Survival Benefits of Patients with Non-Hodgkin’s Lymphoma Treated with Rituximab Combined with Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4625-4625
Author(s):  
Zhixiang Shen ◽  
Junmin Li ◽  
Aihua Wang ◽  
Yu Chen

Abstract Purpose: Rituximab combined with chemotherapy has been recommended as first-line or second-line standard regimen in most subtypes of B-cell lymphoma in China by the 2004 National Comprehensive Cancer Network lymphoma therapy guideline. We have conducted a multicenter trial to evaluate the efficacy and safety of rituximab in combination with standard chemotherapy (CHOP) in patients with previously untreated or relapsed indolent and aggressive NHL. Methods: Patients received 4–8 cycles of rituximab plus CHOP every 21 days. For each cycle, rituximab (375mg/m2) was given on day 1 and CHOP started on day 3. CHOP consisted of cyclophosphamide 750mg/m2, doxorubicin 50mg/m2, and vincristine 1.4mg/m2 (maximum 2mg/dose) given intravenously on day 3, and oral prednisone 100mg on days 3–7. Results: A total of 221 patients were enrolled on the trial, 128 males and 93 females with a mean age of 49 years (range 10–83 years). The main lymphoma subtypes were small lymphocytic (15 patients, 7%), follicular (27 patients, 12%), and diffuse large B-cell (160 patients, 72%). In total, 56 patients had indolent NHL and 165 aggressive NHL. The overall response rate for all patients was 86% with 57% complete responses. In patients with indolent NHL the overall and complete response rates were 95% and 55% respectively. After a median 12 months follow up, progression-free survival in patients with indolent NHL was 88%±5% at 1 year and 83%±6% at 2 years. In the 160 patients with diffuse large B-cell lymphoma, the overall response rate was 88% with 61% complete responses, and after a mean follow-up of 6 months, predicted 1-year and 2-year progression-free survival were 88%±5% and 83%±7% respectively. Infusion-related adverse events occurred in 4% of patients, associated with the first infusion of rituximab. Subanalyses according to subtype, stage, IPI and other factors will be presented. Conclusion: Rituximab plus chemotherapy is an effective, well-tolerated treatment that achieves high response rates and long progression-free survival in both indolent and aggressive NHL.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8502-8502 ◽  
Author(s):  
Anas Younes ◽  
Ian Flinn ◽  
Jesus G. Berdeja ◽  
Jonathan W. Friedberg ◽  
Sara Alberti ◽  
...  

8502 Background: Ibrutinib, a first-in-class oral Bruton’s tyrosine kinase inhibitor, has demonstrated single-agent activity in a variety of relapsed or refractory B-cell malignancies with limited toxicity, making it an appropriate drug to combine with standard R-CHOP chemotherapy in patients with previously untreated NHL. Methods: Patients received oral daily dose of ibrutinib (280, 420, or 560 mg) in combination with standard doses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, and vincristine on day 1, and prednisone on days 1 through 5 of each 21-day cycle for up to 6 cycles). The primary objective was to determine the recommended phase 2 dose (RP2D) of ibrutinib in combination with standard R-CHOP (IR-CHOP). The secondary objectives were to assess safety, overall response rate, pharmacokinetics, and pharmacodynamic biomarkers. Results: Seventeen patients (7, 4, and 6 in increasing ibrutinib doses) were enrolled: 59% male, median age 65 (range 46-81) years, diffuse large B-cell lymphoma 47%, mantle cell lymphoma 29% and follicular lymphoma 24%. In the 280 mg cohort, 2 patients had dose-limiting toxicity (DLT): 1 with transient syncope and 1 with periorbital cellulitis; at 560 mg, 1 patient had gastritis (grade 2). The RP2D was established at 560 mg ibrutinib. The most common (≥ 20% of patients) adverse events (AEs) were neutropenia (77%), thrombocytopenia (65%), vomiting (59%), anemia (53%), nausea (47%), fatigue (35%), headache (29%), constipation (24%), diarrhea (24%), and dizziness (24%). To date, 6 patients completed 6 cycles of treatment, and 2 patients discontinued treatment (1 due to noncompliance with the study drug and 1 due to non-DLT AE). At the time of this analysis, of the 10 patients had at least one post baseline tumor, the overall response rate was 100% (7 complete and 3 partial responses). Conclusions: The combination of IR-CHOP has an acceptable safety profile. No new toxicities were noted with adding ibrutinib to R-CHOP. An expansion cohort 560 mg ibrutinib (RP2D) is being opened to further explore the safety and efficacy of IR-CHOP in patients with newly diagnosed diffuse large B-cell lymphomas. Clinical trial information: NCT01569750.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5078-5078
Author(s):  
Marcelo Bellesso ◽  
Sergio Paulo Bydlowski ◽  
Renata Oliveira Costa ◽  
Felipe Vieira Rodrigues Maciel ◽  
Debora Levy ◽  
...  

