Combined Treatment with Ibrutinib and Anti-CD38 Monoclonal Antibody Daratumumab in Relapsed/Refractory Chronic Lymphocytic Leukemia with TP53 Aberrations: Results of the Filo Phase II Study IDA53

Aurran-Schleinitz, Thérèse; Tomowiak, Cécile; Roos‐Weil, Damien; Ferrant, Emmanuelle; Mahé, Béatrice; Molina, Lysiane; Ysebaert, Loïc; Fornecker, Luc Mathieu; Michallet, Anne‐Sophie; Lévy, Vincent; Guièze, Romain; Delmer, Alain

doi:10.1182/blood-2022-163096

Cited by 3 publications

(1 citation statement)

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“…The combination of daratumumab with ibrutinib in CLL patients—untreated, refractory, or relapsed with a poor prognosis (e.g., 17p deletion and/or TP53 mutation)—is being studied in three active phase Ib/II clinical trials (NCT03447808, NCT03734198, NCT04230304). The initial results of the NCT03734198 study showed no significant objective responses compared with ibrutinib alone [ 14 ]. A recent strategy of immunotherapy uses bispecific Abs (Bi-Abs), which have more advantages than monospecific Abs.…”

Section: Introductionmentioning

confidence: 99%

The Value of Neutrophil Gelatinase-Associated Lipocalin Receptor as a Novel Partner of CD38 in Chronic Lymphocytic Leukemia: From an Adverse Prognostic Factor to a Potential Pharmacological Target?

Bauvois,

Chapiro,

Quiney

et al. 2023

Biomedicines

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Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of neoplastic B lymphocytes that escape death, and correlates with the expression of negative prognostic markers such as the CD38 antigen. Although certain new drugs approved by the US Food and Drug Administration improve the clinical outcome of CLL patients, drug resistance and disease relapse still occur. Like CD38, neutrophil gelatinase-associated lipocalin receptor (NGAL-R) is frequently overexpressed in CLL cells. Here, we evaluated the concomitant surface expression of NGAL-R and CD38 in leukemic blood cells from 52 CLL patients (37 untreated, 8 in clinical remission, and 7 relapsed). We provide evidence of a positive correlation between NGAL-R and CD38 levels both in the interpatient cohorts (p < 0.0001) and in individual patients, indicating a constitutive association of NGAL-R and CD38 at the cell level. Patients with progressing CLL showed a time-dependent increase in NGAL-R/CD38 levels. In treated CLL patients who achieved clinical remission, NGAL-R/CD38 levels were decreased, and were significantly lower than in the untreated and relapsed groups (p < 0.02). As NGAL-R and CD38 participate in CLL cell survival, envisioning their simultaneous inhibition with bispecific NGAL-R/CD38 antibodies capable of inducing leukemic cell death might provide therapeutic benefit for CLL patients.

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Section: Introductionmentioning

confidence: 99%

The Value of Neutrophil Gelatinase-Associated Lipocalin Receptor as a Novel Partner of CD38 in Chronic Lymphocytic Leukemia: From an Adverse Prognostic Factor to a Potential Pharmacological Target?

Bauvois,

Chapiro,

Quiney

et al. 2023

Biomedicines

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CD38/NAD+ glycohydrolase and associated antigens in chronic lymphocytic leukaemia: From interconnected signalling pathways to therapeutic strategies

Bauvois,

Nguyen-Khac,

Merle-Béral

et al. 2024

Biochimie

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Targeting the tumor microenvironment for treating double-refractory chronic lymphocytic leukemia

Lewis,

vom Stein,

Hallek

2024

Blood

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The introduction of BTK inhibitors and BCL2 antagonists to the treatment of chronic lymphocytic leukemia has revolutionized therapy and improved patient outcomes. These agents have replaced chemoimmunotherapy as standard of care. Despite this progress, a new group of patients is currently emerging, which has become refractory or intolerant to both classes of agents, creating an unmet medical need. Here, we propose that the targeted modulation of the tumor microenvironment provides new therapeutic options for this group of "double refractory" patients. Furthermore, we outline a sequential strategy for tumor microenvironment-directed combination therapies in CLL that can be tested in clinical protocols.

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Combined Treatment with Ibrutinib and Anti-CD38 Monoclonal Antibody Daratumumab in Relapsed/Refractory Chronic Lymphocytic Leukemia with TP53 Aberrations: Results of the Filo Phase II Study IDA53

Cited by 3 publications

References 0 publications

The Value of Neutrophil Gelatinase-Associated Lipocalin Receptor as a Novel Partner of CD38 in Chronic Lymphocytic Leukemia: From an Adverse Prognostic Factor to a Potential Pharmacological Target?

The Value of Neutrophil Gelatinase-Associated Lipocalin Receptor as a Novel Partner of CD38 in Chronic Lymphocytic Leukemia: From an Adverse Prognostic Factor to a Potential Pharmacological Target?

CD38/NAD+ glycohydrolase and associated antigens in chronic lymphocytic leukaemia: From interconnected signalling pathways to therapeutic strategies

Targeting the tumor microenvironment for treating double-refractory chronic lymphocytic leukemia

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