R-ESHAP as Salvage Therapy for Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: A Spanish GEL-TAMO Multicenter Study.

The addition of Rituximab to CHOP-like chemotherapy (CT) regimens has improved survival in diffuse large B-cell lymphoma (DLBCL). For this reason, Rituximab is also extensively used in combination with salvage CT regimens, although the information published on this setting is scarce. In the present study, we have analysed a large series of patients (pt) treated with R-ESHAP. 151 pt with relapsed or refractory DLBCL received R-ESHAP (Rituximab, etoposide, cytarabine, cisplatinum and methylprednisolone) as salvage therapy between May 2000 and March 2007. Median age was 54 years (19–70). 22% of pt were refractory to front-line therapy, 19% were partial responders, and 56% had relapsed disease. 56% of pt had received Rituximab in addition to CT as first-line treatment. 15 pt had been treated with autologous stem-cell transplantation (ASCT) prior to R-ESHAP. Patients received a median of 3 cycles of R-ESHAP (1–6). Overall response (OR) rate was 72%, with 69 pt (46%) achieving complete response (CR) and 40 (26%) partial response (PR). Factors with significant influence on CR rates in multivariate analysis were: absence of bulky disease (RR: 3.1), PR to first-line treatment (RR: 3.9) or relapsed disease (RR: 5.8), low-risk IPI (RR: 6.6), and administration of ≥3 cycles (RR: 5). Patients who had received Rituximab prior to R-ESHAP had lower CR (39 vs 54%) and OR (66 vs 80%) rates than patients who had not received it, but the difference did not reach statistical significance. In total, 94 out of 151 pt underwent transplantation after the salvage therapy (91 autologous, and 3 allogeneic). With a median follow-up of 22 months (3–73), the 4-year freedom from treatmet failure (FFTF) and overall survival (OS) were 49% and 48%, respectively. Patients who received Rituximab prior to R-ESHAP had a significantly worse FFTF (26 vs 67% at 4 years) and OS (30 vs 63% at 4 years) as compared with patiens who did not receive it. On multivariate analysis, factors significantly associated with a poor OS were: prior exposure to Rituximab (RR: 2.8), high-risk IPI (RR: 5.2), thrombocytopenia <100x10⁹/l at the time of R-ESHAP (RR: 9.5); and achievement of PR (RR: 6.4) or progressive disease (RR: 17) after R-ESHAP. Our results show the efficacy of R-ESHAP prior to ASCT for refractory or relapsed DLBCL. Although prior exposure to Rituximab was associated with a worse outcome, still a significant number of patients responded to the regimen. Future studies are needed in order to determine which patients will benefit from Rituximab re-treatment.