Primary Mediastinal Large B-Cell Lymphoma: Investigation On The Role Of Rituximab and PET During Treatment

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3046-3046 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Cinzia Pellegrini ◽  
Beatrice Casadei ◽  
Enrico Derenzini ◽  
Alessandro Broccoli ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Additional Treatment ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Disease Free ◽  
Large B Cell

Abstract Due to limited prospective studies, the optimal treatment of primary mediastinal large B-cell lymphoma (PMLBCL) is still a matter of debate. Third-generation MACOP-B (adriamycin, cyclophosphamide, vincristine, bleomycin, methotrexate and prednisone) regimen in combination with mediastinal radiotherapy (RT) seems to improve disease free survival of patients. In addition, the impact of additional treatment with rituximab and the role of PET are still under investigation due to controversial reported results. As per institutional guidelines, MACOP-B plus RT was recommended in all PMLBCL patients until 2002. Aim of this report was evaluate the outcome of PMBCL patients diagnosed and treated with MACOP-B plus rituximab and consolidative mediastinal RT (30-36 Gy) after 2002. PET role was also investigated. Seventy-four patients were deemed eligible for this study (follow up of at least 2 years). Fifty patients had stage II and 24 stage IIE-IV, bulky disease was documented in 93% of patients. Median age was 34 years (range, 17-62) and 59.5% were females. All patients were evaluated by both CT and PET scan. After the final PET evaluation, PET-negative patients were observed while PET-positive patients underwent mediastinal RT. At the end of treatment, 61 (82.4%) patients achieved a complete response (CR); 51 (68.9%) presented a positive final PET and were treated with local RT, while the other 23 (31.1%) had a negative PET. Five patients relapsed within 12 months. At 10 years, estimated overall survival was 82%, progression-free survival was 87.6% and disease-free survival (DFS) for the 61 CR patients was 90.5% (median follow-up 4 years). Regarding the DFS curve (figure 1), no statistically significant differences were observed between patients who underwent also RT (PET-positive, group 1) and patients who remained under observation (PET-negative, group 2): 90.7% (4/51 relapses) vs 90% (1/23 relapse) (p= 0.85), respectively. Comparing these results with our institutional historical series when the front-line for PMLBCL patients included only MACOP-B plus RT without any decision related to PET results (before 2002), the 10-year DFS resulted lower, i.e. 82.8%. Although with the limitations of an observational retrospective study, the present report underlines that the additional treatment with rituximab does not change the final results in terms of CRs and DFS utilizing third-generation regimens. Moreover, the introduction of the PET-guided RT approach after MACOP-B plus rituximab allows a patient tailored strategy which reduces the use of RT and preserves clinical outcomes. Figure 1 Figure 1. Disclosures: No relevant conflicts of interest to declare.

Efficacy of RICE as Second Line Chemotherapy in Transplant Ineligible Patients with Diffuse Large B Cell Lymphoma: a Single Institution Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4757-4757
Author(s):  
Mousami Shah ◽  
Shylendra B Sreenivasappa ◽  
Barbara Yim ◽  
Bety Ciobanu ◽  
Rosalind Catchatourian
Keyword(s):  
Cell Lymphoma ◽  
Disease Free Survival ◽  
Stage Iv ◽  
B Cell Lymphoma ◽  
Second Line ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Line Therapy ◽  
Disease Free ◽  
Large B Cell

