Safety and efficacy of obinutuzumab with CHOP or bendamustine in previously untreated follicular lymphoma

Abstract

The GAUDI study assessed safety and preliminary efficacy of induction therapy with obinutuzumab plus chemotherapy, followed by maintenance therapy with obinutuzumab alone, in previously untreated patients with follicular lymphoma. Assignment to chemotherapy was decided on a per-center basis before the patients' enrollment. Patients (n=81) received four to six cycles of obinutuzumab plus bendamustine every 4 weeks or six to eight cycles of obinutuzumab plus CHOP every 3 weeks. Patients with an end-of-treatment response were eligible for obinutuzumab maintenance therapy every 3 months for 2 years or until disease progression. Induction treatment was completed by 90% of patients in the obinutuzumab plus bendamustine group and 95% in the obinutuzumab plus CHOP group, while maintenance was completed by 81% and 72% of patients, respectively. All patients experienced at least one adverse event during induction, most commonly infusion-related reactions (58%), the majority of which were grade 1/2. The most common hematologic adverse event was grade 3/4 neutropenia (36% during induction and 7% during maintenance). One treatment-related death occurred during the maintenance phase. At the end of induction, 94% of patients had achieved an overall response, with complete response based on computed tomography in 36%. The progression-free survival rate at 36 months was 90% in the obinutuzumab plus bendamustine group and 84% in the obinutuzumab plus CHOP group. These results demonstrate that induction therapy with obinutuzumab plus bendamustine or obinutuzumab plus CHOP, followed by obinutuzumab maintenance, is associated with tolerable safety and promising efficacy. This study is registered at ClinicalTrials.gov as NCT00825149.

Figure 1.

Disposition of patients in the study. *Reasons for discontinuation from G-B induction therapy: insufficient therapeutic response (n=2), administrative/other (n=1), and withdrawal of consent (n=1; this patient did not enter post-induction follow-up). †Reasons for discontinuation from G-CHOP induction therapy: adverse event (AE)/intercurrent illness (n=1) and administrative/other (n=1). ^‡Reasons patients did not start G-maintenance treatment (G-B group): AE/intercurrent illness (n=1). ^§Reasons patients did not start G-maintenance treatment (G-CHOP group): administrative/other (n=2). ^IReasons for withdrawal from maintenance treatment (G-B group): AE/intercurrent illness (n=5) and insufficient therapeutic response (n=2). ^¶Reasons for withdrawal from maintenance treatment (G-CHOP group): AE/intercurrent illness (n=4), insufficient therapeutic response (n=3), administrative/other (n=2), and death (n=1).

Figure 2.

Progression-free survival. Progression-free survival (PFS) for (A) the total study population, the (B) G-B group, and (C) the G-CHOP group. G-B: obinutuzumab plus bendamustine; G-CHOP: obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

Figure 3.

Mean serum concentration of obinutuzumab throughout the induction and maintenance periods. G-B: obinutuzumab plus bendamustine; G-CHOP: obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

Figure 4.

B-cell levels throughout the induction and maintenance periods. BSL: baseline; EoT: end of treatment; G-B: obinutuzumab plus bendamustine; G-CHOP: obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.