Continuous treatment with Ibrutinib in 100 untreated patients with <i>TP</i>53 disrupted chronic lymphocytic leukemia: A real‐life campus CLL study

Visentin, Andrea; Mauro, Francesca Romana; Cibien, Francesca; Vitale, Candida; Reda, Gianluigi; Fresa, Alberto; Ciolli, Stefania; Pietrasanta, Daniela; Marchetti, Monia; Murru, Roberta; Gentile, Massimo; Rigolin, Gian Matteo; Quaglia, Francesca Maria; Scarfò, Lydia; Sportoletti, Paolo; Pravato, Stefano; Coscia, Marta; Laurenti, Luca; Molica, Stefano; Foà, Robin; Cuneo, Antonio; Trentin, Livio

doi:10.1002/ajh.26437

Cited by 19 publications

(20 citation statements)

References 15 publications

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“…Testing and documentation of TP53 alterations regardless of clonal burden should still be performed for patients receiving firstline BTKi for CLL. We did not find a significant association between multi-hit TP53 and PFS which differs from the findings of other studies 20,29 which did report worse outcomes for patients with multi-hit TP53. This difference may be explained by the fact those studies analyzed patients uniformly treated with ibrutinib monotherapy and Brieghel and colleagues 20 analyzed a significant number of patients treated in the relapsed setting.…”

Section: (B) (A)contrasting

confidence: 99%

TP53‐altered chronic lymphocytic leukemia treated with firstline Bruton's tyrosine kinase inhibitor‐based therapy: A retrospective analysis

et al. 2022

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Long-term follow up of prospective studies has shown that continuous Bruton's tyrosine kinase inhibitor (BTKi) therapy leads to durable remissions in previously untreated patients with TP53-altered chronic lymphocytic leukemia (CLL); however, it is unknown how variant allele frequency (VAF) of TP53 mutation (TP53-m) or percentage of cells with deletion of chromosome 17p [del(17p)] influences efficacy of firstline BTKi. We performed a retrospective analysis of 130 patients with CLL with baseline del(17p) and/or TP53-m treated with BTKi with or without the BCL2 inhibitor venetoclax (VEN) and with or without CD20 antibody in the firstline setting. A total of 104/130 (80%) patients had del(17p). TP53-m was noted in 89/110 (81%) patients tested; there were 101 unique TP53-m with an available VAF. The 4-year progression-free survival (PFS) and overall survival (OS) rates were 72.9% and 83.6%.No baseline characteristics including IGHV mutation status and number of TP53 alterations were associated with significant differences in PFS or OS, though a trend toward shorter PFS with increasing karyotypic complexity (hazard ratio 1.08, p = .066) was observed. Del(17p) was identified in <25% of cells in 26/104 (25%) of patients, and 28/101 (28%) of TP53-m were low-burden with a VAF of <10%; outcomes of these patients were similar to those with high-burden lesions. This study suggests that low-burden TP53 alterations should not be ignored when assessing genomic risk in CLL in the era of targeted therapy.

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Section: (B) (A)contrasting

confidence: 99%

TP53‐altered chronic lymphocytic leukemia treated with firstline Bruton's tyrosine kinase inhibitor‐based therapy: A retrospective analysis

et al. 2022

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“…One-hundred patients were previously reported (24). Data cut-off was set to May 2022; therefore, all patients have a minimum potential follow-up period of at least 16 months.…”

Section: Resultsmentioning

confidence: 99%

Outcomes in patients with chronic lymphocytic leukemia and TP53 aberration who received first line ibrutinib: a nationwide registry study from the Italian Medicines Agency

