DR SCHIFFER: There were 2 abstracts in which patients in response were randomized to receive rituximab maintenance or ofatumumab maintenance. And in both studies, the predictable thing happened. That is, if you continued therapy — in this case with antibodies — the progression-free survival was prolonged. But it appears that the overall survival is not prolonged. We’ve seen this in myeloma. We’ve seen this in follicular lymphoma. And the issue it comes down to, is progression-free survival a surrogate for clinical benefit? There are toxicities and costs associated with maintenance therapy. Not too many in this case, but there are some. And the other question is whether you’ve used up your therapy for relapsed patients. That is, if you maintain them with the antibody, will that make it so they can’t be used when their disease inevitably progresses?

There has, I think, become less enthusiasm for rituximab maintenance in the follicular lymphomas for that reason. And I would defer to Jennifer for her thoughts about it, but I don’t think it’s anything that should approach standard of care, based on these 2 abstracts.

DR LOVE: So yes. I would be curious on your thoughts about this, Jennifer, because we poll everybody all the time, investigators, docs in practice. And we have heard investigators say, “I’m changing what I’m doing about CLL maintenance.” Charlie said this was kind of predictable, but what have we known prior to these 2 presentations about maintenance, and what did you think about these 2 data sets?

DR BROWN: Right. Prior to this, no one believed that there was a benefit for rituximab maintenance in CLL. There weren’t any randomized data. But the relatively limited Phase II data didn’t suggest a marked improvement in quality of response over the course of rituximab, and there was some significant toxicity in terms of both infections and cytopenias. And we also know rituximab as a single agent is really not a great drug for CLL, which makes one think, a priori, that it may not work that well at clearing minimal residual disease. And so even though this is a common outcome, that progression-free survival is improved without overall survival, I was mildly surprised at the results. But I don’t find it practice changing either.

I think there are a number of concerns about it, that the toxicities in CLL patients compared to even follicular lymphoma are likely greater because of greater preexisting cytopenias and greater infectious risks. The fact that there is no overall survival benefit, the fact that we have a number of other agents that we’re studying that are potentially more interesting I would suggest, as maintenance in the setting of BCR pathway inhibition, continuing, although that becomes a very important question that we can add to the long list of questions that we don’t understand about CLL.

If you continue a BCR pathway inhibitor indefinitely, when people relapse they will certainly be resistant. And we don’t know if being resistant to one confers cross resistance to another. Maybe it would be better to do a defined period of therapy, give people a treatment break that might last for a long time, and then be able to potentially re-treat on relapse.

DR LOVE: I guess we should point out that the rituximab maintenance study was done in first and second line and the ofatumumab study, I believe, was done in second
and third line. But in terms of the magnitude of the benefit, if a patient were to ask you or a fellow were to ask you in general how much additional progression-free survival do you think it would provide, how would you answer?

DR BROWN: So I was more impressed by the ofatumumab results in that regard, but they’re a little bit harder to interpret, because most of the patients probably had rituximab-containing chemoimmunotherapy. That actually was not reported in the presentation but was likely. So they’re actually adding a new agent. And that did increase the median progression-free survival. It approximately doubled it, from 15 to 30 months, but it’s adding a new agent, essentially, which is how I would probably counsel the patients. It’s also not so relevant now because we’re going to be using less and less chemoimmunotherapy in the second- and third-line setting.

DR KANTARJIAN: Jennifer, I find a prolongation of 15 months of disease-free status fascinating because, as you said, these drugs on their own do not have much efficacy. But if you give them in this situation, they can give you 15 months without disease.

DR SCHIFFER: No.

DR BROWN: Ofatumumab, not rituximab.

DR KANTARJIAN: Right.

DR SCHIFFER: No, no. Progression-free survival.

DR KANTARJIAN: Right.

DR SCHIFFER: Not disease-free survival.

DR BROWN: Right. And most of the patients were certainly partial remissions.

DR SCHIFFER: Right.

DR BROWN: In a second- or third-line setting.

DR KANTARJIAN: But then that opens the possibility, if that’s so effective, can we do combinations with the B-cell receptor inhibitor and the monoclonal or lenalidomide and the monoclonal or checkpoint inhibitor and the monoclonal? I think it’s fascinating that those progression-free survivals were in the order of more than a year. That really opens our eyes —

DR BROWN: Ofatumumab, it was.

DR KANTARJIAN: — to the possibility that you can change the natural history of the disease completely.

Chronic Lymphocytic Leukemia (CLL)

Chronic Myeloid Leukemia (CML)

Acute Myeloid Leukemia (AML) and Acute Promyelocytic Leukemia (APL)

Myelodysplastic Syndromes (MDS)

Acute Lymphocytic Leukemia (ALL)