Ibrutinib and R-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma of non-GCB type: Phase II clinical trial of the Spanish GELTAMO group
Mené sur 64 patients atteints d'un lymphome diffus à grandes cellules B de type "non GCB" réfractaire ou récidivant, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité d'un traitement d'induction combinant ibrutinib et chimiothérapie de type R-GemOx (rituximab, gemcitabine et oxaliplatine) suivi d'un traitement d'entretien par ibrutinib
Purpose: This phase II clinical trial evaluated the combination of Ibrutinib with rituximab, gemcitabine and oxaliplatin (R-GemOx) in patients with non-germinal centre B-cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods: The IBDCL trial (NCT02692248) included patients with histological diagnosis of non-GCB DLBCL with relapsed or refractory disease and non-candidates for stem cell transplantation. Patients received an induction treatment consisting of 6 or 8 cycles of R-GemOx at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. The primary objective was to evaluate the overall response rate (ORR) after 4 cycles. Results: Sixty-four patients were included, 72% of them refractory to the last regimen. The ORR and CR rate after the 4th cycle were 53% (95% confidence interval [CI], 41–65) and 34% (95% CI, 24–46), respectively. Twenty-four (37%) patients started maintenance and 7 (11%) completed the planned 2 years. After a median follow-up of 29.7 months (range: 0.4-48.6), the estimated 2-year PFS and OS were 18% (95% CI, 8 – 28) and 26% (95% CI, 14 - 37), respectively. The most common grade ≥3 treatment-related adverse events (TRAEs) were thrombocytopenia (44%), neutropenia (30%) and anemia (14%). Grade ≥3 infectious and cardiovascular TRAEs were reported in 6 (9%) and 1 (2%) patient, respectively. Conclusions: Ibrutinib in combination with R-GemOx, followed by ibrutinib maintenance, demonstrated encouraging antitumor activity with durable responses and a manageable toxicity in patients with non-GCB DLBCL.