Retreatment with rituximab in 178 patients with relapsed and refractory B-cell lymphomas: a single institution case control study

The role of rituximab retreatment in relapsed B-cell lymphoma is not well known. We undertook a single center retrospective cohort study to investigate the efficacy of retreatment with rituximab with or without chemotherapy in patients with relapsed and refractory B-cell lymphomas. We only included patients treated first-line and in first progression; 178 patients were included in the study, of whom 29% had diffuse large B-cell lymphoma (DLBCL) and 28% had follicular lymphoma (FL). The overall response rate for the first treatment was 81% and for the second treatment was 66%. The median progression-free survival (PFS) for all patients from diagnosis was 13.2 months and from relapse was 12.5 months (not statistically different). For DLBCL the median PFS from diagnosis was 9.6 months and from relapse was 8.4 months, and for FL the median PFS from diagnosis was 26.4 months and from relapse was 19.2 months (not statistically different). The 5-year overall survival was 57%. In a historical comparison with rituximab-naive patients, rituximab-retreated patients had a shorter time to initial relapse than control patients, but there was no difference between the two groups for PFS from relapse. In conclusion, retreatment with rituximab, with or without chemotherapy, yields a high overall response rate in patients with relapsed and refractory B-cell lymphomas. Relapse occurring after rituximab-containing therapy appears to be more aggressive than that occurring after chemotherapy alone. The outcome of retreatment, in terms of progression-free survival, is similar to that of primary treatment

Retreatment with rituximab in 178 patients with relapsed and refractory B-cell lymphomas: A single institution case control study

The role of rituximab retreatment in relapsed B-cell lymphoma is not well known. We undertook a single center retrospective cohort study to investigate the efficacy of retreatment with rituximab with or without chemotherapy in patients with relapsed and refractory B-cell lymphomas. We only included patients treated first-line and in first progression; 178 patients were included in the study, of whom 29 had diffuse large B-cell lymphoma (DLBCL) and 28 had follicular lymphoma (FL). The overall response rate for the first treatment was 81 and for the second treatment was 66. The median progression-free survival (PFS) for all patients from diagnosis was 13.2 months and from relapse was 12.5 months (not statistically different). For DLBCL the median PFS from diagnosis was 9.6 months and from relapse was 8.4 months, and for FL the median PFS from diagnosis was 26.4 months and from relapse was 19.2 months (not statistically different). The 5-year overall survival was 57. In a historical comparison with rituximab-naive patients, rituximab-retreated patients had a shorter time to initial relapse than control patients, but there was no difference between the two groups for PFS from relapse. In conclusion, retreatment with rituximab, with or without chemotherapy, yields a high overall response rate in patients with relapsed and refractory B-cell lymphomas. Relapse occurring after rituximab-containing therapy appears to be more aggressive than that occurring after chemotherapy alone. The outcome of retreatment, in terms of progression-free survival, is similar to that of primary treatment

Early stage follicular lymphoma: What is the clinical impact of the first-line treatment strategy?

Background: Less than 20% of patients with follicular lymphoma (FL) present with Ann Arbor Stage I or II disease at diagnosis. Numerous therapeutic options exist, however radiation therapy is considered the standard of care for early-stage disease based on single-institution or retrospective series. Our aim was to revisit the outcome of patients with localized FL in the rituximab era. Patients and Methods. We analyzed the characteristics and outcomes of 145 early-stage FL patients, who were retrospectively divided into six groups according to their initial treatment: watchful waiting (WW), chemotherapy alone (CT), radiotherapy alone (RT), combined radiotherapy and chemotherapy (RT-CT), rituximab alone (Ri), and immunochemotherapy (Ri-CT). Results: Of the 145 patients, 84 (57.9%) had stage I disease and 61 (42.1%) stage II. The complete response (CR) rate varied from 57% for the Ri group to 95% for the RT-CT group. Overall survival (OS) at 7.5 y of patients treated after 2000 was better than that of those treated prior to 2000. OS did not significantly differ from one treatment to another. In contrast, a significant difference was found for progression-free survival (PFS) at 7.5 y, which favored Ri-CT (60%) therapy versus the others (p=0.00135). Conclusion: Delayed therapy initiation was associated with a similar OS than that observed in patients receiving immediate intervention. The "watchful waiting" strategy may thus be proposed as first-line therapy, similar to stage III and IV FL patients with a low tumor burden. However, when treatment is required, immunochemotherapy appears to be the best option. © 2013 Michallet et al.; licensee BioMed Central Ltd

