Effectiveness of ibrutinib as first‐line therapy for chronic lymphocytic leukemia patients and indirect comparison with rituximab‐bendamustine: Results of study on 486 cases outside clinical trials

Morabito, Fortunato; Tripepi, Giovanni; Poeta, Giovanni Del; Mauro, Francesca Romana; Reda, Gianluigi; Sportoletti, Paolo; Laurenti, Luca; Coscia, Marta; Herishanu, Yair; Bossio, Sabrina; Varettoni, Marzia; Murru, Roberta; Chiarenza, Annalisa; Visentin, Andrea; Condoluci, Adalgisa; Moia, Riccardo; Pietrasanta, Daniela; Loseto, Giacomo; Consoli, Ugo; Scortechini, Ilaria; Rossi, Francesca Maria; Zucchetto, Antonella; Al-Janazreh, Hamdi; Vigna, Ernesto; Martino, Enrica Antonia; Cassin, Ramona; D’Arrigo, Graziella; Galimberti, Sara; Rago, Angela; Angeletti, Ilaria; Biagi, Annalisa; Giudice, Ilaria Del; Bomben, Riccardo; Neri, Antonino; Fronza, Gilberto; Monti, Paola; Olivieri, Jacopo; Cutrona, Giovanna; Rossi, Davide; Cuneo, Antonio; Raimondo, Francesco Di; Gaïdano, Gianluca; Polliack, Aaron; Trentin, Livio; Foà, Robin; Ferrarini, Manlio; Gattei, Valter; Gentile, Massimo

doi:10.1002/ajh.26201

Cited by 3 publications

(3 citation statements)

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“…In Cox models, data were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). All covariates as well as all variables significantly unbalanced between the two study arms were jointly introduced into the same multiple Cox regression model (6). A propensity score matching analysis (1:1) with and without resampling was also carried out with a 0.2 caliper width.…”

Section: Discussionmentioning

confidence: 99%

“…The IGHV mutational status is one of the most important prognostic and predicted markers in CLL, being able to identify patients who might benefit most from a fixed-duration therapy ( 6 , 10 , 30 , 34 ). When PFS and TTNT curves were stratified for the IGHV status, we found that IB improvement was significant only for the U-IGHV patients.…”

Section: Discussionmentioning

confidence: 99%

“…The current frontline therapy of CLL patients can be either a continuous BTK inhibitor or a fixed-duration G-based therapy (1). Choosing between the two approaches remains a challenge, since a continuous treatment might offer better disease control for some aggressive subsets of patients, balanced however by an increased rate of long-term adverse events (AEs) and costs for the health system (6)(7)(8)(9). On the other hand, a fixed G-based therapy is administered for a short period, allowing the achievement of deep remission, which is likely to be less prone to the development of resistant clones, but requires an outpatient clinic admission (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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Therapeutic Monoclonal Antibody Therapies in Chronic Autoimmune Demyelinating Neuropathies

Briani

Visentin

2022

Neurotherapeutics

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SummaryAutoimmune diseases of the peripheral nervous system have so far been treated mainly with exogenous high-dose intravenous immunoglobulins (IVIg), that act through several mechanisms, including neutralization of pathogenic autoantibodies, modulation of lymphocyte activity, interference with antigen presentation, and interaction with Fc receptors, cytokines, and the complement system. Other therapeutic strategies have recently been developed, in part to address the increasing shortage of IVIg, prime among which is the use of B cell depleting monoclonal antibodies, or small molecule inhibitors targeting the B-cell specific kinases. Rituximab, a chimeric monoclonal antibody against CD20 + B lymphocytes, is currently the most used, especially in anti-MAG antibody neuropathy and autoimmune neuropathies with antibodies to nodal/paranodal antigens that are unresponsive to IVIg. After several reports of its efficacy in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), rituximab is currently under investigation in three Phase 2 trials in CIDP. In addition, the possible role of complement activation in the pathogenesis of chronic autoimmune neuropathies has brought into consideration drugs that can block the complement cascade, such as eculizumab, a monoclonal antibody already assessed in acute polyradiculoneuropathies, and approved for myasthenia gravis. Preliminary data on eculizumab in multifocal motor neuropathy have been published, but randomized controlled studies are pending. Moreover, the neonatal Fc receptor, that recycles IgGs by preventing their lysosome degradation, is an important and attractive pharmacological target. Antibodies against FcRn, which reduce circulating IgG (both pathogenic and non-pathogenic) have been developed. The FcRn blocker efgartigimod, a humanized IgG1-derived Fc fragment, which competitively inhibits the FcRn, has recently been approved for the treatment of myasthenia gravis and is currently under investigation in CIDP. In addition, the anti-human FcRn monoclonal antibody rozanolixizumab is currently being assessed in phase 2 trials in CIDP. However, none of the abovementioned monoclonal antibodies is currently approved for treatment of any immune-mediated neuropathies. While more specific and individualized therapies are being developed, the possibility of combined treatments targeting different pathogenic mechanisms deserves consideration as well.

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Bruton tyrosine kinase inhibitors: can they be optimized for the treatment of neuroinflammatory disorders?

Visentin,

Puthenparampil,

Briani

2023

Expert Opinion on Investigational Drugs

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Effectiveness of ibrutinib as first‐line therapy for chronic lymphocytic leukemia patients and indirect comparison with rituximab‐bendamustine: Results of study on 486 cases outside clinical trials

Cited by 3 publications

References 7 publications

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

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

Therapeutic Monoclonal Antibody Therapies in Chronic Autoimmune Demyelinating Neuropathies

Bruton tyrosine kinase inhibitors: can they be optimized for the treatment of neuroinflammatory disorders?

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