Clinical Features and Outcomes of Patients with T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: A Single-Center Analysis

Introduction: T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare subtype of diffuse large B-cell lymphoma characterized by unique pathobiologic features and historically poor outcomes. Recent evidence presented at ASH suggests that intensive first-line (1L) therapy such as alternating R-CHOP/R-ICE or R-EPOCH may improve disease control (Robin ET et al, 2020; Nair R et al, 2021). There are limited data describing outcomes for patients with relapsed THRLBCL treated with autologous stem cell transplant (ASCT) and chimeric antigen receptor T-cell therapy (CAR-T). The optimal treatment for patients with this disease remains unclear.

Methods: We conducted a single-center, retrospective analysis of patients (pts) diagnosed with THRLBCL treated at Emory Winship Cancer Institute between January 2000 and December 2023. Pt characteristics, pathology results, treatment regimens used, and clinical outcomes were abstracted. Univariate models were assessed for significance using chi-square tests and t-tests. Overall survival (OS) was defined as the time from diagnosis to last follow-up or death. Progression-free survival (PFS) was defined as the time from treatment initiation to relapse, death, or last follow-up. Survival curves were estimated using the Kaplan-Meier method.

Results: 71 THRLBCL cases were identified. All had central pathology review at Emory. Twenty-one pts were excluded due to lack of baseline characteristics and follow-up data, resulting in a total of 50 pts included for analysis. Thirty pts (60%) were male. Median age at diagnosis was 45 years (range 19-77 yrs). Twenty-six (52%) self-reported black race/ethnicity. Thirty-one pts (62%) had stage IV disease, 30 (60%) had extranodal involvement, and 18 (36%) had > 2 extranodal sites of disease. Nine pts (18%) were previously diagnosed with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) at a median of 4 yrs (range 0.8-11.8 yrs) before THRLBCL diagnosis, and 8 pts (16%) were diagnosed concurrently with NLPHL and THRLBCL. Univariable analysis did not reveal any significant associations between patient sex, race/ethnicity, stage, number of extranodal sites, disease bulk, or history of NLPHL and OS.

1L therapy consisted of CHOP-based chemo in 44 pts (88%; includes CHOP n=2, R-CHOP n=39, R-pola-CHP n=3) and intensified chemotherapy in 6 (12%). Two pts received ASCT in first remission for THRLBCL; both had prior anthracycline-based treatment for NLPHL. Thirty-four pts (68%) achieved CR after 1L therapy, 13 of whom ultimately relapsed. Thirteen pts (26%) had primary refractory disease. At a median follow-up of 4.3 yrs (range 0.1-22.1 yrs), 3-yr PFS after 1L therapy was 45% and OS was 79% in the entire cohort.

Twenty-six pts (52%) relapsed, 25 of whom received second line (2L) therapy. Seventeen (34%) had early relapses, occurring within 1yr of completing 1L therapy. 2L therapies included platinum-based salvage chemo + ASCT (n=17), platinum-based chemo without transplant (n=5), radiation alone (n=2), and CAR-T (n=1). Eleven of 17 patients with early relapse received ASCT in 2L; all achieved CR with platinum-based salvage prior to transplant, and only 4 relapsed after ASCT. 3-yr PFS from initiation of 2L therapy was 80%. Early relapse was not associated with a significant difference in PFS2 or OS.

Four patients received CAR-T either as 2L therapy (n=1, an early relapser) or > 3L (n=3). Two patients who both received CAR-T as > 3L therapy achieved sustained CR with at least 1 yr follow-up; the other two had PD.

Of note, 15 (30%) pts had persistent FDG-avid adenopathy at completion of 1L or 2L therapy who ultimately did not have relapsed THRLBCL; 11 had biopsies showing benign processes, including follicular hyperplasia and granulomatous inflammation, and 4 had serial imaging showing stability or resolution of adenopathy.

Conclusion: THRLBCL pts in our cohort treated with CHOP-based therapy had a 3-yr PFS of 44% which is inferior compared to expected outcomes of DLBCL treated with R-CHOP. However, relapsed patients receiving 2L platinum-based salvage therapy and ASCT and had favorable outcomes, even among pts relapsing within 1 yr of 1L therapy. False-positive end-of-treatment PET scans were common, highlighting the need for biopsy to confirm relapse before starting additional therapy for this disease. Larger studies are needed to define the optimal 1L therapy for THRLBCL as well as of the use of ASCT vs. CAR-T.