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

Visentin, Andrea; Mauro, Francesca Romana; Catania, Gioachino; Fresa, Alberto; Vitale, Candida; Sanna, Alessandro; Mattiello, Veronica; Cibien, Francesca; Sportoletti, Paolo; Gentile, Massimo; Rigolin, Gian Matteo; Quaglia, Francesca Maria; Murru, Roberta; Gozzetti, Alessandro; Molica, Stefano; Marchetti, Monia; Pravato, Stefano; Angotzi, Francesco; Cellini, Alessandro; Scarfò, Lydia; Reda, Gianluigi; Coscia, Marta; Laurenti, Luca; Ghia, Paolo; Foà, Robin; Cuneo, Antonio; Trentin, Livio

doi:10.3389/fonc.2022.1033413

Cited by 9 publications

(7 citation statements)

References 42 publications

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“…For unknown reasons, obinutuzumab-based treatment seems to be highly toxic in patients with anti-MAG neuropathy as compared with other real-world evidence studies in patients with CLL. 25 , 26 …”

Section: Resultsmentioning

confidence: 99%

Mutational Profile in 75 Patients With Anti–Myelin-Associated Glycoprotein Neuropathy

Castellani

Visentin

Schirinzi

et al. 2023

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesNeuropathy with antibodies to myelin-associated glycoprotein (MAG) is the most common paraproteinemic IgM neuropathy. Recently, the mutational profile of theMYD88andCXCR4genes has been included in the diagnostic workup of IgM monoclonal gammopathies. The objective of our study was to assess the prevalence ofMYD88L265PandCXCR4S338Xgene variants in patients with anti-MAG antibody neuropathy. Secondary aims were to evaluate possible correlations between the mutational profile and neuropathy severity, antibody titers, and treatment response.MethodsSeventy-five patients (47 men, mean age at molecular analysis 70.8 ± 10.2 years; mean disease duration 5.1 ± 4.9 years) with anti-MAG antibody neuropathy were recruited. Among them, 38 (50.7%) had IgM monoclonal gammopathy of undetermined significance, 29 (38.7%) Waldenstrom macroglobulinemia (WM), and 8 (10.6%) chronic lymphocytic leukemia/marginal zone lymphoma/hairy cell leukemia variant. Molecular analysis was performed on DNA from the bone marrow mononuclear cells in 55 of 75 patients and from peripheral mononuclear cells in 18 of 75 patients. Forty-five patients were treated with rituximab, 6 with ibrutinib, 2 with obinutuzumab-chlorambucil, and 3 with venetoclax-based therapy. All the patients were assessed with the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Scale, INCAT Sensory Sum Score, and MRC Sum Score at baseline and follow-up. We considered as responders, patients who improved by at least 1 point in 2 clinical scales.ResultsFifty patients (66.7%) carried theMYD88L265Pvariant, with a higher frequency in WM and naive patients (77.2% vs 33.3%,p= 0.0012). No patients harbored theCXCR4S338Xvariant. There were no significant differences in hematologic data (IgM levels, M protein, and anti-MAG antibody titers), neuropathy severity, or response to rituximab inMYD88-altered andMYD88wild-type patients. Nine of 11 (81.8%) patients treated with novel targeted drug, according to theMYD88status, responded to treatments.DiscussionMYD88L265Pvariant has a high prevalence (66.7%) in anti-MAG antibody neuropathy representing a potential effective mutational target for Bruton tyrosine kinase inhibitors. MYD88L265Pvariant, however, does not seem to be a prognostic factor of neuropathy severity or response to rituximab. In patients not responding or becoming refractory to rituximab, a tailored therapy with new effective target therapies should be considered.

