RESUMO
Background: The introduction of venetoclax into clinical practice has improved the outcome of patients with relapsed/refractory chronic lymphocytic leukemia (RR-CLL). The results of the MURANO trial published in March 2018 showed significantly longer progression-free survival (PFS) and overall survival (OS) in RR-CLL patients treated with venetoclax and rituximab (VEN-R) comparing to bendamustine and rituximab (BR) and resulted in the approval of VEN-R in the therapy of RR-CLL in the European Union and the United States. It should be noted that the results of registration studies often do not correspond with the data from real-life observations. Aims: To study the clinical efficacy and safety profile of VEN-R treatment in RR-CLL patients outside clinical trials. Methods: We performed retrospective analysis of RR-CLL patients treated with VEN-R in hematology centers of the Polish Adult Leukemia Study Group (PALG) from 2019 to 2021. Results: Clinical data of 117 RR-CLL patients treated with VEN-R were collected. Median patient age upon initiation of VEN-R therapy was 67 years (range 33 - 84 years). Seventy-two patients (61.5%) were men. Median Cumulative Illness Rating Scale (CIRS) was 6 (range 2 -16). Patients were treated with a median of 2 (range 1-9) previous lines of therapy, whereas 32 patients (27.4%) had relapsed following the first line of treatment. Overall, 25 patients (21.4%) had 17p deletion, whereas TP53 mutation was identified in 13 patients (11.1%). The median follow-up was 9.96 months (range 0.27 -29.13). The overall response rate (ORR) was 95.2%. Seventeen patients (14.5%) achieved complete remission (CR), 83 (70.9%) partial remission (PR), while in 5 patients (4.3%) disease progression was noted. In the patients with 17p deletion (n=22) or TP53 mutation (n=11), CR and PR were observed in 4 (12.1%) and 29 (87.9%) patients, respectively. The median PFS in the whole cohort was 20.8 (95% CI 18.43 -not reached) months and the median OS was not reached. In our study none of the analyzed clinico-pathological factors had significant impact on ORR, PFS and OS. During the follow-up time four (3.4%) cases of Richter transformation were diagnosed. There were 18 deaths recorded during the course of observation;3 (16.7%) due to disease progression and 7 (38.9%) due to COVID-19 infection. The others were due to infections other than SARS-CoV-2 (n=3, 16.7%) and the cause of death could not be specified in five cases (27.8%). Eighty-three patients (70.9%) remain on treatment, while treatment was discontinued in thirty-four cases (29.1%). Reasons for therapy discontinuation included patient's death (52.9%), treatment-related cytopenias (17.6%), disease progression (14.7%), Richter's transformation (11.8%), autoimmune hemolytic anemia (5.9%), diarrhea (2.9%) and infections (8.8%). In one case treatment discontinuation was due to consent withdrawal and one patient was lost to follow-up. The following adverse events of VEN-R treatment were reported during the study: all grade neutropenia (71.8% with grade 3/4 in 55.6%), anemia (51.3%), thrombocytopenia (47%), pneumonia (9.4%), neutropenic fever (6.8%), autoimmune hemolytic anemia (4.3%), immune thrombocytopenic purpura (1.7%), diarrhea (4.3%) and in one case exacerbation of heart failure was observed. Summary/Conclusion: In this retrospective analysis the outcomes of treatment with the VEN-R regimen in real-life setting were worse than those reported in the MURANO trial.
RESUMO
Introduction: The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has become the cause of a worldwide pandemic. The clinical course of COVID-19 was reported to be more severe in patients with cancer, especially with hematological malignancies. Due to the impairment of the immune system, infections are the leading cause of death in patients with chronic lymphocytic leukemia (CLL). Methods: We performed an observational, retrospective study in polish hematological centers within the Polish Adult Leukemia Study Group analyzing the clinical course of SARSCoV- 2 infection in patients with CLL. Results and conclusions: The study group included 188 patients. The median age of the patients was 67.9 years (range 36-87) and 70 (37.2%) were men. The Median Eastern Cooperative Study Group (ECOG) score was 1 (range 0-4). At the time of SARS-CoV-2 infection, 29 (15.4%) patients were treatment-naïve, 41 (21.8%) have ended the treatment, whereas 118 (62.8%) were during the active phase of CLL therapy. The median number of lines of previous treatment regimens was 1 (range 0-7), whereas 24 (12.8%) patients received four or more treatment regimens. At the time of infection 51 patients (27.1%) were treated with Bruton's tyrosine kinase inhibitor (iBTK), 46 (24.5%) with anti-CD20 antibodies while 37 patients (19.7%) were during venetoclax therapy. In the analyzed cohort 111 patients (59.0%) required hospitalization and 50 patients (26.5%) died due to COVID- 19. Patients with poor performance status (ECOG >1), advanced age (≥65 years), low platelet count (<100 G/l), low hemoglobin levels (<10 g/dl), and elevated lactate dehydrogenase (LDH) were at increased risk of death due to SARSCoV- 2 infection. Poor performance status, low platelet count and hemoglobin levels, elevated LDH and advanced Binet stage at diagnosis were associated with the need for hospitalization for the purpose of COVID-19 treatment. Multivariate analysis revealed that independent factors associated with risk of hospitalization due to SARS-CoV-2 infection and its complications were presence of 17p deletion (p = 0.042), anti- CD20 antibody treatment (p = 0.01), low hemoglobin (p = 0.008) and platelet (p = 0.004) levels and elevated LDH (p = 0.0023). Interestingly, the CLL treatment status (treatment naïve vs. treated) or type of administered treatment (BTKi, anti-CD20, or venetoclax) had no impact on SARS-CoV-2 related risk of death. Univariate survival analysis showed that poor performance status (p = 0.02), advanced age (p = 0.04), low platelet count (p = 0.0012), low hemoglobin level (p = 0.0017) and elevated lactate dehydrogenase (p = 0.008) were associated with significantly shorter overall survival. Multivariate Cox regression analysis showed that only the low platelet count (p < 0.0001) and advanced age (p = 0.019) were associated with patients' shorter overall survival. Considering the abovementioned data, SARS-CoV-2 infection in patients with CLL is associated with the poor outcome regardless of administered CLL-directed treatment.