Cancer Conference Update: A Multimedia Review of Key Presentations from the 2016 American Society of Hematology Annual MeetingAbstract 6: GALLIUM Phase III study of obinutuzumab- versus rituximab-based induction and maintenance therapy for patients with previously untreated follicular lymphoma
6:59 minutes.
TRANSCRIPTION:
DR FLOWERS: So this is a very provocative study and one that potentially has an impact on the standard of care for patients with follicular lymphoma. In this trial they took a mixed group of patients with follicular lymphoma and patients with marginal zone lymphoma and allowed patients to receive chemotherapy of their choice by center for follicular lymphoma and by individual patient decision for patients with marginal zone lymphoma. And in all the major results that were presented at the plenary session were the results from the follicular lymphoma portion of this trial. In that portion there were more than 1,200 patients — so 1,202 patients in total — that were randomized to rituximab plus chemotherapy or obinutuzumab plus chemotherapy, with 601 patients in each group. This was a relatively younger patient population than the typical patient population with follicular lymphoma, but only slightly, so with a median age of 59 years in that patient population. When you look at the randomization of those 2 arms, there was a benefit for the group who received the so-called G chemo, or obinutuzumab plus chemotherapy when you compare the progression-free survival for those 2 patient populations. And that benefit amounted to about a hazard ratio of 0.66. So overall I think this looks to be a reasonably favorable result. I think there still are some questions about what this means in terms of anti-CD20 antibody. The patients who got obinutuzumab got a dose of 1,000 mg as a flat dose. And patients with rituximab received the typical dose of 375 mg/m2. I don't know that we’re going to ever answer this question about whether the dosing of anti-CD20 antibody or the efficacy of the anti-CD20 molecule really made the difference here, because we won’t have head-to-head trials that compare, presumably, equipotent doses of anti-CD20 antibody — for instance, using rituximab at a flat dose of 1,000 mg. But given the results that we have, these are provocative and meaningful improvement on rituximab plus chemotherapy, which has been the standard of care up to this point for newly diagnosed patients with follicular lymphoma that have more advanced-stage disease. DR LOVE: What about toxicity? DR FLOWERS: When you look at the toxicity, there was more toxicity in the group that received obinutuzumab. By and large, that toxicity is infusional-related toxicity with greater infusion-related reactions for patients who received obinutuzumab plus chemotherapy. There also was an increase in the cytopenias that were observed in that arm, with more neutropenia/thrombocytopenia in the group that received obinutuzumab plus chemotherapy. DR LOVE: But I guess it looked like the patients who had to come off therapy because of toxicity was about the same. DR FLOWERS: Correct. Yes. The patients who came off therapy because of toxicity was only about 16%, so relatively limited numbers of patients who were coming off because of toxicity. DR LOVE: So I don't know what the reimbursement/regulatory issues are right now in terms of considering this outside a trial setting. Maybe it’s going to end up getting an indication. But at least right now at this moment, is this what you would prefer to do with your up-front treatment of follicular lymphoma? DR FLOWERS: The landscape in follicular lymphoma is becoming increasingly complex, in part because of the number of newly approved agents in this setting. I think we’ve got a number of new oral agents that are being explored in follicular lymphoma: ibrutinib, lenalidomide and potentially chemotherapy-free approaches to patients with follicular lymphoma, both in the front line and in the relapsed setting. If this gets FDA approved in this setting and the publication shows sustained benefits for this population, particularly if there ultimately is shown to be an overall survival benefit for patients who get obinutuzumab plus chemotherapy that this is a regimen that will be considered as one of the new front-line standard of care approaches for these patients. As of yet, while this is an approved regimen, I would wait to see the ultimate publication from these results and see how sustained those benefits are in terms of overall survival benefits. DR LOVE: So it sounds like you’re not jumping up and down, ready to start to do this. What’s your thinking? DR FLOWERS: I think that our chemotherapy still is with maintenance, based on the PRIMA results, still is a standard approach for patients with follicular lymphoma that has meaningful benefits. Obinutuzumab is approved in combination in the relapsed setting for patients with follicular lymphoma. And so it can be used in that setting as well. And there are a number of other agents that can be used in the relapsed setting. I think when you think about particularly older patients with follicular lymphoma, you need to think about not just what will you give as the best first-line therapy but what options are there for sequences of therapy over the long run. I think this is an approach that, with the 2 years of maintenance, can potentially provide progression-free survival benefits where people can receive this as their front-line therapy and go for a long time without subsequent therapy. But it really amounts to what strategy do you want to take for a patient with follicular lymphoma? Do you want to use your best regimen up front and hope that they don’t need therapy for a very prolonged period of time or use a regimen that provides meaningful benefit, knowing that you have a number of options later on? DR LOVE: Right now, how are you incorporating obinutuzumab into the management of FL? What’s the typical situation where you might use it? DR FLOWERS: Yes. Obinutuzumab currently is something that I use in FL predominantly in clinical trials in the relapsed setting, where we have a number of clinical trials that are using that agent. Occasionally for patients in the relapsed setting when they’ve had multiple lines of therapy, it’s something that I will look at in combination with bendamustine for patients who have either not received prior bendamustine or have had a long treatment-free interval between when they received bendamustine and the current treatment that you’re considering. But, there are so many agents in the landscape of follicular lymphoma, it’s one that I’d like to see a little bit more data on before moving it directly into the front line. But I think it will be a meaningful therapeutic options for a number of patients and one that other clinicians can choose as a front-line approach. |