Ultimate Outcomes of Patients with Recurrent Diffuse Large B Cell Lymphoma Who Do Not Respond to Second-Line Chemotherapy

Background: Patients with diffuse large B cell lymphoma (DLBCL) who relapse after or are refractory to initial therapy can in some cases experience long term disease free survival after second-line chemotherapy alone or followed by autologous stem cell transplantation. The major predictor of outcome for patients undergoing autologous transplant is response to prior (second-line) chemotherapy. Patients not responding to second-line regimens may receive third-line or subsequent chemotherapy regimens in hopes of achieving response and proceeding to transplant, but available outcome data from this group have been limited.

Methods: We used pathology and treatment records to identify patients with relapsed or refractory DLBCL (excluding transformed lymphoma) at the Weill Cornell Medical Center for whom data on response to second-line chemotherapy could be determined. An online social security database verified survival. Median overall survival (OS) was calculated by the Kaplan-Meier method.

Results: One hundred eight patients with relapsed or refractory DLBCL who underwent second line chemotherapy were identified, and adequate treatment records were available for 74 of these patients. Chemotherapy consisted of ifosfamide-containing regimens in 60 patients (81%), platinum-containing regimens in 61 (82%) and included rituximab in 29 (39%). Forty-seven patients (64%) achieved at least a partial response (R), while 27 patients (36%) did not respond (NR). Median OS from second therapy was 4 months (range 1–61) in the NR group, and was projected at 66 months (range 2–106) in the R group. Only one patient in the NR group (4%) survived for greater than one year. Twenty-four NR patients underwent third-line therapy, of whom 5 of 19 with available response data achieved a clinical response (5 died prior to response assessment) and 3 underwent autologous transplantation. Two patients progressed within 3 months of transplantation, with OS from transplantation of 4 months, while the third patient is alive in remission at 59 months after transplant. Neither longer duration of first remission (HR 1.00, p=0.85) nor choice of subsequent aggressive chemotherapy over less intensive approaches (HR 0.81, p=0.65) conferred a survival benefit in patients who had not responded to second-line therapy.

Conclusion: Patients with recurrent DLBCL who do not respond to second-line chemotherapy have poor outcomes, with only rare patients achieving extended survival following subsequent chemotherapy. Clinical trials of novel therapeutic regimens should be prioritized as management strategies for these patients.