A phase 1b/2 study evaluating activity and tolerability of the BTK inhibitor ibrutinib in combination with ofatumumab in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and related diseases.
2014; Lippincott Williams & Wilkins; Volume: 32; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2014.32.15_suppl.7009
ISSN1527-7755
AutoresSamantha Jaglowski, Jeffrey A. Jones, Joseph M. Flynn, Leslie A. Andritsos, Kami J. Maddocks, Jennifer A. Woyach, Kristie A. Blum, Michael R. Grever, Susan M. Geyer, Nyla A. Heerema, Gerard Lozanski, Mona Stefanos, Nathan C. Hall, Veena Nagar, Brian Munneke, Jamie-Sue West, Jutta K. Neuenburg, Danelle F. James, Amy J. Johnson, John C. Byrd,
Tópico(s)Immunodeficiency and Autoimmune Disorders
Resumo7009 Background: Ibrutinib (Ib), an oral covalent BTK inhibitor, has significant activity in relapsed/refractory (R/R) CLL. Adding ofatumumab (O), an anti-CD20 antibody, to chemotherapy in CLL can improve response and progression free survival (PFS). Here, Ib was given with O in 3 different administration sequences. Methods: Patients (pts) with R/R CLL/SLL, PLL or Richter’s transformation (RT) after ≥2 prior therapies including a purine analog were treated with 420 mg Ib daily and 300/2000 mg O (8 x weekly/then 4 x monthly) in 28-day cycles until progressive disease (PD). Group (G) 1 had 1 cycle of Ib monotherapy, then O was added. G2 started O on Day (D) 1/Cycle (C) 1 and Ib on D2/C1. G3 had 2 cycles of O monotherapy, then Ib was added on D1/C3. Results: 71 pts (27, 20, 24 in G1, 2, 3) were enrolled. Median age was 64 y; 61% had Rai stage III/IV; 65 pts had CLL, 1 SLL, 2 PLL and 3 RT; 75% had lymph nodes ≥5 cm; 44% had del(17p); 31% had del(11q). The most frequent AEs were diarrhea (68%), infusion-related reaction (IRR, 45%), peripheral sensory neuropathy (42%) and stomatitis (37%). In all, 61% had ≥1 AE ≥grade (g) 3; most common g 3-4 AE was neutropenia in 17%. 39% had SAEs including: 1 pt in G2 with ≥g 3 IRR; 6 pts with AEs leading to Ib discontinuation; 9 pts died within 30 days of last dose and 2 within f/u period. Overall response rate in CLL/SLL was 100% in G1, 79% in G2, and 71% in G3. 2 additional pts achieved a partial response with lymphocytosis. 4 pts in G3 progressed before starting Ib. At study end, 52/58 responders (90%) remained progression-free with f/u of 16, 12 and 11 months for G1, 2 and 3, respectively. Three RT pts had disease control followed by PD on Day 471, 168, and 137. At 12 months, PFS was 89%, 85%, and 90% in G1, 2 and 3, respectively; 76% continued on Ib in a long-term extension study; 2 pts had a transplant. Conclusions: Ib combined with O is well tolerated and highly active (83% ORR) in pts with R/R CLL/SLL in all 3 dosing sequences investigated. Because of these compelling results, randomized trials evaluating anti-CD20 antibodies in combination with Ib with a PFS endpoint are ongoing. Clinical trial information: NCT01217749.
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