Faculty Collaboration Database

Safety and activity of BTK inhibitor ibrutinib combined with ofatumumab in chronic lymphocytic leukemia: a phase 1b/2 study. Blood 2015 Aug 13;126(7):842-50

Date

06/28/2015

Pubmed ID

26116658

Pubmed Central ID

PMC4536539

DOI

10.1182/blood-2014-12-617522

Scopus ID

2-s2.0-84940063235 (requires institutional sign-in at Scopus site)   116 Citations

Abstract

Ibrutinib represents a therapeutic advance in chronic lymphocytic leukemia (CLL) but as monotherapy produces few complete remissions in previously treated patients. Anti-CD20 antibodies have improved response and progression-free survival (PFS) when combined with chemotherapy. We evaluated the safety and activity of adding ofatumumab to ibrutinib in 3 different administration sequences. Patients with CLL/small lymphocytic lymphoma (SLL), prolymphocytic leukemia, or Richter's transformation who failed ≥2 prior therapies were enrolled. Patients received ibrutinib 420 mg daily and 12 doses of ofatumumab 300/2000 mg in 3 schedules: ibrutinib lead-in (group 1; n = 27), concurrent start (group 2; n = 20), or ofatumumab lead-in (group 3; n = 24). Seventy-one patients were treated; most had high-risk disease including del(17)(p13.1) (44%) or del(11)(q22.3) (31%). The most frequent adverse events (any grade) were diarrhea (70%), infusion-related reaction (45%), and peripheral sensory neuropathy (44%). Overall response rates in CLL/SLL patients (n = 66) were 100%, 79%, and 71% in groups 1, 2, and 3, respectively. Estimated 12-month PFSs for all patients were 89%, 85%, and 75%, respectively. Four patients in group 3 progressed prior to receiving ibrutinib. This study demonstrates the tolerability and clinical activity of this combination with quicker time to best response than single-agent ibrutinib and with durable responses. This trial was registered at www.clinicaltrials.gov as #NCT01217749.

Author List

Jaglowski SM, Jones JA, Nagar V, Flynn JM, Andritsos LA, Maddocks KJ, Woyach JA, Blum KA, Grever MR, Smucker K, Ruppert AS, Heerema NA, Lozanski G, Stefanos M, Munneke B, West JS, Neuenburg JK, James DF, Hall N, Johnson AJ, Byrd JC

Author

Samantha M. Jaglowski MD, MPH Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenine
Aged
Aged, 80 and over
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols
Disease-Free Survival
Drug Administration Schedule
Female
Humans
Kaplan-Meier Estimate
Leukemia, Lymphocytic, Chronic, B-Cell
Male
Middle Aged
Piperidines
Protein Kinase Inhibitors
Protein-Tyrosine Kinases
Pyrazoles
Pyrimidines
Treatment Outcome