Laurie H. Sehn, MD, MPH: The GADOLIN trial was a randomized phase III trial comparing obinutuzumab and bendamustine versus bendamustine alone in patients who are known to be rituximab refractory with relapsed/refractory follicular lymphoma. And the final analysis demonstrates that the original finding—that the combination of obinutuzumab-bendamustine led to a marked improvement in outcome, with about 43% reduction in the risk of progression or death. And the overall survival benefit that was seen initially reported has been sustained over time. Clearly the addition of obinutuzumab in this rituximab-refractory combination really leads to an important improvement survival in these patients who can be difficult to get into durable control.

Scott Huntington, MD, MPH, MSc: At last year’s ASH [American Society of Hematology Annual Meeting & Exposition], the GADOLIN data, longer-term follow-up was presented. If you recall, this trial compared bendamustine alone versus bendamustine plus obinutuzumab in a relapsed/refractory setting. Patients had to be refractory to rituximab to enroll in the study, and the updated data set suggests that the continued bendamustine and obinutuzumab is favorable over bendamustine alone. In terms of whether this changed practice, most of us would consider bendamustine alone as a suboptimal second-line regimen. But it does suggest that obinutuzumab combined with bendamustine does have a role in the second- or later-line setting.

In terms of efficacy, there was about a doubling of progression-free survival [PFS]. Bendamustine led to about a 13-month improvement of PFS, versus about 24 months in the obinutuzumab-bendamustine arm. There was a toxicity that we typically would expect with a combined CD20 antibody with bendamustine, including things like cytopenias and infections. But generally, no increased signal or no new safety signals during the long-term follow-up.

Bendamustine combined with obinutuzumab is clearly a reasonable choice for patients with advanced-stage disease as long as they have a nice response to immunochemotherapy in the first-line setting. This data establish that the PFS benefit continues with obinutuzumab compared with bendamustine alone, and there were no new safety signals of concern. And so it clearly is a reasonable choice, and this was a welcomed update.

There’s been a number of recent investigations of combining obinutuzumab alongside novel therapies, including lenalidomide. In the GADOLIN study, which was a multicenter study out of Italy, patients in the relapsed/refractory setting received obinutuzumab along with lenalidomide. Initially had a low lenalidomide dosage of about 20 mg/day, 3 weeks out of 4, for the first 6 months.

Patients could then decrease their lenalidomide dosage to about 10 mg for the remainder of another year and receive the obinutuzumab for the remainder of about 30 months. In the relapsed/refractory setting, the combination of obinutuzumab-lenalidomide had good efficacy. There was progression-free survival of about 30 months, and the combination looked quite compelling. There were potential toxicities that we might expect combining obinutuzumab with lenalidomide, including things like cytopenias and some need of growth factor at some point. But generally, it was well tolerated and compares favorably to the rituximab-and-lenalidomide history.

In terms of going forward I think it will be warranted to randomize this trial to have both a rituximab-containing arm in lenalidomide compared with obinutuzumab, and lenalidomide to assess the true efficacy of the addition of obinutuzumab, as well as the safety difference between these 2 new compounds.

At this point when I see a patient, I am typically using rituximab in the first-line setting. We’ve talked about the overall survival similarity between obinutuzumab and rituximab, and often we’ll think about using obinutuzumab in the second-line setting, whether it’s combined with, say, bendamustine or combined with CHOP [cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone]. That is typically where I’m using obinutuzumab: in the second-line setting in someone who had progression beyond rituximab containing immunochemotherapy.

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