Abstract Abstract 4757 Background The response of patients with relapse/refractory (s/p CHOPR) Diffuse large B Cell Lymphoma (DLBCL) to RICE chemotherapy in transplant ineligible patients (pts) is not well studied. Methods 28 consecutive pts with DLBCL, relapsed/refractory to CHOPR chemotherapy diagnosed in 2003 to 2008 were studied as a retrospective cohort for clinical presentation, prognostic characteristics and long term survival. Prognostic characteristics and survival was analyzed using fisher's exact test, exact logistic regression and Kaplan Meier analysis. Multiple imputation methods were used for missing data. Results 28 pts, 11(39%) were female, 17(61%) male. 11 (39.3%) African Americans, 12 (42.9%) Hispanic, 3 (11%) Caucasian and 2 (7%) Asians. 3 (10.7%) presented with stage I at diagnosis, 1(3.6%) stage II, 5(17.9%) stage III and 19 (67.9%) stage IV. The median age at diagnosis was 50.5 years (yrs) (22-71). 4 (14.3%) presented with stage I, 5(17.9%) stage II, 9(32.1%) stage III, 10(35.7%) stage IV. 14(50%) had intermediate risk Revised IPI score, 14 (50%) had high risk disease at presentation. 21(75%) had relapse and 7(25%) had refractory disease. Median time to relapse was 12 months (0-40). Median age at relapse was 51.5 yrs (23-72). 4 (14.3%) presented with stage I at relapse, 5 (17.9%) stage II, 9(32.1%) stage III and 10 (35.7%) stage IV. 12(42.8%) had intermediate risk R-IPI score at relapse and 16(57.2%) had high risk R-IPI score. The median follow up was 30 months (8-60). All patients received first line therapy with CHOPR 6-8 cycles. RICE was used as second line therapy. Median number of cycles was 4 (1-7). 10 (35.7%) had a complete response. 13 (46.4%) had partial response and 5 (17.9%) had progression of disease. Disease free survival was 10 months (0-55). Median overall survival was 30.5 months (8-60). There was no treatment related mortality. Extra nodal involvement (p=0.0094) was the only factor that significantly influenced response to RICE chemotherapy. Race (p=0.081) had boarder line significance with African American having poor response compared to other race. Pt with relapsed disease (p=0.013) and extra nodal involvement at relapse (p=0.049) had better disease free survival. The LDH at presentation (p=0.012), no extra nodal involvement at presentation (p=0.004), relapsed disease (p=0.048) and CR to RICE (0.001) significantly influenced overall survival. Conclusion In transplant ineligible patients with relapsed/refractory Diffuse Large B Cell Lymphoma, RICE can be considered as a second line therapy with a response rate of over 80%. The median disease free survival was 10 months, overall survival was 30.5 months. Pt with lower LDH and chemo sensitive disease had better over all survival. Poor response of African Americans to second line chemotherapy needs to be further investigated. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of the Association between Tgl and EZH2 Mutations (Y641N/Y641F/Y641H/Y641S) on Disease Free Survival of Patients with Diffuse Large B-Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5222-5222
Author(s):  
Myrna Candelaria ◽  
Adriana Palacios Campos ◽  
Olga Gutierrez Hernandez ◽  
Alejandro Aviles ◽  
Uvi Cancino-Ramos ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Pet Ct ◽  
18F Fdg ◽  
Disease Free ◽  
Large B Cell

