Utility of immune checkpoint inhibitors (ICI) in 3 patients (pts) with sarcomas of antigen presenting cells (follicular dendritic cell sarcoma [FDCS], histiocytic sarcoma [HS]).

Abstract

e23574 Background: FDCS and HS are rare tumors arising from sustentacular cells of the lymph node, rather than lymphocytes. Surgical resection is often employed in case of localized disease, but for unresectable disease, anthracycline-based therapy is commonly used. PD-L1 staining is reportedly positive in 50-80% of FDCS. As a result, we treated 3 patients (pts) with ICI ipilimumab and nivolumab (Ipi/Nivo), and demonstrated the activity of these agents in these rare cancers. Methods: Two FDCS pts and one HS pt, all with B symptoms at the start of treatment, received Ipi/Nivo in the approved dose/schedule (Table). The HS patient was HIV(+) with undetectable viral load on treatment. One FDCS patient received radiation therapy to an active site of disease during immunotherapy. We reimaged patients every 2 months for the first 6 months, then less frequently. PDL-1 IHC and mutation data were available in all cases. Results: Mutation burden varied from low to intermediate; mutations in kinase genes were also observed. Case 1 (FDCS) demonstrated RECIST 1.1 complete response, but also received radiation, and Case 2 (FDCS) had RECIST partial response. Both continue on treatment 9 months after initiation. Case 3 (HS) demonstrated a minor response to treatment, then disease worsened after 4 months, and he subsequently received radiation to the residual site of disease. All patients showed resolution of B symptoms on ICI. Conclusions: We treated these pts with ICI based on their role as antigen presenting cells, as well as their high PD-L1 expression. We speculate that FDCS and related tumors such as HS represent extreme examples of cancers that have evidence of tertiary lymphoid structures, increasingly recognized as important in ICI responsiveness. Prospective clinical trials of ICI in these diagnoses will help us understand the basis of immune responses to ICI in other cancers. [Table: see text]

Prolonged remission with pembrolizumab and radiation therapy in a patient with multisystem Langerhans cell sarcoma

“…Pembrolizumab or other ICI can be an important therapeutic strategy for these patients who otherwise have a guarded prognosis with limited efficacious options available. A previous report for a patient with HS (PD-L1 expression unknown, TMB intermediate) treated with ipilimumab/nivolumab demonstrated a transient minor response before progression at the 4 month mark, 11 somewhat similar to what occurred in our case. Our patient had a focal disease progression approximately 4-months into pembrolizumab, which responded to radiation therapy and continued to demonstrate ongoing systemic remission with maintenance pembrolizumab.…”

Favorable outcome of a histiocytic sarcoma patient treated with immune checkpoint inhibitor: a case report

“…However, this patient had a heterogenous response to immunotherapy and pathological evaluation of the resistant site showed loss of PD-L1 expression, which suggested a refractory mechanism to immunotherapy. Immunotherapy also showed efficacy in several cases of other sarcomas of antigen presenting cells such as follicular dendritic cell sarcoma and Langerhans cell sarcoma 19 , 20 . Interestingly, Zanwar et al .…”