Introduction: The incidence of HIV-positive lymphoma remains significantly higher than HIV-negative patients in the era of combined antiretroviral therapy(cART). DLBCL is the most common histological type of HIV-positive non-Hodgkin's lymphoma(NHL). Exportin 1 protein(XPO1) inhibitor has demonstrated preliminary anti-HIV activity and synergy with anti-lymphoma drug(e.g. etoposide, doxorubicin, prednisone).

Methods: The study was designed to evaluate safety and efficacy of selinexor (60mg Days 1, 8, 15) combined with R-EPOCH(rituximab 375 mg/m2 d1, etoposide 50 mg/m2 d1-d4, doxorubicin 10mg/m2 d1-d4, vinblastine 0.4mg/m2 d1-d4, prednisone 60mg/m2 d1-d5 and cyclophosphamide 750mg/m2 d5) every 3 weeks (4-6 cycles), followed by selinexor maintenance (60 mg weekly) or transplantation as per physician's choice in patients with newly diagnosed HIV-positive DLBCL. All patients received cART concomitantly during chemotherapy. This study was registered at Chictr.org.cn(ChiCTR2300069941).

Results:From Feb 24, 2023 to Jun 1, 2024, 10 patients were enrolled and received at least two cycles of study treatment. Median age was 47 years (range 40-67) with 8 patients(80%) was male. 9 patients were in advanced stage according to Ann Arbor staging system, and 9 patients with IPI intermediate to high risk. 7 patients(70%) were germinal center B-cell-like lymphoma (GCB) subtype and 8 patients(80%) had an Elevated lactate dehydrogenase level. Median HIV RNA load was 74450(0-1070000) copies/mL and Median CD4 cell count was 182 cells/μL (54-314) with 5 patient having a CD4 cell count less than 200 cells/μL (200 cells/mm3). 4 patients were HBV-positive and 2 was EB virus(EBV) coinfection at baseline.4 patients achieved complete response (CR) after two treatment cycles, and 6 patients achieved partial response (PR) after two cycles therapy. 6 patient of which had completed five or six treatment cycles and all achieved complete response at the end of the treatment cycle. Totally, 6 patients achieved CR, 4 patients achieved PR at the end of treatment cycles. 2 patients after interim evaluation with PR stopped treatment because of loss to follow-up. Patient2 and Patient8 have received autologous hematopoietic stem cell transplantation(ASCT). Patient2 and patient 5 received selinexor maintenance treatment. The EBV DNA load of the patient with EBV coinfection at baseline turned to normal level after two treatment cycle. Similar result was observed in 4 HBV-positive patients, the 3 achieved HBV-negative after two cycles and the other's HBV DNA load level declined from 7.96×10^4 IU/mL to 1.12×10^2 after completing first cycle. HIV RNA load of the patient with CR had declined to <20 copies/mL after the fourth cycle. All patients experienced at least one treatment-emergent adverse event (TEAE), 8 (80%) patients with at least one Grade≥3 TEAE. The most common grade 3 or 4 adverse events were hematological toxicities including neutropenia (80%), thrombocytopenia (40%), anemia (10%). Five patients experienced Febrile neutropenia. The non-hematological toxicities were grade 1 or 2, including fatigue (100%), fever (60%), weight loss(70%), pain (20%), nausea(60%), vomit(50%), constipation(30%), cough(30%). One patient stopped treatment due to central adenovirus infection, pulmonary mycobacterium tuberculosis and influenza A virus infection. All toxicities were manageable by supportive care.

Conclusions: Selinexor plus R-EPOCH regimen demonstrated a favorable Interim efficacy and manageable safety profile in patients with HIV-associated DLBCL. The change of HIV RNA load and CD4+ cell count still requires further evaluation.

Disclosures

No relevant conflicts of interest to declare.

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2024
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