RESUMEN
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.
RESUMEN
BACKGROUND/AIM: To study the long-term clinical efficacy and tolerability of ibrutinib monotherapy in real-world relapsed and refractory chronic lymphocytic leukemia (RR-CLL) patients outside clinical trials. PATIENTS AND METHODS: Clinical data of 171 RR-CLL patients treated with ibrutinib were collected within the observational study of the Polish Adult Leukemia Study Group. RESULTS: Median patient age was 64 years. Patients were pretreated with 3 (1-10) median lines of therapy, while 42 (24.6%) had 17p deletion. The median observation time was 40 months (range=1-59 months), while median ibrutinib monotherapy reached 37.5 months (range=0.4-59.2 months). Response was noted in 132 (77.2%) patients. The estimated 5-year progression-free survival (PFS) and overall survival (OS) rates were 61.1% (95%CI=49.3-70.9%) and 56.8% (95%CI=45.6-66.6%), respectively. At the time of analysis 97 (56.7%) remained under ibrutinib monotherapy. CONCLUSION: Ibrutinib is clinically effective and tolerable as a monotherapy in real-world RR-CLL patients.
Asunto(s)
Antineoplásicos/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Adenina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Resistencia a Antineoplásicos , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Piperidinas , Polonia , Inhibidores de Proteínas Quinasas/efectos adversos , Pirazoles/efectos adversos , Pirimidinas/efectos adversos , Recurrencia , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: High-dose methylprednisolone (HDMP) with or without anti-CD20 antibody treatment in the pre B-cell receptor inhibitor (BCRi) era was used as potential salvage therapy for relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (r/r CLL/SLL) patients bearing the 17p deletion. PATIENTS AND METHODS: Outcomes were compared in retrospect between r/r patients treated with HDMP (n = 20), ibrutinib (n = 39) and idelalisib with rituximab (n = 14). RESULTS: Higher overall response rates were found in those patients undergoing BCRi therapy compared to HDMP (79.2% vs. 0%; p < 0.0001), along with longer median progression-free survival (not reached vs. 24.1 months; p < 0.01). Nevertheless, there were no differences in the overall survival (HDMP 35.87 months vs. not reached; p = 0.58). CONCLUSION: HDMP treatment was significantly inferior in terms of response rate and progression-free survival in r/r CLL/SLL patients with the 17p deletion, and may only be used whenever novel compounds are unavailable.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-bcr/antagonistas & inhibidores , Terapia Recuperativa , Proteína p53 Supresora de Tumor/genética , Adenina/administración & dosificación , Adenina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Piperidinas/administración & dosificación , Pronóstico , Purinas/administración & dosificación , Quinazolinonas/administración & dosificación , Estudios Retrospectivos , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
BACKGROUND: Development of a novel class of drugs, the B-cell receptor-signaling inhibitors, including ibrutinib, has been a major achievement in the therapy of refractory or relapsed chronic lymphocytic leukemia (CLL). However, the CLL patients who have discontinued the ibrutinib treatment in clinical trials have been reported to have poor prognosis. OBJECTIVES: In this retrospective study by the Polish Adult Leukemia Group (PALG), we analyzed the reasons for ibrutinib cessation and outcomes after discontinuing ibrutinib in refractory or relapsed CLL patients treated in a compassionate use program in Poland. MATERIAL AND METHODS: Polish CLL patients were included if they discontinued ibrutinib for any reason. The clinical data on the course of ibrutinib treatment was collected anonymously using electronic Case Report Forms (CRFs). The causes of discontinuation of ibrutinib as reported by the treating physicians were analyzed. RESULTS: Thirty-seven patients who discontinued ibrutinib were identified. The median duration of ibrutinib treatment in this group was 4.4 months (range: 0.2-25.2). The main reason for discontinuing ibrutinib was adverse events (n = 20, 54%), while 14 (38%) patients discontinued therapy due to disease progression and 3 (8%) due to other causes. The most common treatment complications that led to ibrutinib cessation were severe respiratory tract infections (9 patients, 24%). In the group discontinuing ibrutinib for progressive disease, 11 patients progressed with untransformed CLL, while in 3 patients, a rare type of Richter transformation to Hodgkin's lymphoma was diagnosed. Twenty-nine patients (78%) died during the follow-up period, and median overall survival (OS) reached 2.0 months (95% CI = 0.8-5.5 months). Importantly, no significant survival difference was detected between patients who discontinued ibrutinib due to disease progression and due to adverse events. CONCLUSIONS: The results of this analysis indicate that ibrutinib discontinuation in relapsed or refractory CLL is associated with poor prognosis regardless of the reason for ibrutinib cessation.