Background: Diffuse Large B Cell Lymphoma (DLBCL) is the most frequent type of non-Hodgkin lymphoma. Although PET/CT has allowed a better diagnostic evaluation in these patients, none metabolic index has been incorporated into prognostic scores, neither molecular markers have been associated with PET/CT findings. Aim: To define the association between PET/CT findings and EZH2 mutations, and their impact on survival of patients with DLBCL. Methods: Patients: A cohort study of newly diagnosed DLBCL patients. Cohorts were defined according to the presence of EZH2 (Y641N/Y641F/Y641H/Y641S) mutations. Clinical variables were: age, comorbidities, IPI score, bulky disease, clinical stage, serum albumin, LDH and B2-microglobulin levels, and ECOG. Histopathologic variables were GC (Germinal center) versus no-GC by Hans nomogram, BCL2, BLC6, & MYC expression, as well as double-hit. All patients were treated with six cycles of standard RCHOP. PET/CT assessed parameters were: Total metabolic tumor volume (TMV), Total lesion glycolysis (TLG) and SUV max. Clinical response was evaluated by PET/CT, using Deauville's criteria. All 18F-FDG PET/CT scans were performed using the Biograph 16 PET/CT scanner (Siemens AG, Munich, Germany). Patients fasted for at least 6 h prior to intravenous (IV) administration of 18F-FDG (5.5 MBq/kg body weight) to ensure a serum glucose level of <10 mmol/l. Methods: DNA was extracted from paraffin-embedded tissue. PCR analysis was carried out in a 2700 Thermalcycler (Applied Biosystems) to detect mutations in Exon 16 of EZH2; the sequencing and electrophoresis of PCR products was performed using ABI3100 genetic analyser. Sequences were compared with the EZH2 reference sequence (GenBank NG_032043.1). The protocol was approved by IRB (Approval number CEI/966/15). Statistics: After descriptive analysis, mean metabolic indexes were compared by ANOVA between patients with wt and any of the EZH2 mutations . Kaplan-Meier method was used to construct Disease-free survival (DFS) curves and the Log-rank test was used for comparisons. COR curves were used to evaluate metabolic indexes as risk factors infuencing on DFS. Results: Results: 230 patients (120 male), were included. Median age was 58.3 years (SD 14.25; range: 21-91); 169 of them (73.4%) had advanced disease and 224 (97.3%) had ECOG <2. Absence of B symptoms or bulky disease was documented in 154 (67%) and 136 cases (59.1%), respectively. GC-type was found in 65%. Although sixty cases (26%) were considered to be DLBCL double expressor (MYC +BLC2 overexpression), only 15% were double-hit DLBCL. Mutations at codon 641, exon 16 of EZH2 were described in 15% of cases, as follows: Tyr 641 Asn (Y641N) [6 %],Tyr 641 Phe(Y641F) [6%], Tyr 641 His (Y641H) [3%] and Tyr 641Ser (Y641S) [1%]. Any clinical parameter was different between wt and any EZH2 mutations. However, regarding metabolic indexes by PET/CT, TLG was higher in EZH2 mutated patients (mean: 8314.02g [95 %CI: 5623-11004g]), in comparsion with wt patients (mean: 5228.99g, [ 95 % CI: 4114-6316g], p=0.02). Response was classified as complete in 75% of cases, partial in 3.5%, and progressive disease in 11%. The association of these mutations on DFS is shown in table 1. In addition, mean TLG and TMV indexes were lower in patients without relapse. (Table 2) Summary/Conclusion: These preliminary results suggest that patients with any of EZH2 (Y641F) mutations have a higher TLG by PET/CT at diagnosis, and both values have a negative impact on DFS of patients with DLBCL. Our results need to be confirmed on a larger sample and a longer follow-up. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Treatment of Primary Mediastinal Large B-Cell Lymphoma: A Two Decades Monocentric Experience on 98 Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4440-4440
Author(s):  
Beatrice Casadei ◽  
Alessandro Broccoli ◽  
Vittorio Stefoni ◽  
Cinzia Pellegrini ◽  
Letizia Gandolfi ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Third Generation ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
First Line Treatment