Abstract Abstract 5078 Background: Low-affinity receptor for the Fcγ region of immunoglobulin G (IgG) (FcγR) is constitutively expressed on resting human neutrophils. These receptor, termed FcγRIIa display biallelic polymorphism which have functional consequences with respect to binding and/or ingestion of targets opsonized by human IgG subclass antibodies. Rituximab is a chimeric monoclonal antibody directed against CD20, an antigen found in most B-cell malignancies. Multiple mechanisms have been proposed for the activity of Rituximab, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and a direct proapoptotic effect. F(ab′)2 Rituximab homodimers were shown to be effective in inducing apoptosis of B-cell lymphoma cell lines in vitro. Recently, it have been established that ADCC is important as predominant mechanism of lymphoma cell clearance and that Fcγ receptors (FcγRs) are critical for the in vivo actions of Rituximab in non-Hodgkin lymphoma (NHL). A genomic polymorphism at amino acid 131 of FcγRIIA has been described whereby the presence of Histidine (H) rather than Arginine is associated with responses to the CD20-directed immunoglobulin G1 (IgG1) Rituximab among patients with indolent lymphoma. FcγRIIA genotype have been associated with a better clinical and molecular response in follicular lymphoma patients treated as first line therapy with Rituximab alone and in patients with diffuse large B-cell lymphoma (DLBCL) treated with the concomitant administration of Rituximab and CHOP (R-CHOP). Methods: Here we analyzed the role of specific polymorphism of activating FcγRIIA in 64 patients with DLBCL treated with R-CHOP concerning prediction complete response (CR), Progression Free Survival (PFS) and Overall Survival (OS) using a polymerase chain reaction-restriction fragment length polymorphism method. Results: The median age of the patients was 48.6 years. Out of the 64 patients (32%), were stage III-IV and 27 (42.5%) had more than 2 factors of the International Prognostic Index. Fity-six (89%) had CR and 7 (9.5%) had refractory disease (RD). Seven (11%) of the patients presented relapses. Deaths occurred in 6 (9.3%) patients with follow up of 19,5 months (range 21,3-50,1). The distribution of FcγRIIA polymorphism genotypes was: 15 (23,4%) HH, 30(46,9%) HR and 19(29,7%) RR, while considering only two groups (HH and R allele (HR and RR) was 15 (23,4%) and 49 (76,6%). There were no statistically significant differences in the genotypes groups according prognostic factors. In addition, there were not differences between response rate and FcγRIIA genotypes polymorphism: the CR in HH and HR/ RR were respectively 80% and 89%, p=0,377. It was not found differences regarding FcγRIIa. HH genotype presented a median PFS and OS. Thus, PFS HH genotype presented a median PFS 20,96 ± 10,49 months versus HR/RR median PFS 12,03 ± 7,71 months, p = 0,765, and OS 23,26 ± 10,42 months versus HR/ RR median OS 12,7 ± 7,42 months, p =0,98. Conclusions: Contrary to recent report we showed that FcγRIIA polymorphism is not associated to overall response, PFS and OS in patients with DLBCL treated with R-CHOP. Disclosures: No relevant conflicts of interest to declare.


2012 ◽  
Vol 54 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Tanin Intragumtornchai ◽  
Udomsak Bunworasate ◽  
Noppadol Siritanaratkul ◽  
Archrob Khuhapinant ◽  
Weerasak Nawarawong ◽  
...  

