Evaluation of the novel therapeutic anti-CCR7 antibody CAP-100 as an add-on therapy in chronic lymphocytic leukemia patients receiving venetoclax.

The Bruton's tyrosine kinase inhibitor ibrutinib and the B-cell lymphoma 2 anti-apoptotic protein inhibitor venetoclax provide high response rates in chronic lymphocytic leukemia (CLL). However, there is a growing number of patients that relapse after treatment or show refractory disease, thus new targets and agents are still needed. We have previously reported the chemokine receptor CCR7 as a relevant deregulated target in CLL and have developed CAP-100, a novel therapeutic anti-CCR7 antibody that is under evaluation for relapse/refractory CLL (NCT04704323). While CCR7 expression has been shown to be down-modulated in CLL patients treated with ibrutinib, whether venetoclax acts in a similar manner remains unaddressed. Here, we aimed to document the impact of venetoclax on CCR7 expression in CLL cells, as well as on the pre-clinical activity of CAP-100. To this end, we addressed CCR7 expression by flow cytometry and the antibody efficacy by means of in vitro chemotactic and antibody-dependent cell-mediated cytotoxicity (ADCC) assays. Our data indicate that venetoclax treatment did not significantly modify CCR7 expression pattern nor CAP-100 mechanisms of action. Together, these findings support CAP-100 as an adjuvant therapy to venetoclax that may introduce additional modes of action in CLL therapy.

[Translated article] Consensus recommendations on the preventive treatment of migraine.

OBJECTIVE: The objectives are to know the opinion of neurologists and hospital pharmacists on those aspects still under debate regarding the role of anti-Calcitonin Gene-related Peptide monoclonal antibodies in the preventive treatment of migraine. To identify those controversies that still exist. To propose agreed recommendations for improvement of care. And to promote access of clinicians and patients to these new treatments in the prevention of migraine with biological drugs, in order to improve patient care and follow-up. METHODOLOGY: Recommendations for the use of biological drugs in the prevention of migraine were identified and evaluated through the Delphi consensus methodology, proposing 88 statements grouped into 3 themes: a clinical module that deals with the management of biological treatments in migraine; a patient module that discusses patient education and adherence improvement strategies; and a coordination module that includes statements related to strategies to improve joint work between the two groups. The 9-point Likert ordinal scale was used to score these recommendations and, subsequently, the data was statistically analysed through different metrics. RESULTS: After both rounds of voting, consensus was reached in agreement on 71 of the 88 statements (80.7%), leaving 1 statement (1.1%) with consensus in disagreement and 16 remaining as indeterminate (18.2%). CONCLUSIONS: The high degree of consensus indicates that the opinion of neurologists and hospital pharmacists on the role of anti-Calcitonin Gene-related Peptide monoclonal antibodies in the preventive treatment of migraine is very similar and allows identifying those controversies that still exist, to improve the care and follow-up of patients with migraine.

Consensus recommendations for the treatment of migraine prevention. / Recomendaciones de consenso para el tratamiento de la prevención de la migraña.

OBJECTIVE: The objectives are to know the opinion of neurologists and hospital pharmacists on those aspects still under debate regarding the role of anti-CGRP monoclonal antibodies in the preventive treatment of migraine. To identify those controversies that still exist. To propose agreed recommendations for improvement of care. And to promote access of clinicians and patients to these new treatments in the prevention of migraine with biological drugs, in order to improve patient care and follow-up. METHODOLOGY: Recommendations for the use of biological drugs in the prevention of migraine were identified and evaluated through the Delphi consensus methodology, proposing 88 statements grouped into three themes: a clinical module that deals with the management of biological treatments in migraine; a patient module that discusses patient education and adherence improvement strategies; and a coordination module that includes statements related to strategies to improve joint work between the two groups. The 9-point Likert ordinal scale was used to score these recommendations and, subsequently, the data was statistically analyzed through different metrics. RESULTS: After both rounds of voting, consensus was reached in agreement on 71 of the 88 statements (80.7%), leaving one statement (1.1%) with consensus in disagreement and 16 remaining as indeterminate (18.2%). CONCLUSIONS: The high degree of consensus indicates that the opinion of neurologists and hospital pharmacists on the role of anti-CGRP monoclonal antibodies in the treatment of migraine is very similar and allows identifying those controversies that still exist, to improve the care and follow-up of patients with migraine.