Mechanism and Treatment of Rituximab Resistance in Diffuse Large Bcell Lymphoma

2019 ◽  
Vol 19 (9) ◽  
pp. 681-687 ◽  
Author(s):  
Linqing Zou ◽  
Guoqi Song ◽  
Siyu Gu ◽  
Lingling Kong ◽  
Shiqi Sun ◽  
...  

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype B non-Hodgkin lymphoma in adults. After rituximab being introduced to treat DLBCL, the current first-line treatment is R-CHOP regimen. This regimen greatly improves patient's prognosis, however, relapsed or refractory cases are commonly seen, mainly due to the resistance to rituximab. Although a large number of experiments have been conducted to investigate rituximab resistance, the exac mechanisms and solutions are still unclear. This review mainly explores the possible mechanisms oft rituximab resistance and current new effective treatments for rituximab resistance in DLBCL.

2020 ◽  
Vol 99 (7) ◽  
pp. 1605-1613
Author(s):  
T. Systchenko ◽  
G. Defossez ◽  
S. Guidez ◽  
C. Laurent ◽  
M. Puyade ◽  
...  

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4878-4878
Author(s):  
Heidi Mocikova ◽  
Jozef Michalka ◽  
Jan Koren ◽  
Pavla Stepankova ◽  
Alexander Wild ◽  
...  

Abstract Abstract 4878 Background. Strong CD20 expression in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) suggests the feasibility of rituximab in the treatment of this disease. Methods. We analysed the outcome of 102 patients with NLPHL treated with or without rituximab in combination with conventional treatment: chemotherapy and/or radiotherapy. Histologies were reviewed for the purpose of this study. Rituximab was administered in 26 of 102 NLPHL patients (13 in the first line treatment and in 13 of 20 relapsed patients). Additionally, rituximab with chemotherapy was administered in 11 patients with histologic transformation to diffuse large-B cell lymphoma. Median follow-up was 7.1 years. Median patient age was 34.2 years. Results. The 10-year overall survival (OS) rate and progression - free survival (PFS) of the whole group was 88% and 65%, respectively. There was no difference in OS and PFS in patients with clinical stage IA without risk factors treated without or with rituximab (30 vs 3 patients) and conventional treatment, however the follow-up in the rituximab group was short. The addition of rituximab to conventional treatment did not affect the OS in the group of patients with more advanced disease: 58 patients without vs 10 with rituximab (94% [95% CI: 88 – 100%] vs 100% [-], P=0.566). PFS in both groups did not differ significantly in the first line treatment (69% [95% CI: 57 – 82%] vs 100% [-], P=0.165), however when all lines of treatment were analysed, PFS was significantly better in patients treated without rituximab (92% [95% CI: 84 – 100%] vs 38% [95% CI: 22 – 65%], P< 0.001). Histologic transformation to diffuse large B - cell lymphoma was diagnosed in 11 rituximab naive patients, but this was not statistically significant when compared to 0 patients after rituximab treatment (14,5% vs 0%, P=0.061). Histologic transformation was the only poor prognostic factor that influenced OS (HR 7.936, P=0.004). Conclusions. Rituximab does not prevent relapses in NLPHL. This study confirms favorable OS of NLPHL patients regardless whether rituximab was used or not. The absence of histologic transformation in NLPHL patients treated with rituximab deserves further investigation. Disclosures: No relevant conflicts of interest to declare.


2017 ◽  
Vol 35 ◽  
pp. 335-336 ◽  
Author(s):  
J. Romejko-Jarosinska ◽  
G. Rymkiewicz ◽  
E. Paszkiewicz-Kozik ◽  
A.P. Dabrowska-Iwanicka ◽  
A. Borawska ◽  
...  

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4440-4440
Author(s):  
Beatrice Casadei ◽  
Alessandro Broccoli ◽  
Vittorio Stefoni ◽  
Cinzia Pellegrini ◽  
Letizia Gandolfi ◽  
...  

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.


2019 ◽  
Vol 60 (14) ◽  
pp. 3375-3385 ◽  
Author(s):  
Myrna Candelaria ◽  
Derlis E. González ◽  
Marcia Torresan Delamain ◽  
Daniel Oscar Bär ◽  
Surender Kumar Beniwal ◽  
...  

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