Obinutuzumab in combination with lenalidomide in relapsed/refractory follicular lymphoma – results of an open-label, multicenter, phase Ib study

Franck Morschhauser from the Centre Hospitalier Régional Universitaire de Lille, Lille, France, and colleagues conducted an open-label, multicenter, phase Ib study (NCT01582776) investigating obinutuzumab, a type II anti-CD20 monoclonal antibody, in combination with lenalidomide for the treatment of patients with relapsed/refractory (R/R) follicular B-cell lymphoma (FL). The primary endpoint was to establish the maximum tolerated dose (MTD). Secondary endpoints were to evaluate the safety, efficacy, and tolerability of lenalidomide plus a fixed dose of obinutuzumab. On 1 August 2018, the results of the study were published ahead of print in Blood.

Patient characteristics:

• N = 20 patients were enrolled
• Median age: 61.5 years (range, 39–80)
• Median number of prior treatments: 2 (range, 1–5)
• Lenalidomide was administered at a dose of 10mg [n = 7], 15mg [n = 3], 20mg [n = 6], and 25 mg [n = 3] on days 1-21 (cycle 1) and on days 2-22 (cycles 2-6) in 28-day cycles
• Obinutuzumab was administered at a dose of 1000 mg IV on days 8, 15, and 22 (cycle 1) and on day 1 (cycles 2–6)

Key findings:

• N = 19 patients were evaluable to assess safety and efficacy
• Dose limiting toxicities (DLTs)
  • Four DLTs were observed in 2 patients, which were not treatment related
  • MTD was not reached
  • Recommended phase II dose based on the safety profile: 20 mg lenalidomide
• Safety
  • The most common adverse events (AEs) included constipation (52.6%), neutropenia (47.4%), and asthenia (36.8%)
  • 3% (9/14) of the grade 3/4 AEs were neutropenia, no febrile neutropenia was observed
  • 6% of patients (6/19) died
• Efficacy
  • Overall response rate: 63.2% (95% CI, 38.4–83.7)
  • Complete remission was reached in 8 patients
  • Unconfirmed complete remission was reached in 3 patients
  • Partial response was observed in one patient
  • 3-year progression-free survival: 52.1% (95% CI, 28.0–71.6)
  • 3-year duration of response: 68.4% (95% CI, 35.9–86.8)
  • 3-year overall survival: 73.3% (95% CI, 47.2–87.9)

Taken together, this study indicates that lenalidomide in combination with obinutuzumab is safe and efficient in patients with relapsed or refractory follicular lymphoma. The recommended phase II dose of lenalidomide was assessed at a dose of 20 mg. The phase II portion of this study is evaluating efficacy of this combination regimen.