Rigolin

Olimpieri²,

Summa³

et al. 2023

Preprint

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In this analysis we describe the effectiveness of first-line ibrutinib in 747 patients with chronic lymphocytic leukemia (CLL) and TP53 aberrations in a nationwide study with a 100% capture of patients who received the study drug. Median age was 71 years (range 32-95). An estimated treatment persistence rate of 63.4% (95% CI 60.0%-67.0%) and survival rate of 82.6% (95% CI 79.9%-85.4%) were recorded at 24 months. Disease progression or death were the reasons for discontinuation in 182/397 patients (45.8%). A higher risk of treatment discontinuation was found to be associated with age, ECOG-PS and pre-existing heart disease, whereas ECOG≥1, age≥70 years and male sex were associated with an increased risk of death. Median post-progression overall survival (OS) was 12.2 months (95% CI 9.2-22.0). Post-discontinuation median OS in patients who discontinued ibrutinib for other reasons was not reached (95% CI 42.3 months – NA). Ibrutinib was an effective first-line treatment for CLL and TP53 aberrations in patients treated at large academic centers and community practice hospitals. Clinical characteristics at baseline may influence the effectiveness of ibrutinib, whereas the experience of prescribing centers and multi-hit or single-hit TP53 aberrations had no impact on outcome in this high-risk population.

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“…We collected data of 284 patients from 16 Italian hematological centers within the Italian CLL campus network; 104 patients received G-CHL as frontline treatment and 180 patients were treated with IB. As shown in the consort plot, we excluded 101 patients due to the presence TP53 abnormalities: 1 subject in the G-CHL arm, and 100 patients in the IB arm [the latter has been previously published ( 28 )]. For the final analysis, we included patients without TP53 abnormalities: 103 patients treated with G-CHL and 80 patients treated with IB ( Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

Obinutuzumab plus chlorambucil versus ibrutinib in previously untreated chronic lymphocytic leukemia patients without TP53 disruptions: A real-life CLL campus study

et al. 2022

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One of the main issues in the treatment of patients with chronic lymphocytic leukemia (CLL) deals with the choice between continuous or fixed-duration therapy. Continuous ibrutinib (IB), the first-in-class BTK inhibitor, and obinutuzumab-chlorambucil (G-CHL) are commonly used therapies for elderly and/or comorbid patients. No head-to-head comparison has been carried out. Within the Italian campus CLL network, we performed a retrospective study on CLL patients without TP53 disruption treated with IB or G-CHL as first-line therapy. Patients in the G-CHL arm had a higher CIRS score and the worst renal function. The overall response rates between the G-CHL and IB arms were similar, but more complete remissions (CRs) were achieved with G-CHL (p = 0.0029). After a median follow-up of 30 months, the progression-free survival (PFS, p = 0.0061) and time to next treatment (TTNT, p = 0.0043), but not overall survival (OS, p = 0.6642), were better with IB than with G-CHL. Similar results were found after propensity score matching and multivariate analysis. While PFS and TTNT were longer with IB than with G-CHL in IGHV unmutated patients (p = 0.0190 and 0.0137), they were superimposable for IGHV mutated patients (p = 0.1900 and 0.1380). In the G-CHL arm, the depth of response (79% vs. 68% vs. 38% for CR, PR and SD/PD; p < 0.0001) and measurable residual disease (MRD) influenced PFS (78% vs. 53% for undetectable MRD vs. detectable MRD, p = 0.0203). Hematological toxicities were common in the G-CHL arm, while IB was associated with higher costs. Although continuous IB provides better disease control in CLL, IGHV mutated patients and those achieving an undetectable MRD show a marked clinical and economic benefit from a fixed-duration obinutuzumab-based treatment.

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Continuous treatment with Ibrutinib in 100 untreated patients with TP53 disrupted chronic lymphocytic leukemia: A real‐life campus CLL study

Abstract: The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: results of a 17-year, single-center trial (LaSHS).

Cited by 19 publications

References 15 publications

TP53‐altered chronic lymphocytic leukemia treated with firstline Bruton's tyrosine kinase inhibitor‐based therapy: A retrospective analysis

TP53‐altered chronic lymphocytic leukemia treated with firstline Bruton's tyrosine kinase inhibitor‐based therapy: A retrospective analysis

Outcomes in patients with chronic lymphocytic leukemia and TP53 aberration who received first line ibrutinib: a nationwide registry study from the Italian Medicines Agency

Obinutuzumab plus chlorambucil versus ibrutinib in previously untreated chronic lymphocytic leukemia patients without TP53 disruptions: A real-life CLL campus study

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