Abstract The first line treatment for primary mediastinal large B-cell lymphoma (PMLBCL) still remains a matter of debate even if the literature confirms that an anthracycline-containing regimen should be the main choice. The European experience shows the superiority of “third-generation” dose-dense regimen like MACOP-B (methotrexate, doxurubicin, cyclophosphamide, vincristine, bleomycin, prednisone) or VACOP-B (same as MACOP-B, with etoposide instead of methotrexate) over CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) or CHOP-like regimen. The addition of rituximab to third-generation regimen does not seem to cause any advantages in terms of overall survival (OS) and progression free-survival (PFS), while external radiotherapy (RT) has shown a good efficacy as a consolidation strategy at the end of induction chemotherapy, especially in converting partial responses (PR) into complete responses (CR). Between October 1989 and April 2010, 98 (58 females and 40 males) previously untreated PMLBCL patients were diagnosed and subsequently treated at our Institution. All patients were treated with MACOP-B regimen, concurrent rituximab was administered in 57 patients (58.2%) and 67 patients (68.4%) received mediastinal RT. Among 57 patients who received rituximab, 37 (64.9%) underwent RT whereas, among 41 who did not receive rituximab, RT was delivered in 30 (group 4, 73.2%) patients. 11 patients (group 1, 11.2%) received chemotherapy alone and 37 (group 3, 37.8%) received besides immunotherapy and RT (Table 1). All patients were assessed at the diagnosis and after the treatment with computed tomography and positron emission tomography (after 2001) scan. Main aims of our study were the effectiveness of the regimen measured as overall response rate (ORR) and patients survival. Sixty-one (62.2%) out of 98 patients achieved a CR and 27 (27.6%) were in PR after 12 cycles of MACOP-B regimen (with or without rituximab). Twenty-one patients in PR after (immuno)chemotherapy converted the response into CR with mediastinal RT. At the end of the scheduled treatment, 82 patients (83.7%) achieved a CR and 6 a PR (6.1%), yielding an ORR of 89.8%. At a median follow-up of 5.6 years, 9 patients relapsed within the first 2 years of treatment. During the follow-up 15 patients died, of whom 13 as a consequence of disease relapse or progression. The projected OS at 17 years is 72% with a PFS and a disease free survival (DSF) of 86.8% and 88.4% respectively (Figure 1 A-C). The subgroup analysis shows a statistically significant difference in term of OS (p=0.0003) but not in term of PSF and DFS among the four groups of treatment (Figure 1 D-F). All the patients receiving consolidation RT obtained a CR without differences between subgroup 3 and 4. RT seems to have a small consolidative potential in patients who obtained CR after chemo-immunotherapy alone: there are no differences in term of DFS between subgroup 2 and 3. No statistically significant differences in terms of OS, PFS and DSF occurred among patients received rituximab or not, regardless of a subsequent RT. Our monocentric experience spans a period of 20 years and indicates that a third-generation regimen like MACOP-B is feasible and could be a standard of first line treatment for PMLBCL. In agreement with the literature, adding rituximab doesn’t improve the outcome. Mediastinal RT, delivered as a consolidative strategy, impacts on global survival and on CR rates. In particular, RT after third-generation regimen remains a good strategy to convert PR into CR, but it may be avoided in patients obtaining CR after (immuno)chemotherapy. Table 1 Group MACOP-B Rituximab Radiotherapy N (%) 1 Yes No No 11 (11.2%) 2 Yes Yes No 20 (20.4%) 3 Yes Yes Yes 37 (37.8%) 4 Yes No Yes 30 (30.6%) TOTAL N (%) 98 (100%) 57 (58.2%) 67 (68.4%) 98 (100%) Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Emerging Role of Consolidative Radiotherapy After Complete Remission Following R-CHOP Immunochemotherapy in Stage III–IV Diffuse Large B-Cell Lymphoma: A Single Institutional and Case-Matched Control Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Ji Hyun Hong ◽  
Han Hee Lee ◽  
Seung-Eun Jung ◽  
Gyeongsin Park ◽  
Joo-Hyun O ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Complete Remission ◽  
Head And Neck ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Consolidative Radiotherapy ◽  
Large B Cell

PurposeThe role of consolidative radiotherapy (RT) after complete-remission (CR) following rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in advanced-stage diffuse large B-cell lymphoma (DLBCL) remains unclear. We retrospectively analyzed the survival outcomes and patterns of failure with our institutional experience.Material and MethodsBetween 2009 and 2018, 206 patients with stage III-IV DLBCL achieved CR after receiving R-CHOP. Propensity-score matching was used to analyze the role of consolidative RT. The consolidative RT group (n = 34) and the R-CHOP alone group (n = 68) were matched at a 1:2 ratio. After propensity-score matching, 102 patients were analyzed.ResultsWith a median follow-up of 39.7 months, 26 patients (25.5%) showed local recurrence. Only one patient failed at the previous RT field. RT was delivered to bulky sites, head and neck lesions, testes, and bone with median dose of 30.6 Gy. The most common site of failure was head and neck lesions followed by bulky sites. The 5-year overall survival (OS), progression-free survival (PFS), and isolated-local recurrence free survival (LRFS) were 73.5, 64.0, and 79.9%. In univariate and multivariate analysis, bone marrow involvement and consolidative RT were associated with isolated LRFS (p = 0.006 and 0.032) significantly.ConclusionConsolidative RT improved isolated local control. Based on the pattern of failure, we carefully suggest to radiate on initially involved bulky sites or head and neck lesions. Further studies need to be done to find out the optimal radiation dose and selection of RT site.

