor/recipient sex mismatch, disease status at the time of transplant, GVHD grade at the time of initiation of systemic therapy or protocol assigned therapy. To adjust for potential interaction and confounding effects, multivariate analysis was performed by classifying pts into mutually exclusive groups according to day 28 response status, age, and co-morbidity score (see table). The cumulative incidence of TRM was lowest in pts who were '50 yrs of age and who responded to first line therapy with co-morbidity scores not impacting outcomes. TRM was comparably low (15%) in the absence of co-morbidity scores >3 in pts >50 yrs who responded to first line therapy. In contrast, in the presence of co-morbidity scores >3, TRM rate was high in pts >50 yrs regardless of whether pts responded (40%) or did not respond (100%) to first line therapy. Conclusion: The ability to withstand acute GVHD and/ or its therapy in pts older than 50 yrs depends on co-morbidity scores at the time of transplant. Disclosures: No relevant conflicts of interest to declare.

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.

Prognostic Value of 18F-FDG Positron Emission Tomography Used for Assessment of the First Line Therapy in 410 Diffuse Large B-Cell Lymphoma Patients: A Daily Practice Evaluation Before and After the Prescription of This Metabolic Imaging Technique,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3686-3686
Author(s):  
Herve Ghesquieres ◽  
Céline Ferlay ◽  
Emilie Lavergne ◽  
Emmanuelle Nicolas Virelizier ◽  
Izabela-Irina Domnisoru ◽  
...  
Keyword(s):  
Induction Therapy ◽  
B Cell Lymphoma ◽  
Daily Practice ◽  
First Line ◽  
Interim Pet ◽  
First Line Therapy ◽  
Line Therapy ◽  
Positron Emission ◽  
End Of Treatment ◽  
Initial Staging

Abstract Abstract 3686 Background: 18F-FDG Positron Emission Tomography (PET) had improved initial staging and response assessment after first line therapy of Diffuse Large B-cell Lymphoma (DLBCL). While the prognostic role of PET after induction therapy (interim PET) remains controversial, the outcome of patients with positive PET at the end of initial treatment is clearly worse as compared with negative ones. In clinical practice, many PET are performed before, during and after first line therapy for patients with DLBCL. A hypothetical effect of therapeutic decisions, guided by PET results, on DLBCL patients' outcome remained questionable. We evaluated our daily practice about PET prescription during first line therapy to explore how a complete PET could influence the DLBCL prognosis. Patients and Methods: From 1996 to 2008, 410 patients with DLBCL received first-line therapy in our institution. No selection was made on initial therapeutic intent (curative/palliative), medical history, patient's age or initial type of chemotherapy (CT) to be in accordance with daily practice setting. Study population was described and Overall Survival (OS) and Time To Progression (TTP) analysis was performed using the Kaplan Meier method. OS and TTP were compared between patients with or without PET, using the Log-Rank test. We first focused on interim PET considering patients who performed at least 3 months of the induction therapy (n=380). PET at the end of treatment were studied on patients who achieved a major part of their consolidation treatment (at least 6 months, n=354). As it was a practical study, the PET interpretation methods were not taken into account. Results: Median age at diagnosis was 65 years (range: 19–97). Most patients received CHOP-like CT (53%) or high-dose CHOP CT (31%). Rituximab was associated to CT for 269 patients (66%). PET was performed at initial staging, after induction therapy and at the end of initial treatment respectively on 77, 72 and 94 patients. We first observed that patients who had a pre-treatment PET presented a significantly higher rate of III-IV Ann Arbor stage than patients evaluated by conventional methods (71% vs. 57%, p =.021). Patients who had an interim PET were younger (median age: 55 vs. 67 years, p <.001), presented a higher age-adjusted IPI score (2–3, 66% vs. 47%, p =.004) and were more frequently treated by rituximab (96% vs. 61%, p <.001) than patients who did not have a PET, that is in accordance with the date of approval of rituximab for DLBCL in 2002. The same observation was done for patients who had a PET at the end of the treatment. No difference in TTP was observed between patients who had an interim PET and patients evaluated by conventional methods (p =.543), with 5-year TTP rates of 65.6% (CI95% [51.0–76.8]) and 70.3% (CI95% [64.5–75.3]) respectively. Similarly, no difference in OS was observed between these groups. Neither OS nor TTP were found to be statistically different between patients evaluated at the end of treatment with a 5-year TTP rates of 72.4% (CI95% [61.5–80.7]) for patients who performed a TEP at the end of the treatment and 73.8% (CI95% [67.6–78.9]) (p =.653) for the others. Preliminary results showed a worse prognosis for patients who had a positive PET at completion of first line therapy with a 5-year OS rate of 50.0% (CI95% [22.9–72.2]) compared with 84.4% (CI95% [70.4–92.1]) for patients with negative PET (p =. 001). However, no observe a prognostic value of positivity of interim PET performed at mid-treatment was observed. Conclusions: Results of this retrospective clinical practice study are consistent with the usefulness of PET for initial staging of DLBCL patients and a poor prognosis of positive PET at the end of first line therapy. Using PET for evaluation of treatment response after induction therapy or after treatment completion was not found to be significantly associated with patient's prognosis. Modification of therapeutic decision based on PET results need to be more accurately explored with a prospective clinical trial. Disclosures: No relevant conflicts of interest to declare.

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.

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.

Sign in / Sign up

Export Citation Format

Share Document