Obinutuzumab alone or in combination with cytotoxic agents used in front-line therapy

A prospective randomized trial (NCT01332968) of 1,202 patients with previously untreated follicular lymphoma compared obinutuzumab combined with bendamustine (50%), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (33%), or CVP (cyclophosphamide, vincristine, and prednisone) (10%) with rituximab combined with the same chemotherapy regimens (based on investigator choice).[54] After six cycles of combination therapy, patients had 2 years of maintenance therapy, receiving the same antibody every 2 months.Several issues have been raised about this study:In summary, in the absence of any change in OS, switching from rituximab to obinutuzumab in combination with chemotherapy for previously untreated follicular lymphoma is a difficult choice. The PFS differences may be attributable to the imbalance in monoclonal antibody dosing, and the increased side effects and costs are mitigating factors. In this trial, bendamustine combined with either antibody led to unacceptable rates of toxic death.

A prospective randomized trial (NCT01332968) of 1,202 patients with previously untreated follicular lymphoma compared obinutuzumab combined with bendamustine (50%), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (33%), or CVP (cyclophosphamide, vincristine, and prednisone) (10%) with rituximab combined with the same chemotherapy regimens (based on investigator choice).[54] After six cycles of combination therapy, patients had 2 years of maintenance therapy, receiving the same antibody every 2 months.Several issues have been raised about this study:In summary, in the absence of any change in OS, switching from rituximab to obinutuzumab in combination with chemotherapy for previously untreated follicular lymphoma is a difficult choice. The PFS differences may be attributable to the imbalance in monoclonal antibody dosing, and the increased side effects and costs are mitigating factors. In this trial, bendamustine combined with either antibody led to unacceptable rates of toxic death.

With a median follow-up of 34.5 months, the 3-year PFS rate was 80% in the obinutuzumab group and 73.3% in the rituximab group (HR, 0.66; 95% CI, 0.51–0.85; P = .001).[54][Level of evidence B1]

A prospective randomized trial (NCT01332968) of 1,202 patients with previously untreated follicular lymphoma compared obinutuzumab combined with bendamustine (50%), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (33%), or CVP (cyclophosphamide, vincristine, and prednisone) (10%) with rituximab combined with the same chemotherapy regimens (based on investigator choice).[54] After six cycles of combination therapy, patients had 2 years of maintenance therapy, receiving the same antibody every 2 months.Several issues have been raised about this study:In summary, in the absence of any change in OS, switching from rituximab to obinutuzumab in combination with chemotherapy for previously untreated follicular lymphoma is a difficult choice. The PFS differences may be attributable to the imbalance in monoclonal antibody dosing, and the increased side effects and costs are mitigating factors. In this trial, bendamustine combined with either antibody led to unacceptable rates of toxic death.

There was no difference in OS.

A prospective randomized trial (NCT01332968) of 1,202 patients with previously untreated follicular lymphoma compared obinutuzumab combined with bendamustine (50%), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (33%), or CVP (cyclophosphamide, vincristine, and prednisone) (10%) with rituximab combined with the same chemotherapy regimens (based on investigator choice).[54] After six cycles of combination therapy, patients had 2 years of maintenance therapy, receiving the same antibody every 2 months.Several issues have been raised about this study:In summary, in the absence of any change in OS, switching from rituximab to obinutuzumab in combination with chemotherapy for previously untreated follicular lymphoma is a difficult choice. The PFS differences may be attributable to the imbalance in monoclonal antibody dosing, and the increased side effects and costs are mitigating factors. In this trial, bendamustine combined with either antibody led to unacceptable rates of toxic death.

Compared with what has been seen historically, there was a high rate of toxic deaths among patients using bendamustine in the obinutuzumab arm (5.6%) and in the rituximab arm (4.4%). For patients with indolent low-grade lymphoma, with median survivals exceeding 15 years, the number of toxic deaths during first-line therapy seems excessive. By comparison, the toxic death rate was 1% to 2% when either antibody was combined with CHOP or CVP.

A prospective randomized trial (NCT01332968) of 1,202 patients with previously untreated follicular lymphoma compared obinutuzumab combined with bendamustine (50%), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (33%), or CVP (cyclophosphamide, vincristine, and prednisone) (10%) with rituximab combined with the same chemotherapy regimens (based on investigator choice).[54] After six cycles of combination therapy, patients had 2 years of maintenance therapy, receiving the same antibody every 2 months.Several issues have been raised about this study:In summary, in the absence of any change in OS, switching from rituximab to obinutuzumab in combination with chemotherapy for previously untreated follicular lymphoma is a difficult choice. The PFS differences may be attributable to the imbalance in monoclonal antibody dosing, and the increased side effects and costs are mitigating factors. In this trial, bendamustine combined with either antibody led to unacceptable rates of toxic death.

The side effects were significantly higher with obinutuzumab in terms of infusion reactions and subsequent adverse events.

A prospective randomized trial (NCT01332968) of 1,202 patients with previously untreated follicular lymphoma compared obinutuzumab combined with bendamustine (50%), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (33%), or CVP (cyclophosphamide, vincristine, and prednisone) (10%) with rituximab combined with the same chemotherapy regimens (based on investigator choice).[54] After six cycles of combination therapy, patients had 2 years of maintenance therapy, receiving the same antibody every 2 months.Several issues have been raised about this study:In summary, in the absence of any change in OS, switching from rituximab to obinutuzumab in combination with chemotherapy for previously untreated follicular lymphoma is a difficult choice. The PFS differences may be attributable to the imbalance in monoclonal antibody dosing, and the increased side effects and costs are mitigating factors. In this trial, bendamustine combined with either antibody led to unacceptable rates of toxic death.

Obinutuzumab costs significantly more than rituximab.