Intermediate Dose Methotrexate Improves Overall Survival and Progression-Free Survival of Patients with Diffuse Large B Cell Lymphoma Treated with the R-CHOP or CHOP Regimen

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2698-2698 ◽  
Author(s):  
Eldad J Dann ◽  
Vered Heffes ◽  
Tatiana Mashiach ◽  
Noam Benyamini ◽  
Irit Avivi ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Stage Iv ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Cns Involvement ◽  
Chop Regimen ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Large B Cell

Abstract Introduction: Patients (pts) with diffuse large B cell lymphoma (DLBCL) and high International Prognostic Index (IPI) or extra-nodal localization are at a higher risk for relapse with central nervous system (CNS) involvement. The current policy at the Rambam Health Care Campus (Haifa, Israel) is to give DLBCL pts 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) together with 4 doses of intrathecal (IT) methotrexate (MTX), which may be followed by 2 additional cycles of an intermediate dose (3 g/m2) of intravenous MTX (ID-MTX). The present study aimed to compare the outcome of DLBCL pts with risk factors for CNS relapse who did or did not receive prophylaxis with ID-MTX. Methods: We retrospectively evaluated a cohort of DLBCL pts treated at Rambam between the years 1991 and 2012. Overall survival (OS), progression-free survival (PFS) and CNS involvement at relapse were estimated in 203 of 355 pts [96 females, 107 males; median age 59 (range18-90) years]. The study included all pts with the primary diagnosis of DLBCL and risk factors for CNS relapse, i.e., Waldeyer ring (5%), breast (2%), testicular (3%), orbital (1%) involvement, bone marrow involvement (25%), stage IV disease (63%), LDH > normal (68%), ≥1 extra-nodal site (26%), IPI ≥3 (41%). Ten percent of pts had stage I-IE disease, 15% - stage II-IIE, 12% - stage III, 63% - stage IV, 38% had B symptoms. Pts with CNS involvement at diagnosis were excluded from the study. Results: One hundred and fifty patients (74%) were treated with R-CHOP. In this group, 40% of pts with IPI=0/1, 29% with IPI=2 and 47% with IPI ≥3 received ID-MTX prophylaxis. Sixty four pts received ID-MTX (32%), 14 pts (7%) received IT MTX only, 125 pts had no prophylaxis (62%). At a median follow-up of 92 months, 5% of pts had CNS relapse with no difference in incidence between the study groups. Pts with IPI≥3 treated with ID-MTX had a reduced overall relapse rate and significantly better PFS and OS (table 1). Conclusion: The addition of 2 cycles of ID-MTX to the R-CHOP regimen improved both PFS and OS of DLBCL pts with IPI≥3. A randomized controlled study is warranted to provide stronger evidence. Table 1. All patients Pts No. PFS % P *HR 95% CI P OS % #HR 95% CI ID-MTX 65 60 1 88 1 IT MTX 15 56 0.09 1.92 0.9-4.1 0.008 43 3.27 1.4-7.8 No prophylaxis 123 42 0.04 1.58 1.0-2.49 0.002 51 2.49 1.4-4.4 R-CHOP Data IPI≥3 no prophylaxis 35 20 1 26 1 IPI≥3 +ID-MTX 31 58 0.004 0.38 0.29-0.85 0.001 67 0.29 0.14-0.6 No.: number; *HR: hazard ratio for progression; #HR for mortality; CI: confidential interval Disclosures No relevant conflicts of interest to declare.

scholarly journals Addition of Intermediate-Dose Methotrexate Is Beneficial in Terms of Both Progression-Free Survival and Overall Survival for Patients with Diffuse Large B Cell Lymphoma Receiving Either R-CHOP or CHOP

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1877-1877 ◽  
Author(s):  
Eldad J. Dann ◽  
Neta Goldschmidt ◽  
Vered Heffes ◽  
Tanya Mashiach ◽  
Moshe E. Gatt ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Stage Iv ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Cns Involvement ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Large B Cell ◽  
Intermediate Dose

