Early Failure of Frontline Rituximab-Containing Chemo-immunotherapy in Diffuse Large B Cell Lymphoma Does Not Predict Futility of Autologous Hematopoietic Cell Transplantation

Abstract

The poor prognosis of diffuse large B-cell lymphoma (DLBCL) patients relapsing within 1-year of initial diagnosis after first-line rituximab-based chemoimmunotherapy has created controversy about the role of autologous transplantation (auto-HCT) in this setting. We compared auto-HCT outcomes of chemosensitive DLBCL patients between 2000 and 2011 in two cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1-year of initial diagnosis. The ERF cohort was compared with those relapsing >1-year after initial diagnosis (Late Rituximab Failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Non-relapse mortality (NRM), progression/relapse, progression-free survival (PFS) and overall survival (OS) of ERF vs. LRF cohorts at 3-years were 9% (95%CI 6–13) vs. 9% (95%CI 5–13), 47% (95%CI 41–52) vs. 39% (95%CI 33–46), 44% (95%CI 38–50) vs. 52% (95%CI 45–59) and 50% (95 CI 44–56) vs. 67% (95%CI 60–74), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk (RR) 1.31, p=0.34). ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR 2.08, p<0.001) and overall mortality (RR 3.75, p<0.001) within the first 9 months post auto-HCT. Beyond this period, PFS and OS were not significantly different between ERF and LRF cohorts. Auto-HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS 44%), and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.

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

“…[8][9][10] Even among patients with relapsed or refractory DLBCL who respond to salvage therapy and are able to undergo ASCT, about 50% will ultimately relapse after transplantation. 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.…”

Autologous stem cell transplantation for relapsed/refractory diffuse large B-cell lymphoma: efficacy in the rituximab era and comparison to first allogeneic transplants. A report from the EBMT Lymphoma Working Party

“…This supports previous observations that prior rituximab exposure did not negatively impact the outcome of patients undergoing autoSCT for DLBCL. 22,23 As our database registers only patients who were actually transplanted, this observation does not exclude the possibility that the prognosis of DLBCL failing first-line immunochemotherapy may be worse than for those receiving chemotherapy alone. The current study also confirms previous findings that patients failing to respond to salvage induction and who have relapsed within a year of first-line therapy have a worse outcome following autoSCT.…”

Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second-line salvage regimens in the International CORAL study

“…Thus, bridging to intensification and transplantation can remain a valid strategy, as previously shown for patients responding to second-line treatment. 7,17,18 Allo-SCT could be considered in our study population, and recently an encouraging OS of 47% at 1 year was reported in aggressive lymphoma relapsing o 12 months after last line and treated with lymphomadirected myeloablative conditioning followed by allo-SCT. 19 However, most experts would restrict this option to patients relapsing after ASCT.…”

“…7,8 Still, even in the latter patients with poor prognosis relapses, ASCT remains the standard of care if patients can achieve CR/PR pretransplantation. [9][10][11] We were interested in the characteristics and survival of patients included in the CORAL study, who did not fulfill the protocol strategy at the time of evaluation before transplant. Clinicians had no per-protocol recommendation, except to complete a dedicated form at the time of withdrawal to record what was happening.…”