Acalabrutinib monotherapy in patients with Richter transformation
Mené dans 4 pays sur 25 patients atteints d'une leucémie lymphoïde chronique s'étant transformée en lymphome à grandes cellules B (syndrome de Richter), cet essai de phase I/II évalue la dose maximale tolérée de l'acalabrutinib en monothérapie et analyse ses caractéristiques pharmacocinétiques, puis évalue son efficacité, du point de vue du taux de réponse globale, de la durée de la réponse et de la survie sans progression
Richter transformation describes the development of an aggressive lymphoma, predominantlydiffuse large B-cell lymphoma but also Hodgkin lymphoma in patients with underlyingchronic lymphocytic leukaemia. The incidence of histologically confirmed Richter transformation is low, varyingbetween 2% and 10% in patients diagnosed with chronic lymphocytic leukaemia. Among the known risk factors for the development of Richter transformation are TP53 aberrations or NOTCH1 mutations, and the majority of transformations occur in heavily pre-treated patients,although up to a third of cases occur in previously untreated patients with chroniclymphocytic leukaemia. Richter transformation is characterised by poor median overall survival of 6–8 months. Most available treatment approaches have not translated into median progression-freesurvival better than 10–16 months, and resulted in little improvement in overall survival(appendix). Although the genetics of diffuse large B-cell lymphoma Richter transformation canbe divergent from de-novo diffuse large B-cell lymphoma,treatment approaches comprise therapies for de-novo diffuse large B-cell lymphomawith chemoimmunotherapy such as R-CHOP (rituximab, cyclophosphamide, doxorubicin,vincristine, prednisone). For fit patients who respond to chemoimmunotherapy, consolidation with autologousor allogeneic haematopoietic stem-cell transplantation can yield curative potential. More recently, targeted agents such as the BCL-2 inhibitor venetoclax or a continuousBruton's tyrosine kinase (BTK) inhibitor with or without an anti-CD20 antibody havebeen investigated in clinical trials.
The Lancet Haematology , 2021