T CELL/HISTIOCYTE-RICH LARGE B-CELL LYMPHOMA: CLINICO-PATHOLOGICAL FEATURES AND RESPONSE TO IMMUNE CHECKPOINT INHIBITORS

T-cell/histiocyte-rich large B-cell Lymphoma (THRLBCL) is an uncommon variant of diffuse large B cell lymphoma (DLBCL), char- acterized by extensive immune infiltrate composed of T-cells and histiocytes; these features excluded THRLBCL by most clinical trials with CarT-cell, creating a strong need for different salvage therapies in this DLBCL variant. We retrospectively reviewed all cases of DLBCL, NOS, treated with curative intent, who were diagnosed in our Institution between Jan 2010-Jan 2022, and we selected patients with THRLBCL morphological features. Diagnostic specimens of THRLBCL were reviewed for the pur- pose of this study. Furthermore, we report of a pilot study conducted at our Institution on 7 patients with THRLBCL, that were relapsed or refractory (R/R) after more than 2 lines of conventional im- munochemotheraphy, that were treated off-label with the immune check point inhibitor pembrolizumab. Of 324 patients with DLBCL, NOS diagnosed at our Institution between 2010 and 2022, 27 (8%) were THRLBCL. No difference between DLBCL, NOS and THRL- BCL was observed in terms of clinical characteristics, type of induc- tion therapy, rate of complete response (CR, 76% and 85%, respectively, p=0.13), progression-free survival (PFS, p=0.72), or overall survival (OS, p=0,20). Of note, THRLBCL were more fre- quently non-GCB by Hans algorithm (78% vs 47%, p=0.002), EBER+ (36% vs 4%, p<0.0001) and CD30+ (56% vs 22%, p=0.0007) than DLBCL, NOS. Seven patients with THRLBCL were treated with pembrolizumab 200 mg, every 3 weeks. All of them were R/R and had received a median of 2 prior therapies (2-5), and all had no available alternative therapeutic options. Median duration of treatment with pembrolizumab was 7 months (range 1-25). Overall response was 71% (all CR), with two patients that are still on active treatment. Median PFS was not reached (Figure 1). Only one patient who had achieved CR relapsed during treatment. Pembrolizumab was well tolerated overall, with only one patient that interrupted after 3 doses due to autoimmune hemolytic anemia. In conclusion, we re- port a monocentric series of patients affected by THRLBCL, showing that these patients have similar clinical characteristics of DLBCL, NOS. We also show, in a pilot setting, that patients with THRLBCL, who are not readily candidate to CarT-cell therapy, may benefit of treatment with checkpoint inhibitors.