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Rachel Wong ◽  
Roopesh R. Kansara

Introduction Dose adjusted (DA) EPOCH-R is an intensive outpatient infusional regimen, that incorporates intrathecal (IT) methotrexate to treat patients with aggressive B-cell lymphoma including HIV associated aggressive B-cell lymphoma, double-hit lymphoma (DHL), primary mediastinal B-cell lymphoma (PMBCL), Burkitt's lymphoma (BL) ineligible for intensive therapy, and gray zone lymphoma (GZL) with features in between BL and diffuse large B-cell lymphoma (DLBCL). We aimed to evaluate non-trial, progression-free survival (PFS) and overall survival (OS) of Manitoba patients treated with DA-EPOCH-R, assess the role of prophylactic IT chemotherapy and toxicities. Methods Patients in MB approved to receive DA-EPOCH-R were identified through the CCMB Provincial Oncology Drug Program (PODP) database. Patients were included if they were older than 17 years, received at least 1 cycle of DA-EPOCH-R and with a diagnosis of HIV associated aggressive B-cell lymphoma, DHL, PMBCL, BL ineligible for more aggressive therapy, or GZL. All other diagnoses were excluded. Baseline demographic data, treatment characteristics, treatment responses, and treatment toxicity were collected. The primary endpoints of the study were progression free survival (PFS) and overall survival (OS). PFS was the time interval between the date of diagnosis to date of progression, last follow-up, or death from any cause. OS was the time interval between date of diagnosis to date of death by any cause, or last follow-up. The study was approved by the University of Manitoba Research Ethics Board and the CancerCare Manitoba Research Resource Impact Committee. Results A total of 40 patients were approved for DA-EPOCH-R between 2013 and 2019. 10 of these patients were excluded. 4 patients never received the therapy, 4 patients were treated in the relapsed setting, and 2 patients had histologies outside the inclusion criteria. Of the 30 patients included, 19 (63%) were male, 11 (37%) were female. The median age at diagnosis was 55 years (range 20-88). Our cohort was composed of DHL (n=9), triple hit lymphoma (THL, n=5), BL (n=4), GZL (n=3), and HIV-associated DLBCL (n=2). 87% (n=26) had advanced stage disease. By revised-IPI, 19 (63.3%) had poor prognosis (R-IPI ≥ 3). Response rate was 90%; CR 53.3% (n=16) and PR 37% (n=11). At a median follow-up of 25.3 months, the median PFS was 33.3 months and median OS was not reached. By histological subtype, median PFS was not reached in DHL, however THL, BL and PMBCL had worse median PFS (6.1, 8.4, and 5.6 months, respectively). Only 1 patient had CNS involvement at time of diagnosis. Of the patients with no documented CNS disease at presentation (n=29), none developed CNS involvement, including those who did not receive IT methotrexate. Median chemotherapy cycles per patient was 6 (range 1-6) and median IT treatment was 3 (range 0-6). 3 patients did not receive IT prophylaxis, and 2 stopped after 1 cycle due to intolerance. 56.7% (n=17) were able to undergo dose escalation beyond dose level 1, and 40% (n=T12) tolerated maximum dose level 3 or higher.77% of patients (n=23) experienced at least one adverse event of grade 3 or higher. 17 (57%) patients required blood transfusion at least once. 10 (33%) experienced neuropathy, 4 requiring vincristine dose reduction. 9 (30%) patients had febrile neutropenia complicating a total of 22 treatment cycles. 8 patients had grade 2-3 infectious complications. Conclusions While the real-world survival data for patients with DHL and HIV-associated lymphoma treated with DA-EPOCH-R are encouraging, those with THL, BL, and PMBCL did not attain durable response. Considering no patients (including those who did not receive IT chemotherapy) experienced CNS relapse, the role of IT chemotherapy needs to be further clarified. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 38 (29) ◽  
pp. 3377-3387
Author(s):  
Pieternella Johanna Lugtenburg ◽  
Peter de Nully Brown ◽  
Bronno van der Holt ◽  
Francesco A. D’Amore ◽  
Harry R. Koene ◽  
...  

PURPOSE Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compared with standard R-CHOP. PATIENTS AND METHODS A total of 574 patients with DLBCL age 18 to 80 years were randomly assigned to induction therapy with 6 or 8 cycles of R-CHOP-14 with (RR-CHOP-14) or without (R-CHOP-14) intensification of rituximab in the first 4 cycles. The primary end point was complete remission (CR) on induction. Analyses were performed by intention to treat. RESULTS CR was achieved in 254 (89%) of 286 patients in the R-CHOP-14 arm and 249 (86%) of 288 patients in the RR-CHOP-14 arm (hazard ratio [HR], 0.82; 95% CI, 0.50 to 1.36; P = .44). After a median follow-up of 92 months (range, 1-131 months), 3-year failure-free survival was 74% (95% CI, 68% to 78%) in the R-CHOP-14 arm versus 69% (95% CI, 63% to 74%) in the RR-CHOP-14 arm (HR, 1.26; 95% CI, 0.98 to 1.61; P = .07). Progression-free survival at 3 years was 74% (95% CI, 69% to 79%) in the R-CHOP-14 arm versus 71% (95% CI, 66% to 76%) in the RR-CHOP-14 arm (HR, 1.20; 95% CI, 0.94 to 1.55; P = .15). Overall survival at 3 years was 81% (95% CI, 76% to 85%) in the R-CHOP-14 arm versus 76% (95% CI, 70% to 80%) in the RR-CHOP-14 arm (HR, 1.27; 95% CI, 0.97 to 1.67; P = .09). Patients between ages 66 and 80 years experienced significantly more toxicity during the first 4 cycles in the RR-CHOP-14 arm, especially neutropenia and infections. CONCLUSION Early rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.


