ESHAP with Rituximab Is Highly Efficacious with Durable Responses in Patients with Relapsed/Refractory Aggressive Non-Hodgkin’s Lymphoma.
Authors: Threja Rekha R. , Venugopal Parameswaran , Gregory Stephanie A. , O’Brien Teresa , Bogdanova Elena 
Published: April 2020

Introduction: Patients with relapsed/refractory aggressive non-Hodgkins lymphoma have limited options for further therapy; ESHAP is an active regimen in these patients. Velasquez, et al. reported a 37% complete response and 27% partial response; however, the median duration of survival in this group of patients was 14 months. The addition of rituximab to CHOP improved outcomes in front-line therapy for NHL. Since there is no reported data on the safety and efficacy of ESHAP with rituximab, we have evaluated the combination in patients with relapsed/refractory aggressive lymphoma.

Methods: The regimen consisted of: rituximab (375 mg/m2) given on days 1 and 6, standard ESHAP therapy (etoposide 40 mg/m2 IV/2h day 1–4; methylprednisolone 500 mg/m2 days 1–4; cytarabine 2 g/m2 IV/3h on day 5 and cisplatin 25 mg/m2 CIV days 1–4) on day 8. Rituximab was repeated prior to the third and fifth ESHAP cycle, followed by two additional doses of rituximab after cycle 6 of ESHAP. Cycles were repeated every 21 days. 13 patients enrolled in the study. Median age was 57 years (range 37–70); there were 11 males and 2 females. 10/13 (77%) of patients had advanced disease (stage III/IV). Histology was: Diffuse Large Cell Lymphoma in 12 patients (92%) and Mantle Cell Lymphoma in 1 patient (8%). 9 of 13 patients, according to the IPI, had intermediate or high risk disease. All patients had one or more of the following therapies: CHOP or CHOP-like regimens (with or without radiation therapy), CHOP with rituximab, fludarabine/rituximab or radioimmunotherapy.

Results: Among the 13 patients enrolled, 6 patients completed all 6 cycles. Among these, 4 (66.6%) achieved a CR; 1 PR (16.7%) and 1 PD (16.7%); the overall response rate was 83%. 3 of 4 patients remain in a CR at a median of 48 months (range 46–51 months); 1 pt relapsed after 24 months. The remaining 7 patients received a median of 2 cycles: 1 patient received autologous peripheral blood stem cell transplantation after 3 cycles of therapy with 2.20 x 106/kg CD 34+ cells, 1 patient achieved a CR after 3 cycles for stage 1 disease and remains in a CR at 14 months, 1 patient achieved a CR after two cycles and was lost to follow up, and 1 patient achieved a CR after 3 cycles, however relapsed in five months. 3 patients had PD after cycle 1,1 and 2. 3 of 13 patients had received prior therapy with rituximab; 1 patient achieved a PR and went on to autologous peripheral blood stem cell transplantation, 1 patient achieved a CR of 5 month duration after 3 cycles, and 1 patient had progressive disease. There were five episodes of treatment-related delays in therapy. Two patients required dose reductions. There were three episodes of neutropenic fever.

Conclusion: Without high dose therapy and stem cell transplantation, long term remission in relapsed/refractory aggressive NHL is rare. Our study represents the first reported data on the efficacy and safety of ESHAP and rituximab in this group of patients. This combination therapy leads to durable responses with acceptable toxicity and may be considered as a viable alternative therapy in patients who are not candidates for stem cell transplantation. In addition, after effective cytoreduction with ESHAP and Rituximab, stem cell collection was adequate in our patient who underwent autologous stem cell transplantation.