BCR and rheumatoid arthritis: R406 is the first BCR signaling agent that was shown to be active in CLL.73 This compound was initially developed as potential treatment for allergy and rheumatoid arthritis, because of its capacity to inhibit signaling through FcɛRI and Fcγ receptors.74 Early trials of fostamatinib in patients with rheumatoid arthritis showed clinical activity and potent anti-inflammatory effects.75,76 Subsequently, fostamatinib was tested in a phase 1/2 trial of relapsed or refractory NHL and CLL.77 In the phase 1 part of the trial a dose of 200mg p.o. bid was established.