Abstract Introduction: Patients with diffuse large B cell lymphoma (DLBCL) and high International Prognostic Index (IPI) or extra-nodal disease are at an increased risk of systemic and central nervous system (CNS) relapse. Presently, the management of DLBCL patients at the Rambam Health Care Campus (Haifa, Israel) and Hadassah Medical Center (Jerusalem, Israel) includes 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) along with 4 doses of intrathecal (IT) methotrexate (MTX), which may be followed by 2 additional cycles of an intermediate dose (3 g/m2) of intravenousMTX (ID-MTX). The current study compared progression-free survival (PFS), overall survival (OS) and CNS relapse rate in a cohort of DLBCL patients with risk factors for CNS relapse who did or did not undergo prophylactic therapy with ID-MTX. Methods: Four hundred and eighty DLBCL patients treated at two tertiary care centers (Rambam and Hadassah) between the years 1991 and 2013 were retrospectively evaluated. The cohort included 224 females and 256 males at a median age of 58 years (range18-76). OS, PFS and CNS involvement at relapse were analyzed. The study incorporated all patients with the primary diagnosis of DLBCL and risk factors for CNS relapse, i.e., Waldeyer ring (2%), breast (1%), testicular (3%) or orbita (1%) involvement, bone marrow involvement (21%), stage IV disease (64%), LDH higher than normal (70%), ≥1 extra-nodal site (28%), IPI ≥3 (36%). Eight percent of patients had stage I-IE disease, 17% - stage II-IIE, 11% - stage III, 64% - stage IV, 29% had B symptoms. Patients with CNS involvement at diagnosis were excluded from the analysis. Results: Four hundred and seventy three patients (99%) were treated with either CHOP or CHOP-like regimen, and 384 (80%) patients received rituximab (R). In the R-CHOP cohort, 23% of patients with IPI 0/1, 28% with IPI 2 and 42% with IPI ≥3 were given prophylaxis. One hundred and thirty patients received ID-MTX (27%), 35 patients (7%) received IT-MTX only, while no prophylaxis was administered to 315 patients (66%). The cumulative incidence of CNS relapse at 5 years was 6%, with no difference in the incidence between the patients who received prophylaxis with ID-MTX, IT-MTX or were given no prophylaxis at all. Patients with IPI ≥3 treated with ID-MTX had a decreased overall relapse rate and significantly superior OS and PFS (Table 1; Figure 1). Conclusion: In the current study, the addition of two cycles of ID-MTX to the standard R-CHOP regimen resulted in improved 5-year PFS and OS of DLBCL patients with IPI ≥3. These data need to be further confirmed in a randomized controlled study. Disclosures No relevant conflicts of interest to declare.

EFFICACY AND SIDE EFFECTS OF R-CHOP REGIMEN IN PATIENTS WITH DIFFUSE LARGE B-CELL CD20 POSITIVE LYMPHOMA AT HUE UNIVERSITY OF MEDICINE AND PHARMACY HOSPITAL

2018 ◽  
Vol 8 (3) ◽  
pp. 48-53 ◽  
Author(s):  
Thai Le Trong ◽  
Toan Le Duy ◽  
Khoi Tran Viet ◽  
Bao Tran Quoc ◽  
Tung Pham Tang ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Chop Regimen ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Grade Iii

