Ibrutinib: searching for a partner drug
Mené sur 229 patients atteints d'une leucémie lymphocytaire chronique, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout de l'ibrutinib et du chlorambucile à l'obinutuzumab en traitement de première ligne (durée médiane de suivi : 31,3 mois)
Although ibrutinib has become the treatment of choice for patients with relapsed or refractory chronic lymphocytic leukaemia, its position as a first-line regimen is less clear. As ibrutinib prevents homing and migration of leukaemic cells to their microenvironmental niche, it induces quiescence but not apoptosis of chronic lymphocytic leukaemia cells. As a consequence, complete responses are rare and require a prolonged duration of treatment with concomitant high costs, toxicities and side-effects, and the risk of selecting resistant clones. For these reasons, and because of its high tolerability and long progression-free survival and overall survival, many physicians still prefer a 6-month regimen of chlorambucil plus obinutuzumab for elderly patients. Improvement of ibrutinib-based therapy can therefore be achieved by reducing side-effects or achieving deep remissions that allow treatment cessation, thereby potentially decreasing the development of resistance. To achieve these desired effects, ibrutinib needs a partner drug. Logical as it sounds, simultaneously combining ibrutinib with rituximab has not shown a progression-free survival benefit, which might be related to the in-vitro observation that ibrutinib inhibits antibody-dependent cellular cytotoxicity. 7 Obinutuzumab might be a more effective alternative because of its higher potency in inducing this cytotoxicity in the presence of ibrutinib.
The Lancet Oncology 2018