scholarly journals Extra copies of MYC, BCL2, and BCL6 and outcome in patients with diffuse large B-cell lymphoma

2020 ◽  
Vol 4 (14) ◽  
pp. 3382-3390
Author(s):  
David Sermer ◽  
Sabela Bobillo ◽  
Ahmet Dogan ◽  
Yanming Zhang ◽  
Venkatraman Seshan ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Similar Frequency ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Gene Copies ◽  
Single Center Study ◽  
Large B Cell

Abstract High-grade B-cell lymphoma (HGBL) with translocations involving MYC and BCL2 or BCL6 comprises ∼10% of cases of diffuse large B-cell lymphoma (DLBCL) and carries a poor prognosis. The incidence, prognosis, and optimal therapy for DLBCL harboring extra copies of the genes MYC, BCL2, and BCL6, rather than their genetic translocations, are unknown. In this retrospective, single-center study we identified 144 DLBCL cases including 46 patients with classic HGBL with double-hit or triple-hit chromosomal translocations (DHL), 55 with extra copies of MYC in addition to aberrations (extra copies or translocations) of BCL2 and/or BCL6 but did not meet the criteria for HGBL (EC group), and 43 without any aberrations of MYC, BCL2, or BCL6 (wild type [WT]). Unfavorable baseline characteristics had similar frequency in the EC and WT groups, but were significantly more prevalent in the DHL group. With a median follow-up of 36 months, the 2-year event-free survival (EFS) was similar between the WT and EC groups at 77% (95% confidence interval [CI], 65-90) and 82% (95% CI, 72-93), respectively. In contrast, the 2-year EFS of the DHL group was 63% (95% CI, 51-79). The 2-year overall survival in the WT, EC, and DHL groups was 86% (95% CI, 76-97), 89% (95% CI, 81-98), and 74% (95% CI, 62-88), respectively. Among patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the EC group had outcomes similar to those of the WT group. Our results indicate that patients with DLBCL with extra gene copies of MYC, BCL2, and BCL6 fare differently from those with HGBL and respond well to standard R-CHOP therapy.

Introduction of Combined CHOP Plus Rituximab Therapy Dramatically Improved Outcome of Diffuse Large B-Cell Lymphoma in British Columbia

2005 ◽  
Vol 23 (22) ◽  
pp. 5027-5033 ◽  
Author(s):  
Laurie H. Sehn ◽  
Jane Donaldson ◽  
Mukesh Chhanabhai ◽  
Catherine Fitzgerald ◽  
Karamjit Gill ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Ratio ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Survival Risk ◽  
Large B Cell

Purpose For more than two decades, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been the standard therapy for diffuse large B-cell lymphoma (DLBCL). The addition of rituximab to CHOP has been shown to improve outcome in elderly patients with DLBCL. We conducted a population-based analysis to assess the impact of this combination therapy on adult patients with DLBCL in the province of British Columbia (BC). Methods We compared outcomes during a 3-year period; 18 months before (prerituximab) and 18 months after (postrituximab) institution of a policy recommending the combination of CHOP and rituximab for all patients with newly diagnosed advanced-stage (stage III or IV or stage I or II with “B” symptoms or bulky [> 10 cm] disease) DLBCL. Results A total of 292 patients were evaluated; 140 in the prerituximab group (median follow-up, 42 months) and 152 in the postrituximab group (median follow-up, 24 months). Both progression-free survival (risk ratio, 0.56; 95% CI, 0.39 to 0.81; P = .002) and overall survival (risk ratio, 0.40; 95% CI, 0.27 to 0.61, P < .0001) were significantly improved in the postrituximab group. After controlling for age and International Prognostic Index score, era of treatment remained a strong independent predictor of progression-free survival (risk ratio, 0.59; 95% CI, 0.41 to 0.85; P = .005) and overall survival (risk ratio, 0.43; 95% CI, 0.29 to 0.66; P < .001). The benefit of treatment in the postrituximab era was present regardless of age. Conclusion The addition of rituximab to CHOP chemotherapy has resulted in a dramatic improvement in outcome for DLBCL patients of all ages in the province of BC.

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