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Despite lower virulence, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) still poses a relevant threat for immunocompromised patients. A retrospective multicentric study was conducted to evaluate the efficacy of pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) with a 6-month follow-up for preventing severe COVID-19 in adult patients with hematology malignancy. Among the 606 patients in the cohort, 96 (16%) contracted COVID-19 with a median of 98.5 days after Evusheld administration. A total of 75% of patients had asymptomatic or mild severity of COVID-19, while just 25% of patients with SARS-CoV-2 positivity had to be hospitalized. Two patients (2%) died directly, and one patient (1%) in association with COVID-19. Eight patients (1.3%) of every cohort experienced adverse events related to Evusheld, mostly grade 1 and of reversible character. It was found that complete vaccination status or positive seroconversion was not associated with lower risk of COVID-19 infection. Previous treatment with an anti-CD20 monoclonal antibody was associated with higher rates of COVID-19, while previous treatment with anti-CD38 monoclonal antibody was not, as was the case for recipients of hematopoietic stem cell transplantation or CAR-T cell therapy. Presence of other comorbidities was not associated with more severe COVID-19. The results support the growing evidence for Evusheld's efficacy against severe COVID-19 in patients with hematology malignancies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Therapeutic options used to be very limited for treatment‐naïve elderly/comorbid patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) before the introduction of chemo‐immunotherapy. Because dose‐reduced fludarabine‐based regimens yielded promising results, the Czech CLL Study Group initiated a prospective observational study to assess safety and efficacy of low‐dose fludarabine and cyclophosphamide combined with rituximab (FCR) in elderly/comorbid patients. Between March 2009 and July 2012, we enrolled 107 patients considered ineligible for full‐dose FCR (median age, 70 years; median Cumulative Illness Rating Scale score, 5; median creatinine clearance, 69 ml/min). Notably, 77% patients had unfavourable biological prognosis [unmutated immunoglobulin heavy‐chain variable‐region gene (IGHV), 74%; deletion 17p, 9%). Fludarabine was reduced to 12 mg/m2 intravenously (iv) or 20 mg/m2 orally on days 1–3 and cyclophosphamide to 150 mg/m2 iv/orally on days 1–3. Grade 3–4 neutropenia occurred in 56% of the patients, but there were serious infections in only 15%. The median progression‐free survival was 29 months, but was markedly longer in patients with mutated IGHV (median 53 months), especially in absence of del 11q or 17p (median 74 months). Low‐dose FCR is a well‐tolerated and effective first‐line regimen for selected elderly/comorbid patients with CLL/SLL with favourable biology. The study was registered at clinicaltrials.gov (NCT02156726). [ABSTRACT FROM AUTHOR]

High doses of corticosteroids in combination with rituximab remain an alternative in the treatment in relapsed or refractory chronic lymphocytic leukaemia (CLL) in the current era of targeted therapies. This study retrospectively evaluates the efficacy of an RCD (rituximab, cyclophosphamide and dexamethasone) regimen in the treatment of 51 patients with relapsed CLL (median age, 72 years). Unfavourable prognostic features, such as Rai stage III/IV, unmutated IGHV, del11q, TP53 mutation/deletion, complex karyotype and bulky lymphadenopathy, were frequent. The overall response or complete remission was of 57% and 7%, respectively, and the median progression‐free survival (PFS) was of 12.3 months, median time to next treatment 23.1 months and median overall survival 39.2 months. Significant independent predictors of shorter PFS were TP53 deletion/mutation, advanced Rai stage and ≥2 previous lines of treatment. The incidence of neutropenia grade ≥ 3 was of 13%. Serious (CTCAE grade 3‐5) infections were found in 20% of patients. Steroid‐induced diabetes or diabetes decompensation occurred in 20% patients. Treatment‐related adverse events resulted in RCD dose reduction in 35% of patients. In comparison with a historical R‐Dex patient group, the treatment response and/or toxicity in our group was largely similar. However, the substantial differences in the baseline clinical characteristics of the groups may affect this comparison. In conclusion, the RCD regimen is an active, time‐limited therapeutic strategy for elderly patients with relapsed CLL. Further, the results of our analysis indicate that the addition of cyclophosphamide to the R‐Dex regimen maintains a similar efficacy, even after 50% reduction in the dexamethasone dose. [ABSTRACT FROM AUTHOR]

Summary: Most patients with chronic lymphocytic leukaemia (CLL) are nowadays diagnosed without any symptoms and do not require therapy. A prognostic score identifying patients within this large group who are at high risk of disease progression would be highly beneficial. The recently published International Prognostic Score for Early asymptomatic patients (IPS‐E) uses combination of absolute lymphocyte count (ALC) >15 × 109/l, palpable lymphadenopathy, and unmutated immunoglobulin heavy‐chain variable‐region (IGHV) gene to predict the time to first‐line therapy (TTFT). Patients at low, intermediate, and high risk had estimated 5‐year TTFT of 8%, 28%, and 61%. We performed an external validation of the IPS‐E score using an unselected, consecutive group of 130 Binet A patients. The 5‐year TTFT was 11%, 36%, and 78% (C‐statistic 0·74). Furthermore, we propose an alternative system (AIPS‐E) using cytogenetic aberrations instead of palpable lymphadenopathy. This system yielded 5‐year TTFT of 14%, 40%, and 72%. These results were externally validated in 388 Binet A patients from five Czech centres; the 5‐year TTFT was 16%, 37%, and 80% (C‐statistic 0·74). In conclusion, we have successfully validated the IPS‐E score for patients with early stage CLL. In addition, we propose a modified scoring system, the AIPS‐E, combining IGHV, fluorescence in situ hybridisation, and ALC. [ABSTRACT FROM AUTHOR]

Optimal frontline treatment in younger high tumor-burden risk follicular lymphoma patients remains a challenge given the reduced efficacy of standard immunochemotherapy (R-CHOP) in widespread disease and unclear role of intensive induction. The retrospective non-randomized pair-matched (1:3) analysis compared 48 intermediate/high Follicular Lymphoma International Prognostic Index (FLIPI) patients receiving intensive rituximab sequential chemotherapy (R-SQ) with 144 random controls (R-CHOP) matched for age, FLIPI score, and maintenance delivery. Complete response rates were 91.7% and 74.1%, respectively (p = .038). After a median follow-up of 8.8 (R-SQ) and 6.5 years (R-CHOP), 5-year time to treatment failure, progression-free survival, and overall survival were 80.9%, 83.2%, and 100% and 57.5%, 60.3%, and 92.1% (p = .0044;p = .0047;p = .22), respectively. Intensive treatment was accompanied by higher acute hematologic toxicity and infections, comparable non-hematologic toxicity, and incidence of secondary malignancies. Intensive induction demonstrates superior long-term disease control compared to R-CHOP, with higher acute hematologic toxicity, but without acute treatment-related mortality. Further studies are needed to define ultra-high-risk FL patients benefiting most from treatment intensity. [ABSTRACT FROM PUBLISHER]