Younes Discusses Key ASH Data in MCL, DLBCL

Anas Younes, MD

The fields of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) had a handful of updates presented during the 2016 ASH Annual Meeting. While some had the potential to be more practice changing than others, says Anas Younes, MD, all of these latest findings educate the community on existing and explorative treatment options for patients.

In MCL, for example, results of a randomized trial demonstrated that the addition of rituximab (Rituxan) maintenance therapy after stem cell transplantation for younger patients led to an improvement in survival without disease progression or clinical events.

Patients randomized to rituximab maintenance had an event-free survival at 4 years of 78.9% versus 61.4% in patients who did not get maintenance therapy (P = .0012). The 4-year progression-free survival (PFS) was 82.2% with rituximab maintenance and 64.6% without (P = .0005). Overall survival (OS) at 4 years was 88.7% and 81.4%, respectively, for rituximab maintenance and no maintenance (P = .0413).

OncLive: What did you discuss at this State of the Science Summit?

In an interview during the 2016 OncLive^® State of the Science Summit on Hematologic Malignancies, Younes, chief of the Lymphoma Service at Memorial Sloan Kettering Cancer, discussed updates in DLBCL and MCL that were presented during the 2016 ASH Annual Meeting.Younes: There were a good number of randomized trials reported at the 2016 ASH Annual Meeting this year. In DLBCL, there were 3 randomized phase III trials in untreated patients with DLBCL in unselected patients. Two of these were for all-comers—mainly patients who are 18 and older—and 1 only for older patients.

The first one—EPOCH-R versus R-CHOP, were long-awaited results. So far, it looks negative—meaning that R-CHOP was exactly the same as EPOCH-R. We don’t have a subset analysis based on the cell of origin; that will be reported later on. In a nutshell, EPOCH-R is not superior to R-CHOP in unselected patients. R-CHOP remains the standard of care for the majority of patients with newly diagnosed DLBCL.

The second one was a comparative trial between 2 anti-CD20 antibodies: R-CHOP versus G-CHOP, where the “G” is obinutuzumab (Gazyva). Again, this was done in unselected patients in a large randomized trial. There was really no difference in outcomes in terms of PFS or OS. Therefore, G-CHOP is not going to replace R-CHOP; R-CHOP remains the preferred CD20-based antibody that is combined with R-CHOP.

The third trial, which is interesting, looked at a different question. What happens if we give maintenance therapy with lenalidomide (Revlimid) for 2 years after R-CHOP versus placebo, but mainly in elderly patients aged 60 to 80? There was an advantage for giving lenalidomide in a maintenance setting in terms of PFS, but there was no difference in OS. These are positive data because the primary endpoint was PFS, but because you expect PFS to translate into an OS benefit, it was not [all positive]. For practical purposes, I don’t think this will change the standard of care either. It could be an option if it gets approved, but I don’t know if it will be approved by regulatory agencies for that indication, but it’s an interesting trial.

There were also late-breaking abstracts regarding the KTE-C19 CAR T-cell therapy, which are very impressive data. This was a good number of patients—more than 70—and they were all refractory DLBCL with primary mediastinal and transformed follicular lymphoma. There was an overall response rate of about 70% with a high complete response rate. We don’t know about the duration of response or PFS because the follow-up remains short, but it’s a very unexpected high response rate in this very difficult-to-treat patient population.

For the 2 studies that seemed to show that R-CHOP remains the standard, what does this mean for the role of R-CHOP going forward? Is it still worth it to investigate similar regimens against it?

In MCL, there were a few phase I/II trials with a small number of patients; however, 1 randomized trial may change the standard of care. This compared the outcome of patients who received autologous transplant, with young patients with induction therapy with R-DHAP followed by beam-based autologous transplant. Then, they were randomized to receive either rituximab maintenance for 3 years or observation. Those who received rituximab maintenance did better with PFS, event-free survival, and OS. This will change the standard of care for patients who are receiving autologous transplant. It would be reasonable to give them rituximab maintenance in this group of patients.R-CHOP remains the standard of care, and it’s interesting because, if you look at these randomized trials where R-CHOP is the control arm, the control arm continues to perform better than what initial trials reported. It’s difficult to change this regimen even though it’s an old regimen. The strategy will continue to be the same. R-CHOP plus drug X versus R-CHOP, or R-CHOP followed by drug X versus R-CHOP, or maybe the combination of R-CHOP plus drug X followed by drug X as maintenance. These strategies continue to evolve.

What are the next steps with CAR T-cell therapies in this space?

You chaired this evening’s State of the Science Summit. What is the value in having an event like this?

There are 2 randomized trials for which we are still waiting on the results. This is for patients with the GCB or ABC subtype, comparing R-CHOP plus ibrutinib (Imbruvica) versus R-CHOP. This completed enrollment and should report results in 1 year and a half or so. The other is R-CHOP plus lenalidomide—so it is concurrent administration, not maintenance—versus R-CHOP alone. We will see what will come out of this trial.The results are very impressive. It will be important to follow up with these patients and see what the PFS is and how many patients, if any, will be cured. It depends on these results, and then the whole field may change. If you have the patients who respond remain in remission for 2 to 3 years, it will be amazing because these patients potentially have no other curable options. Some of them have received 6, 7, or 8 prior regimens. To find a therapy that works for these patients and potentially put them in long-term remission is unprecedented, but the data are not there yet, so we will have to wait.Even though I have tried my best to sit through as many ASH sessions as possible, no one can do that. It was educational to listen to my colleagues giving talks about their areas of interest and expertise. I’m sure that, for the people who did not attend ASH this year, they had an even greater benefit.