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Section: Resultsmentioning

confidence: 99%

Mutational Profile in 75 Patients With Anti–Myelin-Associated Glycoprotein Neuropathy

Castellani

Visentin

Schirinzi

et al. 2023

Neurol Neuroimmunol Neuroinflamm

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“…We found a higher reporting of atrial fibrillation with ibrutinib therapy. Accordingly, a retrospective study found a lower development of atrial fibrillation in patients affected by CLL treated with obinutuzumab plus chlorambucil than ibrutinib in spite of a not statistically significant difference (2% vs. 9%, p = 0.0813) ( Visentin et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Which is the top player for the cardiovascular safety? ibrutinib vs. obinutuzumab in CLL

Mascolo,

Di Napoli,

Balzano

et al. 2023

Front. Pharmacol.

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Introduction: Ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, is authorized for the treatment of chronic lymphocytic leukemia (CLL). This study aims to explore the cardiac safety profile of ibrutinib in comparison with obinutuzumab.Methods: A retrospective pharmacovigilance study was conducted on data retrieved from the European pharmacovigilance database (Eudravigilance) from 1 January 2014 to 30 September 2022. To compare the reporting frequency of cardiovascular events among ibrutinib, obinutuzumab, and the combination of both.Results: A total of 2 291 CV cases were retrieved, of which 1965 were related to ibrutinib, 312 to obinutuzumab, and 14 to the combination. Most cases referred to patients aged ≥65 years (N = 1,454; 63.47%) and male (N = 1,497; 65.34%). Most cases were serious (N = 2,131; 93.02%). The most reported events were: atrial fibrillation (N = 913; 31.31%) and haemorrhage (N = 201; 6.89%). A higher reporting frequency of CV events was found when ibrutinib was compared to obinutuzumab (ROR, 3.22; 95% CI, 2.89-3.60) or combination (ROR, 1.77; 95% CI, 1.11-2.83). A lower reporting was observed when obinutuzumab was compared to combination (ROR, 0.55; 95% CI, 0.34-0.88).Discussion: A higher reporting frequency of CV events in patients exposed to ibrutinib in comparison with obinutuzumab was found. Further studies are needed to better explore the safety of ibrutinib.

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“…An indirect comparison of CIT with Chlor + O and ibrutinib was performed with the Italian CLL campus network [82]. Patients with TP53 disruptions were excluded.…”

Section: Real-world Evidencementioning

confidence: 99%

First-Line Treatment of Older Patients with CLL: A New Approach in the Chemo-Free Era

Urso,

Cavazzini,

Ballardini

et al. 2023

Cancers

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Bruton tyrosine kinase inhibitors (BTKi) and the BCL2 inhibitor venetoclax, with or without the anti-CD20 monoclonal antibody Obinutuzumab, represent the preferred options for the first-line therapy of CLL because they are more effective and may improve quality of life. However, patient inclusion criteria are heterogeneous across trials designed for older patients, and the identification of CLL-specific parameters identifying unfit patients at risk of developing drug-specific adverse events is required to guide treatment choice. Due to inclusion/exclusion criteria in trials, higher discontinuation rates with BTKi were reported in real-world studies, and registry analyses provided useful information on factors predicting earlier discontinuation in a real-world setting. Though targeted agents were shown to be cost-effective treatments in high-income countries, the out-of-pocket expenses may limit accessibility to these drugs, and the overall expenditure for new drugs in CLL is projected to increase substantially, posing an issue for sustainability. This being said, the choice of a finite-duration treatment based on venetoclax-containing regimens or treatment until progression with BTKi is today possible in high-income countries, and the therapy choice drivers are represented by coexisting medical conditions rather than age, patient expectations, logistics, and sustainability.

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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

Cited by 9 publications

References 42 publications

Mutational Profile in 75 Patients With Anti–Myelin-Associated Glycoprotein Neuropathy

Mutational Profile in 75 Patients With Anti–Myelin-Associated Glycoprotein Neuropathy

Which is the top player for the cardiovascular safety? ibrutinib vs. obinutuzumab in CLL

First-Line Treatment of Older Patients with CLL: A New Approach in the Chemo-Free Era

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