R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study.

BACKGROUND: The role of re-treatment with rituximab in aggressive B-cell lymphomas still needs to be defined. This study evaluated the influence of prior exposure to rituximab on response rates and survival in patients with diffuse large B-cell lymphoma treated with rituximab plus etoposide, cytarabine, cisplatinum and methylprednisolone (R-ESHAP). DESIGN AND METHODS: We retrospectively analyzed 163 patients with relapsed or refractory diffuse large B-cell lymphoma who received R-ESHAP as salvage therapy with a curative purpose. Patients were divided into two groups according to whether rituximab had been administered (n=94, "R+" group) or not (n=69, "R-" group) prior to R-ESHAP. RESULTS: Response rates were significantly higher in the R- group in the univariate but not in the multivariate analysis. In the analysis restricted to the R+ group, we observed very low complete remission and overall response rates in patients with primary refractory disease (8% and 33%, respectively), as compared to those in patients who were in first partial remission (41% and 86%) or who had relapsed disease (50% and 75%) (p<0.01 in both cases). Overall, 60% and 65% of patients in the R+ and R- groups, respectively, underwent stem-cell transplantation after the salvage therapy. With a median follow-up of 29 months (range, 6-84), patients in the R+ group had significantly worse progression-free survival (17% vs. 57% at 3 years, p<0.0001) and overall survival (38% v 67% at 3 years, p=0.0005) than patients in the R- group. Prior exposure to rituximab was also an independent adverse prognostic factor for both progression-free survival (RR: 2.0; 95% CI: 1.2-3.3, p=0.008) and overall survival (RR: 2.2; 95% CI: 1.3-3.9, p=0.004). CONCLUSIONS: R-ESHAP was associated with a high response rate in patients who were not refractory to upfront rituximab-based chemotherapy. However, the survival outcome was poor for patients previously exposed to rituximab, as compared to in those who had not previously been treated with rituximab.

Brentuximab vedotin in Hodgkin lymphoma and anaplastic large-cell lymphoma: an evidence-based review.

Hodgkin lymphoma (HL) and anaplastic large-cell lymphoma (ALCL) account for ~10% and 2%-3% of all cases of lymphoid neoplasms, respectively. Up to 30% of patients with HL are refractory or relapse after first-line therapy, and elderly patients with HL represent a subgroup of patients with suboptimal responses to the currently available treatments. Five-year overall survival for ALCL patients is 50%-80% with conventional chemotherapy. Therefore, new therapeutic approaches are needed for these groups of patients. Brentuximab vedotin is a chimeric IgG1 anti-CD30 antibody-drug conjugate that has all the features that are necessary to make a substantive difference with the standard therapies in patients with HL and ALCL: a novel mechanism of action, single-agent activity, non-cross-resistance, and safety both in the relapsed-refractory and in the front-line setting. This review provides an update of the results of the most relevant clinical trials including brentuximab vedotin for patients with HL and ALCL conducted to date.

Immunotherapy for the treatment of Hodgkin lymphoma.

INTRODUCTION: Most patients with Hodgkin lymphoma (HL) enjoy durable remissions following front-line treatment but 30% of patients are refractory or relapse after first line therapy. Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) can cure an additional 50-55% of relapsing patients but new treatments are needed for patients with HL who are refractory or relapse after ASCT. Immunotherapy has emerged as a promising treatment for the management of these patients. The availability of the anti-CD30 antibody brentuximab vedotin and new targeted drugs such as immune checkpoint inhibitors, show promising clinical activity in patients with HL and are important milestones for the management of patients with HL particularly for those who have progressed after standard initial therapy and ASCT. Areas covered: Overview of the results from the most relevant clinical trials including monoclonal antibody-based therapy in HL. Phase 2 and phase 3 trials including brentuximab vedotin and immune checkpoints inhibitors in patients with Hodgkin lymphoma have been reviewed. In addition, the potential impact of these new therapies in the management of patients with newly diagnosed HL has also been addressed. Expert commentary: Anti-CD30 antibody brentuximab vedotin and immune checkpoint inhibitors have shown promising results in patients with relapsed and refractory HL. Administration of these therapies earlier in the course of the disease might reduce the proportion of relapsed or refractory patients and, subsequently, minimize the number of patients undergoing high-dose therapy and autologous stem cell transplantation. We have little doubt that this will have substantial effects on the outcome for future generations of HL patients.