ORLANDO ­– Obinutuzumab monotherapy for 1 cycle followed by venetoclax and obinutuzumab in previously untreated, elderly patients with chronic lymphocytic leukemia (CLL) and comorbidities seems tolerable, a study presented at the American Society of Hematology  57th Annual Meeting has shown.1

“Initiating treatment with obinutuzumab followed by venetoclax appears tolerable in this population,” said study lead and presenter Kirsten Fischer, MD, of the University Hospital Cologne Center of Integrated Oncology Cologne-Bonn in Cologne, Germany.

The prospective, open-label, multicenter, randomized, phase 3 CLL14 trial was designed to evaluate the efficacy and safety of obinutuzumab, a type 2, glycoengineered anti-CD20-antibody, and venetoclax compared with obinutuzumab plus chlorambucil in previously untreated patients with CLL and coexisting medical conditions; however, a safety run-in phase was performed first to assess the tolerability of obinutuzumab plus venetoclax.

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A total of 13 previously untreated patents aged 59 to 88 years were enrolled. All patients received 6 cycles of obinutuzumab and venetoclax followed by 6 additional cycles of venetoclax alone. Obinutuzumab was administered intravenously at a dose of 100 mg on day 1; 900 mg on day 2 (or 1000 mg on day 1); 1000 mg on days 8 and 15 of cycle 1; and 1000 mg on day 1 for cycles 2 through 6. Venetoclax was dose-escalated gradually weekly from 20 mg to 400 mg starting at day 22 of cycle 1. Patients were also assessed for tumor lysis syndrome risk.

“At the time of data cut-off, all but 1 patients had completed the 6 cycles of combination therapy,” Dr Fischer noted.

Results showed all patients experienced at least 1 adverse event with 69.2% of patients experiencing at least 1 grade 3 or 4 adverse event.

The most common adverse events were infusion-related reactions, neutropenia, diarrhea, hyperkalemia, infection, cough, dizziness, hyperglycemia, hypotension, nausea, pyrexia, syncope, thrombocytopenia, tumor lysis syndrome, bradycardia, leukopenia, and increased transaminases.

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The most common grade 3 to 4 adverse events were infusion-related reactions, neutropenia, infection, syncope, thrombocytopenia, tumor lysis syndrome, hyperglycemia, pyrexia, bradycardia, leukopenia, and elevated transaminases. Grade 3 or 4 tumor lysis syndrome or neutropenia experienced by patients resulted in treatment modification.

Dr Fischer also presented preliminary efficacy data from 12 patients, which showed that there had been reduction in lymphadenopathy and lymphocyte counts. The overall response rate was 100% after 6 cycles of therapy. Complete responses could not be differentiated and are therefore classified as partial responses only.

“Preliminary efficacy data appear promising,” Dr Fischer concluded. “Based on the IMDC review of the safety data, the randomized phase has started enrolling.”


  1. Fischer K, Fink A-M, Bishop H, et al. Results of the safety run-in phase of CLL14 (BO25323): a prospective, open-label, multicenter randomized phase III trial to compare the efficacy and safety of obinutuzumab and venetoclax (GDC-0199/ABT-199) with obinutuzumab and chlorambucil in patients with previously untreated CLL and coexisting medical conditions. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.