Background: Non-Hodgkin lymphomas (NHL) ranks 10 among the top 15 common cancers worldwide. Diffuse large B-cell lymphoma (DLBCL) is the most common type of the disease. Despite malignancy, DLBCL is curable and sensitive to chemotherapy and radiation therapy. Since first published in 1997, the protocol R-CHOP, a combination of classical chemotherapy CHOP with rituximab, has increased significantly the rate of complete response (CR) and improved overall survival (OS). However, there has been no report of R-CHOP treatment in Hue. Purpose of this research is to evaluate the efficiency of R-CHOP treatment (complete response, progression-free survival) and to describe the toxicities of the protocol. Methods: A retrospective cohort study on 36 patients with diffuse large B-cell lymphoma, CD 20 positive treated with R-CHOP at Hue University Hospital between 2011 and 2016. Results: According to the International prognostic index (IPI), 15 patients (41.7%) had low-risk disease, 14 (38.9%) low-to-intermediate risk, 6 (16.7%) high-to-intermediate risk and 1 (2.7%) high-risk disease. After finishing 8 cycles of therapy, 19 patients (52.8%) achieved complete response. Grade III anemia was observed (13.9%), grade III neutropeniain 4 patients (11.1%) and nausea (5.6%). During a 5-year period, progression – free survival was reported for 66.7% of patients and median for survival time was 3.3 years. Conclusions: The addition of rituximab to the CHOP regimen increases the complete-response rate and prolongs progression -free survival in patients with diffuse large-B-cell lymphoma. The treatment of R-CHOP is well tolerated that the adverse events are mostly reported at grade III and able to control effectively. Key words: diffuse large B-cell, non-hodgkin lymphoma, CD20 positive, CHOP, rituximab

Additional Two Cycles of Rituximab Improves the Prognosis of Low-Risk NCCN-IPI Diffuse Large B-Cell Lymphoma Patients Responded to R-CHOP Regimen

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2733-2733
Author(s):  
Pengpeng Xu ◽  
Huijuan Zhong ◽  
Weili Zhao
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Low Risk ◽  
Chop Regimen ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas with a relapse/refractory rate of 30-40% under the current standard Rituximab plus cyclophophamide, adrimycin, vincristine and prednisone (R-CHOP21) treatment. As mechanism of action, Rituximab can target the B-cell receptor (BCR) and NF-ĸB signaling pathways, of which activating gene mutations are most frequently identified in activated B-cell-like (ABC) subtype of DLBCL and associated with increased disease relapse of the patients. The aim of our study was to investigate the clinical efficacy of additional two cycles of Rituximab maintenance (RM) in DLBCL and its relation with mutational status involved in BCR/NF-ĸB cascade. Methods: We retrospectively analyzed a total of 534 de novo DLBCL patients after 6 cycles of R-CHOP21 regimen in our institution from December 1998 to December 2012. Among 413 patients achieved complete response (CR), 211 patients received additional 2 cycles of RM in a intent-to-treat manner and 202 patients underwent observation (OBS). The remaining 121 patients were primarly refractory to R-CHOP regimen. All the patients were classified according to IPI and NCCN-IPI as previously described. Immunohistochemistry for germinal center B-cell (GCB) or non-GCB subgroups were determined by Hans classification. The mutational status of BCR/NF-ĸB-associated genes (mainly as CD79A, CD79B, MYD88, and CARD11) were detected in tumor samples of 124 patients (48 cases, 43 cases and 33 cases in the RM, OBS and Refractory group, respectively). Results: No significant difference of clincial and biological characteristics were found between the RM and OBS group, including age, gender, Ann Arbor stage, ECOG score, number of extranodal involvements, serum lactic dehydrogenase level, B symptoms, IPI and NCCN-IPI risk group, and GCB/non-GCB ratio. With a median follow-up of 36.5 months, the 3-year progrssion free survival (PFS) was 79.9% and 73.6% (P=0.123), and the 3-year overall survival (OS) was 91.0% and 87.4% (P=0.149) in RM and OBS group, respectively. According to NCCN-IPI, remarkable improvement of 3-year PFS and OS was observed in low-risk patients of the RM group (100% and 100%), comparing with those of the OBS group (82.5% and 88.2%, P=0.003 and 0.027 respectively, Figure 1). Similarly, male patients with low-risk IPI could also benefit from additional 2 cycles of Rituximab with a 3-year PFS of 100% in RM vs 84.4% in OBS (P=0.006). Overall, BCR/NF-ĸB mutations were detected in 46/124 patients (37.1%), including 20/48 (41.7%), 13/43(30.2%) and 13/33 (39.4%) patients in RM, OBS and Refractory group, respectively. However, MYD88 mutations were more frequently observed in the Refractory group than in the RM/OBS group (18/33 vs 6/91, P<0.001, Table 1). Mutations are not prognostic indicators for PFS or OS in general, but interestingly, those mutation-bearing patients showed a tendency of improved disease prognosis in the RM group compared with that of the OBS group (3-year PFS 85.5% vs 70.0%, P=0.091, 3-year OS 94.7% vs 71.6%, P=0.059, Figure 2). Conclusion: Low-risk NCCI-IPI patients with DLBCL responded to R-CHOP regimen benefit from additional two cycles of RM. As a potential target of Rituximab, BCR/NF-ĸB-associated mutations reflected disease resistance to Rituximab. Whether prolonged administration of Rituximab could improve the prognosis of the patients with these mutations warrants further investigation. Table 1. The distribution of BCR/NF-κB-associated mutations in patients with DLBCL Mutated gene Refractory (N=33) CR (N=91) Additional 2R (N=48) Observation (N=43) P value CD79a 1 (3.0%) 0 (0%) 0 (0%) 0.595a CD79b 5 (15.1%) 10 (20.8%) 6 (13.9%) 0.750 a MYD88 18 (54.5%) 3 (6.0%) 3 (6.9%) <0.001b CARD11 1 (3.0%) 7 (14.0%) 4 (9.3%) 0.244a a: No significantly difference was found between Refractory group and CR group. b: Significantly difference was found between Refractory group and CR group (p<0.05). Figure 1. Progression-free survival (A) and overall survival (B) curves of diffuse large B-cell lymphoma patients according to low-risk NCCN-IPI. Figure 1. Progression-free survival (A) and overall survival (B) curves of diffuse large B-cell lymphoma patients according to low-risk NCCN-IPI. Figure 2. Progression-free survival (A) and overall survival (B) curves of diffuse large B-cell lymphoma patients with BCR/NF-ĸB-associated mutations. Figure 2. Progression-free survival (A) and overall survival (B) curves of diffuse large B-cell lymphoma patients with BCR/NF-ĸB-associated mutations. Disclosures No relevant conflicts of interest to declare.

