Safety and Efficacy of Pharmacotherapy Containing the Second-Generation Integrase Inhibitors and Chemotherapy Drugs in AIDS-Related Diffuse Large B-Cell Lymphoma: A Single-Center Retrospective Analysis.

Introduction: Previous research indicates that combining antiviral and anti-tumor drugs may lead to compounded toxic side effects and risks of drug-drug interactions. Our study aimed to investigate the safety and effectiveness of pharmacotherapy combining second-generation integrase inhibitors (INSTIs) with chemotherapy drugs in patients with AIDS-related diffuse large B-cell lymphoma (AR-DLBCL).

Methods: We conducted a retrospective cohort study of newly diagnosed AR-DLBCL patients at the Public Health Clinical Center of Chengdu from February 2020 to May 2023. All patients received a second-generation INSTI-based regimen alongside chemotherapy. Primary endpoints included the frequency and severity of adverse effects (AEs), while secondary endpoints encompassed CD4 count, CD4/CD8 ratio, HIV viral load, and complete response (CR), partial response (PR), and overall response rate (ORR) at the end of treatment. Evaluations were performed at each chemotherapy cycle, with AEs assessed using Common Terminology Criteria for Adverse Events, version 4.02.

Results: We enrolled 96 AR-DLBCL patients with a median follow-up of 15.5 months (range: 5-33). Of these patients, 60 received bictegravir/tenofovir alafenamide/emtricitabine, while 36 were treated with dolutegravir/lamivudine/albuvirtide as their antiretroviral therapy regimen. Regarding chemotherapy, 75 patients underwent R±CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), while 21 received R±EPOCH (rituximab, etoposide, doxorubicin, vincristine, cyclophosphamide, and prednisone). The most common grade 3 or higher AEs during treatment were neutropenia (32.29%) and thrombocytopenia (20.83%). Seven patients experienced serious complications during treatment, including pulmonary tuberculosis (2), multiple organ dysfunction (1), intracranial infection (1), renal failure (1), and severe COVID-19 (2), resulting in 3 deaths. CD4 count and CD4/CD8 ratio showed slight decreases from baseline (251.76 ± 188.53 cells/μL and 0.71 ± 0.69, respectively) to the 6th month (233.44 ± 140.53 cells/μL and 0.66 ± 0.55, respectively), with no statistical significance observed (p = 0.375 and p = 0.608). Viral load rebound was not observed. The objective response rate was 85.41%, with a CR rate of 51.04%. As of June 2024, 15 patients had died from severe infections or progressive disease.

Conclusion: Second-generation INSTIs seem to be a safe and effective first-line treatment option for AR-DLBCL patients undergoing chemotherapy, regardless of the chemotherapy type.