scholarly journals Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia

2021 ◽  
pp. 1-16
Author(s):  
Matthew S. Davids ◽  
Claire Telford ◽  
Sarang Abhyankar ◽  
Catherine Waweru ◽  
Ingo Ringshausen
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Targeted Therapies ◽  
Lymphocytic Leukemia ◽  
Safety And Efficacy ◽  
Treatment Naïve ◽  
Indirect Comparisons

scholarly journals Safety and efficacy of BNT162b mRNA Covid19 Vaccine in patients with chronic lymphocytic leukemia

Haematologica ◽  
2021 ◽  
Author(s):  
Ohad Benjamini ◽  
Lior Rokach ◽  
Gilad Itchaki ◽  
Andrei Braester ◽  
Lev Shvidel ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Humoral Response ◽  
Lymphocytic Leukemia ◽  
Safety And Efficacy ◽  
Patient Will ◽  
Treatment Naïve ◽  
High Concordance ◽  
Anti Cd20

Patients with chronic lymphocytic leukemia (CLL) have a suboptimal humoral response to vaccination. Recently, a BNT162b2 mRNA COVID-19 vaccine was introduced with a high efficacy of 95% in immunocompetent individuals. We investigated the safety and efficacy of BNT162b2 mRNA Covid-19 vaccine in patients with CLL from nine medical centers in Israel, In total 400 patients were included, of which 373 were found to be eligible for the analysis of antibody response. The vaccine appeared to be safe and only grade 1-2 adverse events were seen in 50% of the patients. Following the second dose, antibody response was detected in 43% of the cohort. In treatment- naïve patients 61% responded to the vaccine, while only 18%, 37% and 5% of patients with CLL ongoing, previously treated with BTKi, or recent anti CD20 antibody developed responses respectively. 62% and 14% of patients treated with BCL2 monotherapy or combined with anti CD20 developed immune response respectively. Neutralizing antibodies demonstrated high concordance with positive serologic response to spike (S) protein. Based on our results a simple scoring model including recent treatment with anti-CD20, age younger than 70 years, treatment naïve status, and normal IGG, IGA, IGM and hemoglobin levels. The sum of all the above parameters can serve as a possible estimate to predict whether a given CLL patient will develop sufficient antibodies. In conclusion, the vaccine was found to be safe in patients with CLL, but its efficacy is limited particularly in treated patients.

scholarly journals “Double-Hit” Chronic Lymphocytic Leukemia, Involving the TP53 and MYC Genes

2022 ◽  
Vol 11 ◽  
Author(s):  
Florence Nguyen-Khac
Keyword(s):  
Prognostic Factor ◽  
Chronic Lymphocytic Leukemia ◽  
Targeted Therapies ◽  
Poor Prognosis ◽  
Kinase Inhibitors ◽  
Lymphocytic Leukemia ◽  
Prognostic Impact ◽  
Bruton Tyrosine Kinase ◽  
Treatment Naïve ◽  
Double Hit

Although the 17p deletion [del(17p)] is rare in cases of treatment-naive chronic lymphocytic leukemia (CLL), its frequency is higher in refractory/relapsed CLL – particularly in patients undergoing chemo(immuno)therapy. TP53 disruption (deletion and/or mutation) is the strongest prognostic factor for refractoriness to chemotherapy; the use of Bruton tyrosine kinase inhibitors and BCL2 inhibitors is then indicated. Rare cases of CLL can also harbor translocation or gain of the MYC oncogene. “Double-hit CLL” (with del(17p) and MYC gain) is associated with a very poor prognosis. The prognostic impact of TP53 disruption with MYC aberrations in patients receiving targeted therapies must now be evaluated.

scholarly journals Challenges with Approved Targeted Therapies against Recurrent Mutations in CLL: A Place for New Actionable Targets

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3150
Author(s):  
Irene López-Oreja ◽  
Heribert Playa-Albinyana ◽  
Fabián Arenas ◽  
Mónica López-Guerra ◽  
Dolors Colomer
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Targeted Therapies ◽  
Biological Pathways ◽  
Lymphocytic Leukemia ◽  
Pi3k Inhibitors ◽  
Recurrent Mutations ◽  
Treatment Responses ◽  
Few Data ◽  
High Degree ◽  
Btk Inhibitors

Chronic lymphocytic leukemia (CLL) is characterized by a high degree of genetic variability and interpatient heterogeneity. In the last decade, novel alterations have been described. Some of them impact on the prognosis and evolution of patients. The approval of BTK inhibitors, PI3K inhibitors and Bcl-2 inhibitors has drastically changed the treatment of patients with CLL. The effect of these new targeted therapies has been widely analyzed in TP53-mutated cases, but few data exist about the response of patients carrying other recurrent mutations. In this review, we describe the biological pathways recurrently altered in CLL that might have an impact on the response to these new therapies together with the possibility to use new actionable targets to optimize treatment responses.

scholarly journals Single-agent ibrutinib versus chemoimmunotherapy regimens for treatment-naïve patients with chronic lymphocytic leukemia: A cross-trial comparison of phase 3 studies

2018 ◽  
Vol 93 (11) ◽  
pp. 1402-1410 ◽  
Author(s):  
Tadeusz Robak ◽  
Jan A. Burger ◽  
Alessandra Tedeschi ◽  
Paul M. Barr ◽  
Carolyn Owen ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Single Agent ◽  
Lymphocytic Leukemia ◽  
Phase 3 ◽  
Treatment Naïve

BiallelicATMalterations detected at diagnosis identify a subset of treatment-naïve chronic lymphocytic leukemia patients with reduced overall survival similar to patients with p53 deletion

2016 ◽  
Vol 58 (4) ◽  
pp. 859-865 ◽  
Author(s):  
Carol Lozano-Santos ◽  
José A. García-Vela ◽  
Nuria Pérez-Sanz ◽  
Sara Nova-Gurumeta ◽  
Belen Fernandez-Cuevas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Treatment Naïve

scholarly journals Activation of hedgehog signaling associates with early disease progression in chronic lymphocytic leukemia

Blood ◽  
2019 ◽  
Vol 133 (25) ◽  
pp. 2651-2663 ◽  
Author(s):  
Emanuela M. Ghia ◽  
Laura Z. Rassenti ◽  
Donna S. Neuberg ◽  
Alejandro Blanco ◽  
Fouad Yousif ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Disease Progression ◽  
Hedgehog Signaling ◽  
Lymphocytic Leukemia ◽  
Early Disease ◽  
Mutation Status ◽  
Enhanced Sensitivity ◽  
Genes Encoding ◽  
Treatment Naïve ◽  
Hh Signaling

Abstract Targeted sequencing of 103 leukemia-associated genes in leukemia cells from 841 treatment-naive patients with chronic lymphocytic leukemia (CLL) identified 89 (11%) patients as having CLL cells with mutations in genes encoding proteins that putatively are involved in hedgehog (Hh) signaling. Consistent with this finding, there was a significant association between the presence of these mutations and the expression of GLI1 (χ2 test, P < .0001), reflecting activation of the Hh pathway. However, we discovered that 38% of cases without identified mutations also were GLI1+. Patients with GLI1+ CLL cells had a shorter median treatment-free survival than patients with CLL cells lacking expression of GLI1 independent of IGHV mutation status. We found that GANT61, a small molecule that can inhibit GLI1, was highly cytotoxic for GLI1+ CLL cells relative to that of CLL cells without GLI1. Collectively, this study shows that a large proportion of patients have CLL cells with activated Hh signaling, which is associated with early disease progression and enhanced sensitivity to inhibition of GLI1.

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