Linperlisib Combined with CHOP Regimen Followed By Autologous Hematopoietic Stem Cell Transplantation and Linperlisib Monotherapy Maintenance for Newly Diagnosed Nodal T-Follicular Helper Cell Lymphoma Patients: A Phase II Trial

Introduction: Nodal T-follicular helper cell lymphomas (nTFHL) are aggressive tumors originating from follicular helper T cells, associated with poor prognosis. For angioimmunoblastic T-cell lymphoma (AITL), the 5-year overall survival (OS) rate is less than 40%, with a progression-free survival (PFS) rate around 20%. Standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens often yield suboptimal outcomes. Linperlisib, a selective PI3Kδ inhibitor, has shown efficacy and a favorable safety profile for peripheral T-cell lymphoma (PTCL) in a phase II trial. This study investigates linperlisib combined with CHOP, followed by autologous hematopoietic stem cell transplantation (HSCT) and linperlisib monotherapy maintenance in newly diagnosed nTFHL patients.

Methods: This single-arm, multicenter phase II study (NCT06347653) enrolled patients aged 18-65 years with histologically confirmed nTFHL, scheduled for autologous HSCT. Histological subtypes included nTFHL-AI (angioimmunoblastic type), nTFHL-F (follicular type), and nTFHL-NOS (not otherwise specified). Patients received linperlisib (80 mg oral QD) combined with CHOP for 6 cycles (21 days each). Patients achieving complete or partial response (CR/PR) after combination therapy underwent autologous HSCT, followed by linperlisib monotherapy maintenance (80 mg oral QD) for 12 cycles (28 days each). Those ineligible for HSCT received linperlisib monotherapy directly. Patients with stable or progressive disease (SD/PD) post-combination therapy were withdrawn from the study. The primary endpoint was PFS, with secondary endpoints mainly including overall response rate (ORR), CR rate at the completion of induction therapy and after transplantation, and stem cell collection success rate.

Results: As of July 8, 2024, 15 patients (median age 61 years, range 48-66; 80% male) were enrolled across 7 clinical centers in China. Subtypes included nTFHL-AI (86.67%), nTFHL-F (6.67%), and nTFHL-NOS (6.67%). Eastern Cooperative Oncology Group (ECOG) performance status scores were 0-1 in 86.67% of patients. Disease staging included 40% at stage II, 13.33% at stage III, and 46.67% at stage IV. All patients completed at least 2 cycles of induction therapy, with 14 patients evaluable for efficacy. Median follow-up was 85 days. The ORR was 100% (14/14), with a CR rate of 78.57% (11/14) and PR rate of 21.43% (3/14). Median time to CR was 43.5 days. Three patients completed 6 cycles of induction therapy with CR, and one patient completed HSCT. Treatment-related adverse events (TRAEs) were reported in all patients, with neutropenia (73.33%) and leukopenia (66.67%) being the most common, followed by fever, nausea, and vomiting (26.67% each). Two patients (13.33%) developed pneumocystis jirovecii pneumonia during the treatment. Grade ≥3 TRAEs were reported in six patients (40%), with the most common being leukopenia (33.33%) and neutropenia (33.33%), followed by thrombocytopenia (6.67%). Treatment interruptions or CHOP regimen dose reductions due to TRAEs occurred in 6.67% (1/15) and 13.33% (2/15) of patients, respectively. Treatment discontinuations due to TRAEs occurred in 13.33% (2/15) of patients.

Conclusion: Linperlisib combined with CHOP shows promising efficacy and manageable safety in newly diagnosed nTFHL patients. This study is ongoing, and further long-term data are anticipated.

No relevant conflicts of interest to declare.