2020 ◽  
Author(s):  
Hsu-Chih Chien ◽  
Deborah Morreall ◽  
Vikas Patil ◽  
Kelli M Rasmussen ◽  
Chunyang Li ◽  
...  

Aim: To describe practices and outcomes in veterans with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Using Veteran Affairs Cancer Registry System and electronic health record data, we identified relapsed/refractory diffuse large B-cell lymphoma patients completing second-line treatment (2L) in 2000–2016. Treatments were classified as aggressive/nonaggressive. Analyses included descriptive statistics and the Kaplan–Meier estimation of progression-free survival and overall survival. Results: Two hundred and seventy patients received 2L. During median 9.7-month follow-up starting from 2L, 470 regimens were observed, averaging 2.7 regimens/patient: 219 aggressive, 251 nonaggressive. One hundred and twenty-one patients proceeded to third-line, 50 to fourth-line and 18 to fifth-line treatment. Median progression-free survival in 2L was 5.2 months. Median overall survival was 9.5 months. Forty-four patients (16.3%) proceeded to bone marrow transplant. Conclusion: More effective, less toxic treatments are needed and should be initiated earlier in treatment trajectory.


2018 ◽  
Vol 13 (1) ◽  
Author(s):  
Mubarak M. Al-Mansour ◽  
Saif A. Alghamdi ◽  
Musab A. Alsubaie ◽  
Abdullah A. Alesa ◽  
Muhammad A. Khan

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2817-2817 ◽  
Author(s):  
Kerry J. Savage ◽  
Mukesh Chhanabhai ◽  
Nicholas Voss ◽  
Shenkier Tamara ◽  
Randy D. Gascoyne ◽  
...  

Abstract Background: Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of diseases with an overall poor prognosis. Little information is available regarding the outcome of PTCL patients who present with limited stage disease. We sought to determine the outcome of PTCL patients presenting with limited disease in comparison with a cohort of patients with limited stage diffuse large B-cell lymphoma (DLBCL). Methods: In a retrospective analysis we identified all patients with limited stage (non-bulky (<10cm) stage I/II disease no symptoms) PTCL diagnosed at the British Columbia Cancer Agency (BCCA) between 1983 and 2004. Patients were excluded if they had cutaneous anaplastic large cell lymphoma (CutALCL) (n=13), NK/T-cell lymphoma nasal type (n=9) or primary CNS/ocular involvement (n=6). Results: Thirty-seven patients with PTCL were identified according to the World Health Organization Classification: ALK-neg ALCL 8 (22%); PTCL-unspecified (PTCLUS) 28 (78%); enteropathy associated TCL (EATL) 1 (3 %). The majority received CHOP-type chemotherapy (n=31, 86%), most with brief chemotherapy followed by involved-field radiation (n=19, 61%). The 5 y OS and PFS was similar between PTCLUS and ALK-neg ALCL. There was no difference in survival between extranodal and nodal cases. The outcome of PTCL patients (including ALK-neg ALCL and PTCLUS) was compared to a cohort of limited stage DLBCL patients (excluding CNS/ocular lymphoma) (n=305) diagnosed over the same time period and treated similarly. There was no difference in 5 y OS or PFS (Figure 1,2). Interestingly, there were no late relapses observed in PTCLUS, in marked contrast to DLBCL. Conclusions: Limited stage PTCL is rare, however outcomes appear to be comparable to early stage DLBCL, supporting that they should be treated in a similar manner. Unlike limited stage DLBCL where late relapses occur, a plateau in the progression-free survival curve is observed, highlighting a distinct natural history for limited stage PTCL. Overall Survival Limited Stage PTCL vs DLBCL p=.18 Overall Survival Limited Stage PTCL vs DLBCL p=.18 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07


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