Obinutuzumab Plus Chemotherapy Lengthens PFS in Follicular Lymphoma

SAN DIEGO-Induction with obinutuzumab plus chemotherapy and maintenance is superior to rituximab plus chemotherapy and maintenance in patients with previously untreated advanced follicular lymphoma, according to a study (abstract 6) presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition, held December 3–6.

“Obinutuzumab-based therapy significantly improves outcomes compared to rituximab-based therapy and should now be considered as a first-line treatment for follicular lymphoma,” said lead author Robert E. Marcus, MBBS, of Kings College Hospital in London.

Marcus presented the primary results of a global, open-label, randomized, phase III trial to compare the efficacy of these two anti-CD20 monoclonal antibodies. The study evaluated the efficacy and safety of either drug plus chemotherapy (institutional choice of bendamustine, CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisolone], or CVP [cyclophosphamide, vincristine, and prednisolone]) followed by maintenance with the same drug as first-line treatment in 1,202 untreated follicular lymphoma patients, with 601 patients in each arm.

Patients had grade 1 to 3a disease, and an ECOG performance status up to 2. Most of the patients (median age, 59 years) had aggressive disease. Treatment arms were well balanced by disease stage and prognostic factors. Most of the patients received bendamustine (57.1%); 33.1% received CHOP and 9.8% received CVP. All patients received 2 years of maintenance therapy.

After a median follow-up of 34.5 months, the 3-year progression-free survival (PFS) rate (the primary endpoint) was 80% with obinutuzumab and 73.3% with rituximab. “There was a 34% reduction in the risk of progression or death with obinutuzumab as compared to rituximab. This improvement would translate to a 1.5-times longer median PFS for obinutuzumab-chemotherapy than rituximab-chemotherapy,” said Marcus.

The 3-year time-to-next therapy was higher with obinutuzumab (87.1%) compared with rituximab (81.1%). There was no difference in overall survival.

In the obinutuzumab arm, 92% of patients achieved minimal residual disease negativity in the blood and/or bone marrow, compared with 84.9% of patients in the rituximab arm.

Safety data show a slightly higher rate of infusion reactions with obinutuzumab vs rituximab and a higher incidence of fatal adverse events, with about a 4% higher rate of non–lymphoma-related mortality in the obinutuzumab arm, mostly in patients receiving bendamustine. Grade 5 fatalities were higher than expected in induction treatments in follicular lymphoma.

Frequency of cytopenias and infections was higher with obinutuzumab. Febrile neutropenia was slightly higher in the obinutuzumab arm (6.9%) than the rituximab arm (4.9%).

Adverse events led to treatment discontinuation in 16.3% of patients taking obinutuzumab and 14.2% of patients taking rituximab in the absence of disease progression.

There was also a small signal for secondary malignancies in both arms.

“Clinicians need to decide whether safety issues outweigh the benefits in PFS,” said Marcus. He noted that all patients benefited whether they received bendamustine, CHOP, or CVP.

“The clinically meaningful improvements in PFS were supported by other time-dependent endpoints,” noted Marcus. He warned clinicians to take precautions when using bendamustine due to risk of infection.

Marcus and colleagues do not believe the difference in dosing between obinutuzumab and rituximab affected outcomes, and no data suggest that increased rituximab dosage leads to improved efficacy.