Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. It is characterized by the clonal proliferation of mature B cells. The tumor microenvironment (TME) seems to play a crucial role in the survival and proliferation of tumor cells. Multiple new classes of drugs had been approved for the management of patients with CLL, reshaping the treatment paradigm. The most important classes are Bruton’s tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors. Both of them are approved as a first-line treatment in patients with CLL requiring treatment. The role of BTK and BCL-2 in the signaling pathways of the TME is very important. The aim of this review is to summarize the major components of the TME and the available data regarding targeted therapies in CLL.

CD19-targeting chimeric antigen receptor (CAR) T-cells have changed the treatment paradigm of patients with large B-cell lymphoma (LBCL). Three CAR T-cells were approved by the Food and Drug Administration (FDA) for patients with relapsed and/or refractory (R/R) LBCL in the third-line setting: tisagenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel), and lisocabtagene maraleucel (liso-cel), with an ORR ranging from 58% to 82%. More recently, axi-cel and liso-cel were approved as second-line treatments for patients with R/R disease up to 12 months after the completion of first-line chemo-immunotherapy. The safety profile was acceptable with cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome being the two most frequent acute adverse events. Potential long-term toxicities of CD19-targeting CAR T-cells have also been described. Overall, 30% to 40% of patients are cured with a single infusion of CAR T-cells. However, 60% to 70% of patients relapse after being treated with CAR T-cells and have a dismal prognosis. The advent of bispecific antibodies (BsAb) offers an additional treatment modality for patients with R/R LBCL. The aim of this review is to describe the clinical efficacy of the three CAR T-cells, as well as their safety profile. We also compare these three CAR T-cells in terms of their efficacy and safety profile as well as evaluating the place of CAR T-cells and BsAb in the treatment arsenal of patients with R/R LBCL.

Background/Objectives: In Lebanon, the economic crisis since 2019 has severely strained healthcare infrastructure, yet its impact on cancer treatment adherence remains incompletely characterized. This study assessed factors associated with treatment delay and regimen modification to identify barriers to optimal cancer care among Lebanese patients. Methods: This multicenter, cross-sectional study was conducted in five tertiary hospitals in Beirut, Lebanon, between 13 June 2024, and 27 June 2025. Demographic, clinical and treatment data were collected via a structured questionnaire. Bivariate and multivariable binary logistic regression analyses were performed to identify independent predictors of treatment delay (>2 weeks) and incomplete treatment regimens. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) are reported. Results: A total of 244 patients were enrolled in the study. The study population was predominantly female (59.0%) and aged ≥60 years (60.2%). Advanced disease was common, with 50.4% of patients presenting with stage IV disease. Financial vulnerability was widespread: 72.6% reported monthly household incomes below USD 1000, 88.1% reported a decline in income due to the economic crisis, and 39.3% relied on unstable income sources. Overall, 52.5% of patients experienced treatment initiation delays, and 9.0% received incomplete or dose-reduced regimens. On multivariable analysis, reliance on unfixed income independently predicted treatment delay (aOR 2.55, 95% CI 1.42–4.59; p = 0.002), lack of health insurance (aOR 1.91, 95% CI 1.08–3.39; p = 0.026) and pre-treatment surgical costs also increased the odds of delay (aOR 9.03, 95% CI 2.57–31.7; p = 0.001). For incomplete treatment, unfixed income remained an independent predictor (aOR 2.09, 95% CI 1.16–5.79; p = 0.015). A lack of insurance (aOR 5.62, 95% CI 1.22–25.9; p = 0.027) and high laboratory costs (>USD 150 per session) were also associated with incomplete regimens (aOR 1.62, 95% CI 1.02–2.57; p = 0.041). Conclusions: In Lebanon’s crisis context, financial instability was a key factor associated with deviations in cancer treatment. These findings highlight the need for strengthened insurance coverage and subsidization of diagnostic and treatment-related costs to ensure timely and continuous oncologic care.