HLA-DR expression on monocytes and outcome of anti-CD19 CAR T-cell therapy for large B-cell lymphoma

Abstract Despite their unprecedented success in relapsed/refractory (R/R) large B-cell lymphoma (LBCL), anti-CD19 CAR T cells are associated with significant toxicity, and more than half of patients relapse. As monocytes emerged as key players in CAR therapy, we sought to evaluate the evolution of HLA-DR expression on monocytes (mHLA-DR) before and after commercial anti-CD19 CAR T-cell infusion in a large cohort (n = 103) of patients with R/R LBCL and its association with adverse events and treatment response. Cy-Flu-based lymphodepletion (LD) upregulated mHLA-DR in 79% of the cases, whereas in 2l% of cases (15 patients), the mHLA-DR level decreased after LD, and this decrease was associated with poorer outcome. Low mHLA-DR at day minus 7 (D−7) (<13 500 antibodies per cell) before CAR T-cell infusion correlated with older age, poorer performance status, higher tumor burden, and elevated inflammatory markers. With a median follow-up of 7.4 months, patients with low mHLA-DR D−7 exhibited a poorer duration of response and survival than the higher mHLA-DR D−7 group. For toxicity management, tocilizumab was more frequently used in the low–mHLA-DR D−7 group. These data suggest that monocyte dysregulation before LD, characterized by the downregulation of mHLA-DR, correlates with an inflammatory and immunosuppressive tumor environment and is associated with failure of anti-CD19 CAR T cells in patients with R/R LBCL. Modulation of these myeloid cells represents a promising field for improving CAR therapy

Clinicopathological features and survival in EBV-positive diffuse large B-cell lymphoma not otherwise specified

International audienceAbstract In this retrospective study, we report 70 cases of Epstein-Barr virus (EBV)+ diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS) among 1696 DLBCL-NOS cases diagnosed between 2006 and 2019 (prevalence of 4.1%). At diagnosis, median age was 68.5 years; 79% of the cases presented with an advanced-stage disease (III-IV), 48% with extranodal lesions, and 14% with an hemophagocytic lymphohistiocytosis (HLH) (8 at diagnosis and 1 on therapy). A total of 46 cases presented a polymorphic pattern, and 21 were monomorphic. All had a non-germinal center B phenotype, with the majority of tumor cells expressing CD30 and programmed death ligand 1 (98% and 95%, respectively). Type II and III EBV latency was seen in 88% and 12% of the cases, respectively. Patients were treated with immunochemotherapy (59%) or chemotherapy (22%), and 19% received palliative care due to advanced age and altered performance status. After a median follow-up of 48 months, progression-free survival (PFS) and overall survival (OS) at 5 years were 52.7% and 54.8%, respectively. Older age (>50 years) and HLH were associated with shorter PFS and OS in multivariate analysis (PFS: hazard ratio [HR], 14.01; 95% confidence interval [CI], 2.34-83.97; and HR, 5.78; 95% CI, 2.35-14.23; OS: HR, 12.41; 95% CI, 1.65-93.53; and HR, 6.09; 95% CI, 2.42-15.30, respectively). Finally, using a control cohort of 425 EBV− DLBCL-NOS, EBV positivity was associated with a shorter OS outcome within patients >50 years (5-year OS, 53% [95% CI, 38.2-74] vs 60.8% [95% CI, 55.4-69.3], P = .038), but not in younger patients