Front-line chemo-immunotherapy is not inferior to ibrutinib in CLL

Gelder, Michel van; Tournilhac, Olivier; Raa, Doreen te; Visser, Hein P.J.

doi:10.1016/j.annonc.2021.08.1990

Cited by 2 publications

(2 citation statements)

References 6 publications

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“…Also, acalabrutinib and Ven-O were superior in terms of PFS, as compared to Clb-O in this patient subgroup [43,46]. However, currently there is a discussion going on in the Netherlands concerning the clinical importance of PFS in a chronic disease such as CLL [48]. Differential findings in PFS are frequently based on the performance of routine CT scans within the framework of clinical trials.…”

Section: Unmutated Ighv Genes Without Tp53 Aberrationsmentioning

confidence: 99%

Diagnosis, treatment and supportive management of chronic lymphocytic leukemia: recommendations of the Dutch HOVON CLL working group

Raa

Straten

Gelder

et al. 2022

Leukemia & Lymphoma

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Management of patients with chronic lymphocytic leukemia (CLL) is changing due to considerable advances in the therapeutic armamentarium, and new therapies will possibly continue to emerge in the near future. Therefore, the CLL working group of the Dutch-Belgium Haemato-Oncology Cooperative Group for Adults in the Netherlands (HOVON) necessitated revising the Dutch CLL guidelines. The current guideline is based on the expert opinion of the HOVON CLL working group members and focusses on well-designed clinical trials taking into account efficacy with special emphasis on toxicity, treatment duration and treatment intensity. This article provides recommendations on diagnosis, treatment strategies in front-line and relapsed setting and provides supportive care measurements during novel-based therapies as well as for infectious CLL-related complications. The recommendations presented here are intended to provide guidance for the management of CLL patients in the Netherlands, and take into account the availability of treatment strategies at the time of this publication.

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Section: Unmutated Ighv Genes Without Tp53 Aberrationsmentioning

confidence: 99%

Diagnosis, treatment and supportive management of chronic lymphocytic leukemia: recommendations of the Dutch HOVON CLL working group

Raa

Straten

Gelder

et al. 2022

Leukemia & Lymphoma

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“…Chemo‐immunotherapy has shown great success in boosting systemic anti‐tumor effects in the clinic. [ 1 ] However, when cancer cells are treated with antimetabolic chemotherapeutic agents, such as mitoxantrone (MTO), the metabolic pattern of tumor cells is switched. [ 2 ] In order to ensure a supply of nutrients, tumor cells tend to take nutrients from the extracellular microenvironment by macropinocytosis, thus maintaining a high energetic metabolism level to escape the effect of chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Clinical Chemotherapeutic Agent Coordinated Copper‐Based Nanoadjuvants for Efficiently Sensitizing Cancer Chemo‐Immunotherapy by Cuproptosis‐Mediated Mitochondrial Metabolic Reprogramming

Tian,

Duan,

et al. 2023

Adv Funct Materials

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Chemo‐immunotherapy has shown great success in boosting systemic anti‐tumor effects in the clinic. However, cancer cells can escape the maximum impact of chemotherapy through intracellular symbiotic bacteria and abnormally activated macropinocytosis, while cancer immune evasion is largely facilitated by the programmed cell death 1 ligand 1 (PD‐L1) protein and tumor‐secreted exosomes. To efficiently sensitize chemo‐immunotherapy, the clinical mitoxantrone (MTO) is therefore rationally coordinated with Cu2+ to develop nanoscale metal‐organic frameworks (MTO‐Cu), then loaded with the macropinocytosis and exosome secretion inhibitor amiloride (AMI) and modified with targeted chondroitin sulfate (CS) to form CS/MTO‐Cu@AMI nanoadjuvant. Notably, the coordinated Cu2+ effectively triggers cuproptosis‐induced mitochondrial dysfunction, which activates AMPK pathway‐mediated PD‐L1 protein degradation, deprives energy supply for macropinocytosis and exosome release, and amplifies oxidative stress for deactivating intracellular bacteria, thus efficiently sensitizing chemo‐immunotherapy. Meanwhile, AMI suppresses macropinocytosis and exosome secretion to act synergistically with Cu2+‐caused chemo‐immunotherapy potentiation. Moreover, damaged dsDNA during CS/MTO‐Cu@AMI treatment activates the cGAS‐STING pathway, further evoking the anti‐tumor immunity. Additionally, the attached CS endows CS/MTO‐Cu@AMI with specific tumor targeting and hyaluronidase‐responsive charge reversal property, while MTO‐Cu endows this nanoadjuvant with pH/GSH dual‐responsive release behavior. Therefore, CS/MTO‐Cu@AMI efficiently sensitizes chemotherapy and activates systemic antitumor immunity in vitro and in vivo, providing an innovative solution to potentiate cancer chemo‐immunotherapy.

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Front-line chemo-immunotherapy is not inferior to ibrutinib in CLL

Cited by 2 publications

References 6 publications

Diagnosis, treatment and supportive management of chronic lymphocytic leukemia: recommendations of the Dutch HOVON CLL working group

Diagnosis, treatment and supportive management of chronic lymphocytic leukemia: recommendations of the Dutch HOVON CLL working group

Clinical Chemotherapeutic Agent Coordinated Copper‐Based Nanoadjuvants for Efficiently Sensitizing Cancer Chemo‐Immunotherapy by Cuproptosis‐Mediated Mitochondrial Metabolic Reprogramming

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