Selinexor Combined With R-CHOP Achieved a High Response Rate in Newly Diagnosed Double/Triple Hit Lymphoma

Area of Science:

• Hematology
• Oncology
• Clinical Trials

Background:

• Double-hit or triple-hit lymphoma (DH/THL) is an aggressive hematologic malignancy with a poor prognosis.
• Limited effective first-line treatment options exist for DH/THL, necessitating novel therapeutic strategies.

Purpose of the Study:

• To evaluate the efficacy and safety of selinexor combined with R-CHOP (S-RCHOP) as a first-line therapy for patients with newly diagnosed DH/THL.
• To assess secondary endpoints including progression-free survival (PFS), overall survival (OS), and central nervous system (CNS) relapse rates.

Main Methods:

• A single-arm, prospective phase II clinical trial (NCT05974085) enrolled 13 patients with newly diagnosed DH/THL.
• Patients received up to six 21-day cycles of S-RCHOP, with selinexor administered on days 1, 8, and 15.
• Exploratory analyses included next-generation sequencing (NGS) and circulating cell-free DNA (cfDNA) monitoring.

Main Results:

• The overall response rate (ORR) was 100%, with 76.9% achieving complete remission (CR) and 23.1% achieving partial remission (PR).
• At a median follow-up of 25.4 months, the 2-year PFS and OS were 67.7% and 67.1%, respectively.
• Common adverse events included leukopenia/neutropenia (55.1%), febrile neutropenia and fatigue (43.5%), and thrombocytopenia (33.7%).

Conclusions:

• S-RCHOP demonstrates high efficacy in newly diagnosed DH/THL, achieving a 100% ORR.
• The treatment regimen was associated with frequent hematologic adverse events, suggesting a need for dose optimization.
• cfDNA monitoring proved valuable in assessing treatment response, with negativity achieved in 72.7% of patients in CR.