Outcomes in primary cutaneous diffuse large B-cell lymphoma, leg type.
Authors: Kraft Robert M. , Ansell Stephen M. , Villasboas Jose Caetano , Bennani N. Nora , Wang Yucai , Habermann Thomas Matthew , Thanarajasingam Gita , Inwards David James , Porrata Luis F. , Micallef Ivana N. M. , Witzig Thomas E. , Thompson Carrie A. , Johnston Patrick B. , Nowakowski Grzegorz S. , Lin Yi , Paludo Jonas 
Published: June 2021

e19547

Background: Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is a rare, aggressive lymphoma characterized by skin involvement predominantly in the lower extremities, and is associated with an inferior prognosis compared to other primary cutaneous B-cell lymphomas. Immunochemotherapy with or without involved-field radiation therapy (IFRT) is considered standard, front-line therapy. Interestingly, over-expression of PD-L1/PD-L2 has been shown in a high proportion of PCDLBCL, LT cases, but efficacy of immune checkpoint inhibitors (ICI) in relapsed/refractory, PCDLBCL, LT has not been thoroughly studied. Therefore, we describe the outcomes of 1) immunochemotherapy with and without IFRT as front-line treatment of PCDLBCL, LT, and 2) ICIs in the relapsed/refractory setting. Methods: We conducted a retrospective cohort study of patients diagnosed with PCDLBCL, LT seen at Mayo Clinic from January 1, 2000 to December 31, 2020. Using the Kaplan-Meier method, we calculated progression-free survival (PFS), duration of response (DOR), and overall survival (OS) in patients who received front-line R-CHOP with and without IFRT, and salvage ICI therapy for relapsed/refractory disease. Results: A total of 28 patients with PCDLBCL, LT were identified. The median age at diagnosis was 71.6 years (range 48.0-91.7), 50% (N = 14) were male, and 78.6% (N = 22) had disease involvement of the lower extremities at diagnosis. For front-line treatment, 31.2% (N = 9) received R-CHOP with IFRT, and 31.2% (N = 9) received R-CHOP without IFRT. The median PFS in patients treated with R-CHOP plus IFRT was 41.8 months [95% CI: 30.2-69.6] compared to 13.7 months [95% CI: 10.7-27.7; p= 0.01] in those treated with R-CHOP without IFRT. The median OS in patients treated with R-CHOP plus IFRT was 74.7 months [95% CI: 53.0-108.6] compared to 38.2 months [95% CI: 26.0-80.4; p= 0.14] in those treated with R-CHOP without IFRT. Patient and disease characteristics were similar among these two groups. ICIs were used in 17.9% (N = 5) of patients with relapsed/refractory, PCDLBCL, LT, and these patients had received a median of three (range 2-10) prior systemic therapies. The overall response rate was 60% as three patients treated with ICIs achieved a complete response, and the other two patients showed no clinical response. The median DOR from ICIs was 23.0 months [95% CI: 3.6-26.0]. The median PFS from ICI therapy was 10.2 months [95% CI: 3.6 – not reached]. Only one of the five patients was noted to have a mild side effect from ICI treatment (elevated alkaline phosphatase, grade 1). Conclusions: R-CHOP with IFRT was associated with a longer median PFS compared to R-CHOP without IFRT as front-line therapy for PCDLBCL, LT. Furthermore, ICIs may have a role in treating relapsed/refractory disease as reasonable activity in heavily pre-treated patients and a favorable safety profile were observed in this study. Further studies would be of benefit to confirm our findings.