Outcomes of patients with relapsed/refractory diffuse large B‐cell lymphoma with progression of lymphoma after autologous stem cell transplantation in the rituximab era

Abstract

Salvage chemotherapy followed by autologous stem cell transplant (ASCT) remains the current standard of care for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) with chemosensitive disease. The addition of rituximab results in improved overall survival (OS) after first-line treatment, but cure rates of salvage therapy with ASCT are inferior when compared to historical controls. Historically, patients with DLBCL with disease progression following ASCT have had an extremely poor prognosis with a median OS of 3 months. However, there are little data regarding outcomes in the rituximab era. We performed a retrospective study of 56 patients with relapsed or refractory DLBCL with prior exposure to rituximab who had disease progression following ASCT. The median OS from progression following ASCT for the cohort was 9.9 months (95% CI: 5.3-13.1 months). Patients who progressed less than 1 year from ASCT had a significantly shorter OS than those who progressed at 1 year or greater from ASCT (8.2 vs. 26.7 months, P 5 0.01). Patients with at least stable disease following ASCT had a longer OS than those who progressed immediately after ASCT (12.3 vs. 5.3 months, P 5 0.01). Other factors associated with OS were International Prognostic Index (IPI) (P 5 0.01) and LDH level (P 5 0.0003) at the time of progression following ASCT. In the rituximab era, the prognosis for patients with disease progression following ASCT remains poor, but is improved when compared with historical controls. Ultimately, more work needs to be done to develop novel therapeutic strategies tailored to individual patients in this heterogeneous population. Am. J. Hematol. 88:890-894, 2013. V C 2013 Wiley Periodicals, Inc. IntroductionDiffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL) in the United States, accounting for 30% of cases [1]. The addition of the anti-CD20 monoclonal antibody rituximab to first-line cytotoxic chemotherapy results in improved outcomes in patients with newly diagnosed DLBCL [2-6]. However, one-third of patients have disease that relapses after initial therapy or is refractory to initial treatment [4].The standard of care for relapsed or refractory DLBCL is salvage chemotherapy followed by autologous stem cell transplantation for patients with chemosensitive disease. This strategy is based on results of the PARMA trial, which showed that consolidation with ASCT is superior to chemotherapy alone. This pivotal trial was conducted prior to the routine use of rituximab. The overall response to salvage chemotherapy was 58% and the 5 year event-free survival (EFS) was 46% in the ASCT group and 12% in the group receiving chemotherapy without ASCT [7]. In the current era of using rituximab during first-line therapy, the outcomes of salvage treatments are worse for patients with relapsed and refractory DLBCL. The overall response rate to salvage chemotherapy in the more recent CORAL (Collaborative Trial in Relapsed Aggressive Lymphoma) study was 51%, with 3 year EFS after ASCT of ...

Outcomes of diffuse large B-cell lymphoma patients relapsing after autologous stem cell transplantation: an analysis of patients included in the CORAL study

“…The OS of the entire population was 10 months, similar to that reported by Nagle et al 4 (9.9 months) in a retrospective analysis of 56 patients with disease progression after ASCT. Although limited, this OS appears to be better than initially reported in the prerituximab era (3 months).…”

“…The time to progression following ASCT has been identified as a factor impacting OS in previous reports in similar patients. 4,11 Our results thus indicate that in selected DLBCL patients relapsing after ASCT, potentially on the basis of these latter characteristics, implementing a classical strategy with third-line salvage chemotherapy and attempting to achieve a response could remain a valid option, especially when an immune consolidation with allogeneic transplantation is possible. Conversely, patients with post-ASCT relapse bearing high/ 6 12 18 24 30 36 42 48 54 60 22 22 19 15 13 11 5 3 2 1 0 9 6 4 3 2 2 1 1 0 34 18 3 2 2 1 1 0 Survival probability Figure 6.…”

“…There are few registry data in the rituximab era for relapse post ASCT, with a reported median overall survival (OS) of 9.9 months in rituximab-pretreated patients. 4 The CORAL study provided a unique opportunity to look at 75 patients who relapsed after BEAM/ASCT and to shed more light on the outcome and prognostic factors in this population who had an initial response to first salvage treatment.…”

Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study

“…11,12 The prognosis for these patients is poor, especially for those who have high-risk factors such as secondary IPI score .2 or relapse #12 months post-ASCT. 10,13 Thus, most patients with refractory DLBCL have no curative treatment options.…”

“…13 Previous studies of patients with refractory DLBCL included small cohorts of patients. 13,[15][16][17] Despite the clinical awareness of poor outcomes in patients with refractory disease, there has never been a large-scale effort to specifically characterize response to therapy and survival outcomes in these patients. Results from clinical trials and retrospective cohort analyses identified by using a similar definition of refractory showed that these patients have consistently poor clinical outcomes.…”