purging with chlorambucil to prevent infusion-related before obinutuzumab administration . a monocentric pilot experience

Obinutuzumab (GA101; G) is a glycoengineered type II anti-CD20 monoclonal antibody with an enhanced affinity for the FcγRIIIa receptor on effector cells and thus enhanced antibody-dependent cell-mediated cytotoxicity (ADCC)1. Its efficacy and safety in combination with chlorambucil (Chl) in patients with treatment-naïve chronic lymphocytic leukemia (CLL) and comorbidities were demonstrated in the CLL11 study by improved progression-free survival (PFS) and overall survival (OS) compared with Chl plus rituximab (R) or Chl alone2, 3, leading to the FDA approval for its use in combination with Chl in patients with previously untreated CLL in 2013. Then the GREEN trial proved the safety and tolerability of G, administered in untreated and relapsed or refractory patients, both fit and unfit, alone, or combined with chemotherapy4. Nevertheless, it has emerged that the infusion of G was burdened by a high incidence of infusion-related reactions (IRRs). IRRs are among the worst complications of frontline G-Chl treatment to deal with in urgency, complicating collectively up to 87% of the infusions (grades 1-2 67%, grades 3-4 20%)2. Considering that the Chl dose used in CLL11 has been lower than its use in association with R in other European experiences5, 6 and that G could be used in unfit untreated patients with Chl without mention of the Chl schedule, we explored the possibility to use the same schedule of G-Chl adding 2 cycles of Chl as purging therapy before G as previously published by several groups in association with R5-8. The primary objectives of our pilot study were the toxicity and efficacy of Chl 1 mg/kg for each 28-day cycle, administered at a standard daily dose of 10 mg until the predetermined dose was reached for a total of 8 cycles with 2 cycles of purging before the start of the G administration7, 8. G was infused intravenously from the third cycle onwards at standard dose as reported by Goede's study2. Patients performed complete blood count (CBC) and immunochemical analysis before every cycle.