The Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, with chemoimmunotherapy in patients with chronic lymphocytic leukemia
Mené sur 33 patients atteints d'une leucémie lymphocytaire chronique récidivante/réfractaire, cet essai de phase Ib évalue la toxicité et l'activité antitumorale de l'ibrutinib en combinaison avec une chimio-immunothérapie (bendamustine-rituximab ou fludarabine-cyclophosphamide-rituximab)
The safety and efficacy of ibrutinib, an oral inhibitor of Bruton's tyrosine kinase, were evaluated in combination with chemoimmunotherapy (CIT) in a multicenter, phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to six 28-day cycles with continuous daily ibrutinib 420 mg until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously-treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was consistent with that expected from either CIT or single-agent ibrutinib. The objective response rate (ORR) with BR-ibrutinib was 93.3%, including 16.7% complete responses (CRs) initially, that increased to 40.0% with the extension period; including 1 patient with partial response with lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and 70.3% remained progression free, respectively. All 3 patients treated with ibrutinib-FCR are in CR. Ibrutinib may enhance CIT efficacy without additive toxicities, providing the rationale for investigation of this combination in an ongoing phase 3 trial. The study is registered to www.clinicaltrials.gov as NCT01292135.