CC-486 Maintenance Therapy in AML

Harry Paul Erba, MD, PhD: Gail, you’re going to lead the last section before we get to concluding remarks. I would like to preface this, maybe controversially, by saying maybe this is the next practice-changing thing that’s coming for AML [acute myeloid leukemia]. Tell us about CC-486, also known as oral AZA [azacitidine].

Gail J. Roboz, MD: I don’t think it’s controversial. I’m going to just go out there and say that this is going to be practice changing in AML because I’ve been working for so long that it has to be practice changing in AML, otherwise it will be too depressing. But we had some very gratifying data that were released at ASH [the American Society of Hematology Annual Meeting], and then we had some follow-up data that were presented at the EHA [European Hematology Association Congress] looking at CC-486 in the QUAZAR study. This is an oral formulation of azacitidine. I want to say quickly and out there in front that it’s not just the same thing. It’s not going to be a 1:1 easy substitution, and there’s lots of discussion about where CC-486 could potentially be used instead of currently available formulations of AZA [azacitidine]. But that’s not what this study was.

What this study looked at were patients who were treated with intensive induction chemotherapy, older than 55 years old, who were deemed ineligible for stem cell transplant. Patients were in remission. Patients were in remission, CR [complete response] or CRi [incomplete count recovery], and then they were randomized to CC-486 versus placebo. It’s a clean study, hundreds of patients, international, placebo controlled, all the good stuff. Basically there was a very clear overall survival benefit for the patients treated with CC-486.

Some of the additional data, which were really gratifying, showed, first of all, the patients were in pretty good shape in terms of health-related quality of life when they started the study. They were reporting solid measures of quality of life in remission. For the ongoing therapy, we’re talking 12 cycles of therapy. A lot of these patients were on it for a long time. I actually have the longest patient on it in the United States. I think we’re at 7 years at this point.

These patients were able to maintain their very good quality of life, so this was feasible to administer. It was also feasible and tolerable in older patients, in patients more than 75 years old. For those patients, yes, you can do transplant, but it’s a struggle. A lot of patients over 75 years old don’t want to do a transplant even if they can do it.

Maintenance has not shown an overall survival benefit to date in AML. This is a first. It’s with a tolerable agent. I think it’s going to change practice. It’s going to be stressful initially to figure out who should get this. If the question is, should I not do a transplant, should I get this instead, this study didn’t answer that question. This wasn’t a head-to-head study that do you do maintenance or do you do transplant. But we’re digging very hard into the data to try to answer as many questions as possible about which patients will benefit from maintenance. In combination with other studies that have suggested a maintenance benefit for hypomethylating agents [HMAs], this is suggestive that ongoing treatment with an HMA might be a good thing. After regular chemotherapy, it might be a good thing to have ongoing cycles, for example, of HMA–VEN [venetoclax]. Will you be able to substitute CC-486? I’m not sure.

Of course the post-transplant azacitidine is another interesting area to investigate, since there have been some data suggesting restoration of chimerism and staving off relapse by using azacitidine post-transplant. I find these very encouraging data, very thought provoking, and I can easily envision another decade of study to figure out what we can actually do here.

Transcript Edited for Clarity