COVID-19 in patients with chronic lymphocytic leukemia: a multicenter analysis by the Czech CLL study group.

Patients with chronic lymphocytic leukemia (CLL) have a high risk of poor outcomes related to coronavirus disease 2019 (COVID-19). This multicenter cohort study evaluated the impact of COVID-19 infection on the population of CLL patients in the Czech Republic. Between March 2020 and May 2021, 341 patients (237 males) with CLL and COVID-19 disease were identified. The median age was 69 years (range 38-91). Out of the 214 (63%) patients with the history of therapy for CLL, 97 (45%) were receiving CLL-directed treatment at diagnosis of COVID-19: 29% Bruton tyrosine kinase inhibitor (BTKi), 16% chemoimmunotherapy (CIT), 11% Bcl-2 inhibitor, and 4% phosphoinositide 3-kinase inhibitor. Regarding the severity of COVID-19, 60% pts required admission to the hospital, 21% pts were admitted to the intensive care unit (ICU), and 12% received invasive mechanical ventilation. The overall case fatality rate was 28%. Major comorbidities, age over 72, male gender, CLL treatment in history, CLL-directed treatment at COVID-19 diagnosis were associated with increased risk of death. Of note, concurrent therapy with BTKi compared to CIT was not associated with better outcome of COVID-19.

Real-world data on efficacy and safety of obinutuzumab plus chlorambucil, rituximab plus chlorambucil, and rituximab plus bendamustine in the frontline treatment of chronic lymphocytic leukemia: The GO-CLLEAR Study by the Czech CLL Study Group.

Until recently, a combination of anti-CD20 antibody plus less intensive chemotherapy was a standard of care in elderly population with previously untreated chronic lymphocytic leukemia (CLL). The aim of this observational study was to retrospectively assess efficacy and safety of obinutuzumab + chlorambucil (G-Clb), rituximab + chlorambucil (R-Clb), and bendamustine + rituximab (BR) given as the frontline therapy within routine practice. The final analyzed dataset included 398 consecutive CLL patients from 10 hematology centers cooperating within the Czech CLL Study Group: 63 treated with G-Clb, 78 with R-Clb, and 257 with BR. There were no significant differences in prognostic and predictive markers among the groups. On the contrary, median age at the start of therapy and cumulative illness rating scale (CIRS) score was significantly higher in R-Clb group. Obinutuzumab plus chlorambucil regimen was preferably offered to elderly patients (compared to BR) with less severe comorbidities and lower CIRS score (compared to R-Clb). A time period when a treatment was indicated had also a strong impact on the choice of the regimen. The overall response rate reached 76% (30% complete remissions, CRs) in G-Clb, 75% (22% CRs) in R-Clb, and 85% (47% CRs) in BR group. Median event-free survival was 49.0 months for G-Clb, 20.3 months for R-Clb, and 37.0 months for BR group. Neutropenia grade ≥ 3 developed in 43% of G-Clb, 31% of R-Clb and in 49% of BR patients, grade ≥ 3 infections were recorded in 17% of G-Clb, 6.4% of R-Clb, and 17% of BR patients. In conclusion, real-world therapeutic activity of G-Clb appears to be at least comparable to prospective clinical trial data. R-Clb yields relatively good results in very old and severely comorbid patients.

[Long-term treatment of venous thromboembolism in patients with cancer]. / Dlouhodobá lécba tromboembolické nemoci u pacientu se zhoubným nádorem.

BACKGROUND: The treatment with low-molecular-weight heparin (LMWH) is recommended for patients with cancer associated thrombosis (CAT) during the first 6 months; the initial therapeutic dose can be reduced to 60-75 % after one month. The therapy should be reevaluated after 6 month and subsequent therapy using LMWH or warfarin is recommended indefinitely, unless the cancer is resolved or any major contraindications arise. AIMS: To analyze the usage of various treatment modalities in CAT patients after the initial 6 month period according to the course of cancer. PATIENTS AND METHODS: 87 patients with CAT were followed prospectively during the treatment period. The proportion of patients, in whom LMWH was replaced by warfarin during the first 6 months and during the entire follow up, was analyzed in relation to the course of the cancer. The χ2 test and χ2 test with Yates correction were used for the statistical evaluation. RESULTS: The median follow-up was 445 days, mean duration of follow up was 743 days. 6 months after the diagnosis of thrombosis 9/30 (31.0 %) patients with complete remission (CR) of the cancer were treated with warfarin, while only 3/12 (25 %), 0/9 (0 %) and 1/13 (7.7 %) of the patients with partial remission (PR), stable disease (SD) and progression, respectively, were treated with warfarin. Patients with CR and PR were more frequently treated with warfarin than patients with SD or progression (P = 0.02). 13 patients died during the first 6 months, and 8 patients were followed less than 6 months. During the entire follow up, 25/30 (83.3 %) patients with CR switched to warfarin, while only 5/12 (41.7 %), 1/9 (11.1 %) and 1/13 (7.7 %) patients with PR, SD, and progression, respectively, were treated with warfarin. The proportion of patients with CR which switched to warfarin was higher, than the proportion of patients with PR (P = 0.007), with SD (P = 0.0003), and with progression (P < 0.0001). Median time from thrombosis onset to the switch from LMWH to warfarin was 219 days in patients in complete remission after 6 months and was not reached in patients in PR,SD, and progression. CONCLUSIONS: The course of malignant disease is important for the choice of appropriate therapy of CAT after the initial period of LMWH therapy. The patients achieving complete remission are more prone to switch from LMWH to warfarin. KEY WORDS: cancer - low-molecular-weight-heparin - venous thromboembolism - warfarin.