Clinical efficacy and tolerability of venetoclax plus rituximab in patients with relapsed or refractory chronic lymphocytic leukemia-a real-world analysis of the Polish Adult Leukemia Study Group.

The results of the MURANO trial showed encouraging progression-free survival (PFS) and overall survival (OS) in relapsed/refractory chronic lymphocytic leukemia (RR-CLL) patients treated with venetoclax-rituximab (VEN-R). A retrospective analysis was performed to evaluate the efficacy and safety of VEN-R within the Polish Adult Leukemia Study Group (PALG) centers. The study group included 117 patients with RR-CLL (with early relapse after immunochemotherapy or bearing TP53 aberrations) treated with VEN-R in 2019-2023 outside clinical trials. Patients were treated with a median of 2 (range 1-9) previous lines of therapy. Twenty-two participants were previously treated with BTKi (18.8% out of 117). The median follow-up was 20.3 months (range 0.27-39.1). The overall response rate (ORR) was 95.3% in the group of patients in whom a response to treatment was assessed and 86.3% for all patients. Twenty patients (17.1% out of 117) achieved a complete response (CR), 81 (69.2%) achieved a partial response (PR), and in 5 patients (4.3%), disease progression was noted (assessed as the best response during treatment). The median PFS in the whole cohort was 36.97 (95% CI 24.5, not reached) months, and the median OS was not reached (95% CI 27.03, not reached). Thirty-six patients died during the follow-up, 10 (8.5%; 27.8% of deaths) due to COVID-19 infection. All grade neutropenia (n = 87/117, 74.4%; grade 3 or higher n = 67/117, 57.3%) was the most common treatment adverse event. Forty-five patients (38.5%) remained on treatment, and twenty-two (18.8%) completed 24 months of therapy, while it was discontinued in fifty cases (42.7%). In this real-world setting of early access in very high-risk RR-CLL patients, the VEN-R regimen was associated with shorter median PFS compared with the results of the MURANO trial. This outcome, however, could be attributed to patients' exposure to SARS-CoV-2 infection and the aggressive course of the disease as very high-risk patients, after multiple lines of prior therapies, were included in the Polish Ministry of Health reimbursement program.

Richter transformation - retrospective treatment outcomes analysis in Polish Adult Leukemia Study Group.

Richter transformation (RT) is defined as developing an aggressive lymphoma in 2-10% of patients suffering from chronic lymphocytic leukemia (CLL). So far, no complex analysis of RT demographics and treatment outcomes has been performed in Poland. Thus, the retrospective analysis of 124 patients with RT from Polish hematology centers was designed. Ninety-nine patients with diffuse large B-cell lymphoma (DLBCL-RT) were identified. The median overall survival (OS) for DLBCL-RT was 17.3 months, while for Hodgkin lymphoma (HL-RT)-21.3 months. In multivariate analysis, the independent factors of worse OS for DLBCL-RT were: prior CLL therapy, ECOG stage ≥2, and elevated serum LDH activity. Patients who proceeded to hematopoietic stem cell transplantation (HSCT) achieved better results. The median OS in allogeneic HSCT recipients was not reached, while in autologous HSCT median OS was 51.3 months. In conclusion, our study represents the largest dataset of patients diagnosed with RT in Poland and confirms its dismal prognosis.

Outcome of SARS-CoV-2-Infected Polish Patients with Chronic Lymphocytic Leukemia.

BACKGROUND: The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has become the cause of a worldwide pandemic, and its clinical infection course in patients with hematological malignancies may be severe. METHODS: We performed a retrospective study on 188 chronic lymphocytic leukemia patients (CLL) with COVID-19 infection. RESULTS: At the time of infection 51 patients (27.1%) were treated with Bruton tyrosine kinase inhibitor (BTKi), 46 (24.5%) with anti-CD20 antibodies while 37 patients (19.7%) received venetoclax. In total, 111 patients (59.0%) required hospitalization and 50 patients (26.5%) died due to COVID-19. Patients with poor performance status (ECOG >1; p = 0.02), advanced age (>65 years; p = 0.04), low hemoglobin concentration (≤10 g/dl; p = 0.0001), low platelets (<100 × 109/L; p = 0.003), and elevated lactate dehydrogenase level (LDH; p = 0.014) had an increased risk of death due to COVID-19. Neither CLL treatment status (treatment naïve vs. treated) nor the type of CLL-directed treatment had impact on the SARS-CoV-2 related risk of death. The multivariate survival analysis showed that advanced age (p = 0.009) and low platelet count (p = 0.0001) were associated with significantly shorter patients' overall survival. CONCLUSIONS: SARS-CoV-2 infection in CLL patients is associated with poor outcome regardless of administered CLL-directed treatment.