The GALLIUM Study in Follicular Lymphoma

Transcript: Alexey V. Danilov, MD, PhD: The GALLIUM study is a randomized phase III clinical trial sponsored by Genentech, which randomized 1200 patients with follicular lymphoma. Those patients with follicular lymphoma had advanced stage—stage III/IV—disease. However, patients with stage II disease who had bulky lymphadenopathy—over 7-cm lymph nodes—were also enrolled. Six hundred patients were randomized to each arm, with 1200 patients total, and patients received chemotherapy, either in combination with rituximab or a second-generation glycoengineered CD20 antibody, obinutuzumab. The primary endpoint on the study was progression-free survival, and the primary endpoint was actually met. Overall, after about 6 years of follow-up, patients achieved responses at the end of induction therapy at roughly the same rate. The overall response rate was similar in the G-CHOP [obinutuzumab, cyclophosphamide, doxorubicin, vincristine, prednisone] arm versus the R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] arm at the end of induction. However, progression-free survival was longer in patients who received the obinutuzumab-CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] combination. This was first reported a couple of years ago, after a roughly 3-year follow-up, and was again confirmed after 50 months.

Another point that this analysis has confirmed is that patients who received obinutuzumab in combination with chemotherapy—either CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone], CVP [cyclophosphamide, vincristine, prednisone], or bendamustine— had a somewhat high risk of infectious complications, at least numerically. A lot of those combinations did happen during the maintenance phase; therefore it still remains a question which treatment is better. If you look at progression-free survival in isolation in patients who received chemotherapy with CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone], bendamustine, or CVP [cyclophosphamide, vincristine, prednisone], obinutuzumab does yield an advantage over rituximab.

Another important point to make is that overall survival has not improved so far in patients who were treated with obinutuzumab over rituximab. That remains the same in both arms of the study.

Carla Casulo, MD: The GALLIUM study randomized patients with follicular lymphoma to obinutuzumab-containing chemotherapy or rituximab-containing chemotherapy. Obinutuzumab is an anti-CD20 antibody. It is very similar to rituximab, but it binds complement less effectively, and it enhances antibody-dependent cytotoxicity. Those are the 2 differences, broadly, between rituximab and obinutuzumab.

Obinutuzumab has been looked at to see whether it was, perhaps, more effective than rituximab in this large study. The study randomized patients to those 2 arms. It was a multicenter study, so the chemotherapy of choice was picked by the site in advance, and the randomization was the antibody.

That was 6 to 8 cycles of antibody with chemotherapy and then 2 years of maintenance. That was a big randomized, international study, and the primary endpoint was progression-free survival.

The initial results were presented at ASH [American Society of Hematology Annual Meeting] in 2017 and published in the New England Journal of Medicine later on. A 4-year follow-up from this past ASH showed us that, in a longer follow-up, essentially, the results were sustained. There was an ongoing benefit to obinutuzumab in terms of progression-free survival. The initial study showed a 7% benefit in progression-free survival when using obinutuzumab.

What the study from 2018 showed is that the results were maintained. The progression-free survival benefit still persists, but there is no benefit to overall survival. Given that the follow-up is only 5 years, you’re not going to demonstrate a benefit in overall survival in follicular lymphoma with such short follow-up. I think, over time, we will know whether or not that ends up providing a survival benefit. But for now, we see that there is still a sustained progression-free survival benefit.

Transcript Edited for Clarity