Inferior progression-free survival for Thai patients with diffuse large B-cell lymphoma treated under Universal Coverage Scheme: the impact of rituximab inaccessability

2012 ◽  
Vol 54 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Tanin Intragumtornchai ◽  
Udomsak Bunworasate ◽  
Noppadol Siritanaratkul ◽  
Archrob Khuhapinant ◽  
Weerasak Nawarawong ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Universal Coverage ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Universal Coverage Scheme ◽  
Large B Cell

scholarly journals Rituximab-CHOP With Early Rituximab Intensification for Diffuse Large B-Cell Lymphoma: A Randomized Phase III Trial of the HOVON and the Nordic Lymphoma Group (HOVON-84)

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 ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival ◽  
Intention To Treat ◽  
Large B Cell Lymphoma ◽  
Large B Cell

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.

scholarly journals Real-world practice patterns and outcomes in Veterans with relapsed/refractory diffuse large B-cell lymphoma

2020 ◽  
Author(s):  
Hsu-Chih Chien ◽  
Deborah Morreall ◽  
Vikas Patil ◽  
Kelli M Rasmussen ◽  
Chunyang Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Line Treatment ◽  
Electronic Health Record Data ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

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.

scholarly journals Negative effect of hepatitis in overall and progression-free survival among patients with diffuse large B-cell lymphoma

2018 ◽  
Vol 13 (1) ◽  
Author(s):  
Mubarak M. Al-Mansour ◽  
Saif A. Alghamdi ◽  
Musab A. Alsubaie ◽  
Abdullah A. Alesa ◽  
Muhammad A. Khan
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Negative Effect ◽  
Large B Cell

Survival of Limited Stage Peripheral T-Cell Lymphoma Is Similar To Diffuse Large B-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2817-2817 ◽  
Author(s):  
Kerry J. Savage ◽  
Mukesh Chhanabhai ◽  
Nicholas Voss ◽  
Shenkier Tamara ◽  
Randy D. Gascoyne ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Limited Stage ◽  
Large B Cell Lymphoma ◽  
Large B Cell

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

Sign in / Sign up

Export Citation Format

Share Document