LY-05. Comparison of toxicity and efficacy of BeEAC, LEAM, and CLV conditioning regimens before autologous stem cell transplantation for treatment of primary-refractory and relapsed forms of Hodgkin’s lymphoma

Summary

High-dose chemotherapy (HDCT) followed by autologous transplantation of hematopoietic stem cells (ASCT) is the gold standard of treatment for patients with primary-refractory and relapsed forms of Hodgkin’s lymphoma (R/R HL). There are several most commonly used conditioning regimens for HDCT followed ASCT. However, there are currently no data on the conduct of randomized studies that would compare the effectiveness and toxicity of different regimens.

Aims

Comparison HDCT (CLV, LEAM, BeEAC) as a conditioning regimen before ASCT for the treatment of R/R HL.

Patients and methods

In retrospective study were included 279 patients with HL, median age 30 years; 121 men and 158 women. All patients received HDCT and ASCT in National Medical and Surgical Center named after N. I. Pirogov (2006-2018). Conditioning regimens: CLV (cyclophosphamide, lomustine, etoposide) – 78 patients, LEAM (lomustine, etoposide, cytarabine, melphalan) – 129 patients, BeEAC (bendamustine, cytarabine, etoposide, cyclophosphamide) – 72 patients.

Results

Efficiency of different conditioning regimens. Comparative analysis of overall survival (OS) showed lower OS rates in patients who received LEAM. 5-year overall survival: CLV – 82%, BeEAC – 78%, LEAM – 70% (p=0.04). 5-year progression-free survival (PFS) were comparable with LEAM (53%), BeEAC (50%) and CLV (50%) (p=0.66). Hematologic toxicity of different regimens (CLV, LEAM, BeEAC): All patients developed grade IV neutropenia, anemia with/without transfusion demands, severe thrombocytopenia with transfusion requirements in most cases. Duration of neutropenia was the same (median of 9 days). Duration of thrombocytopenia in CLV regimen was 9 days, LEAM and BeEAC – 11 days (p=0.03). Anemia Grade II (median) was registered in CLV, Grade III (median) in LEAM and BeEAC regimens (p>0.05). Non-hematologic toxicity was as follows: The incidence of oral mucositis and enteropathy was higher in the BeEAC (40.3%, n=29) and LEAM (56.6%, n=72) regimen compared to the CLV regimen (34.6%, n=27). The development of cardiotoxicity was also more often noted in the BeEAC and LEAM groups, 6.9% and 2.3%, respectively. Indices of liver toxicity, pulmotoxicity and the incidence of infectious complications were comparable. Transplant-related mortality (until D + 30) was: CLV – 1.3%, LEAM – 3.1%, BeEAC – 2.8% (р>0.05). Efficiency of conditioning regimens was assessed as overall survival (OS) and progression-free survival (PFS). Comparative analysis of OS rates showed lower OS values in the patients who received LEAM treatment, with 5-year OS of 82% after CLV, 78% following BeEAC, and 70% after LEAM conditioning (p=0.04). The 5-year progression-free survival rates (PFS) were comparable for the patients treated according to LEAM (53%), BeEAC (50%) and CLV protocols (50%, p=0.66).

Conclusion

HDCT followed by ASCT is the best therapeutic approach for a R/R HL. BeEAC, LEAM and CLV conditioning regimens being considered as viable alternatives. Our results suggest a comparable efficacy of BeEAC, LEAM and CLV conditioning in terms of survival and disease control. However, we also observed higher rates of gastrointestinal and cardiac toxicities in patients transplanted after LEAM and BeEAC. The worst OS in patients received LEAM can be explained by the fact that the regimen was implemented at our hospital earlier than others schedules when such drugs as Brentuximab vedotin and checkpoint inhibitors were not available to the patients with relapse after HDCT and ASCT.

Keywords

Transplantation, AHSCT, conditioning regimens, Hodgkin’s lymphoma, BeEAC, CLV, LEAM.