Expert Touts Value of Lenalidomide Maintenance in Myeloma

Graham Jackson, MD

Lenalidomide (Revlimid) as a maintenance treatment for patients with newly diagnosed symptomatic multiple myeloma demonstrated encouraging phase III findings in the Myeloma X1 trial, which were presented at the 2016 ASH Annual Meeting.

In the multicenter, open-label, randomized, UK study, 1550 patients were randomized to receive maintenance lenalidomide or observation following maximum response or at 100 days after transplant.

Results showed that the lenalidomide maintenance therapy arm was associated with a 55% reduction in the risk of progression or death compared with the no maintenance arm (HR, 0.45; 95% CI, 0.39-0.52; P <.0001). The median progression-free survival (PFS) was 37 versus 19 months for lenalidomide maintenance and no maintenance, respectively.

OncLive: Can you provide some background on this maintenance study?

What were the primary results?

In an interview with OncLive during the meeting, lead study author Graham Jackson, MD, professor, consultant hematologist, Newcastle Hospital, provides an overview of the study and the impact of maintenance therapy with lenalidomide on the landscape of multiple myeloma.Jackson: The Myeloma XI trial that we presented is a large phase III study conducted in over 100 centers in the UK. We recruited more than 4000 patients to the trial in its entirety. The data being presented are about lenalidomide maintenance, and examining patients who went through their treatment and responded. They were randomized on a 1:1 basis between lenalidomide maintenance and no maintenance treatment.The findings of this study, in about 850 patients, is that lenalidomide—throughout all patient populations—increased the number of people staying in remission. The PFS across the whole cohort increased by about 22 months and, for the transplant-eligible patients, by nearly 28 months.

What is the main takeaway from this study?

Even for the older population, the PFS increased by over 12 months. All patients, of all ages, benefited from the lenalidomide maintenance. The results really confirm the data that have been put together looking at the meta-analysis of lenalidomide maintenance. Our results really nicely integrate with this, showing that lenalidomide maintenance is now the standard of care for patients with myeloma in their first response.There is now a huge body of evidence across a large number of patients. There were 857 patients in our study who went on to receive lenalidomide maintenance. We have shown that it is safe, deliverable, and really prolongs remissions. It prolongs the remission of patients who are in a transplant-eligible group. It also prolongs the remission in those patients who are older, frailer, and are not eligible for transplant. It's an across-the-board benefit.

How was the adverse-event profile in this study?

We have shown it’s safe. There were some questions about the instance of secondary malignancies in this group of patients, but we have also shown that this incidence of second primary malignancies is really not as significant as we first thought.Some main adverse events from lenalidomide maintenance are around hematological toxicity. The most common grade 3/4 toxicity was neutropenia. We didn't see a lot of infection and, on the whole, most patients seemed to tolerate the treatment very well. Of course, with lenalidomide maintenance, you can adjust the dose so the patient stays on the therapy without having to come off the drug because of toxicity.

What are the next steps of the study?

Is there anything else that was presented at the 2016 ASH Annual Meeting that you found exciting?

What are some of the challenges in myeloma that you would like to see addressed in the next few years?

One of the interesting pieces of data we are looking at shows that, if patients stay on maintenance longer, they benefit more. We saw that patients who came off the study early because of toxicity generally relapsed quicker than patients who managed to stay on the drug. Obviously, there are a number of reasons why that might be; however, it does speak to the possibility that prolonged maintenance is important.The next steps are that are we are going to look at overall survival (OS). The meta-analysis would suggest that patients who are on lenalidomide maintenance gain an advantage not only in PFS but also in OS. The data suggest that it might be as long as 2 years. We should have a readout on that data very soon. Hopefully, we can confirm that, not only is there a PFS advantage from lenalidomide maintenance across a large group of patients in the study, but there is a survival advantage, too.This has been a really exciting meeting, in terms of the myeloma data. The daratumumab (Darzalex) combinations continue to be exciting. We've seen the POLLUX data presented by Philippe Moreau, MD. Those data look really stunning. The researchers looked at minimal residual disease in those populations and showed that they can achieve some really deep responses. It looked like they were doing really well. That's exciting.There are many challenges we still face in multiple myeloma. The number one challenge is the fact that we are still not curing all the patients. We do very well with patients who respond and have low-risk disease. Clearly, there is a lot of focus on patients with the highest-risk disease—the patients who go through their treatments very quickly and only respond transiently. With that group, there is a clearer unmet need, even now.

Also, patients become refractory to a number of different therapies. We've seen a very nice piece of data called the STORM study about selinexor (KPT-330) in that group of patients. That study looks interesting. There are more novel agents coming, which is exciting.

Jackson GH, Davies FE, Pawlyn C, et al. Lenalidomide is a highly effective maintenance therapy in myeloma patients of all ages; results of the phase III Myeloma XI study. Presented at: 2016 ASH Annual Meeting; December 3-6, 2016; San Diego, CA. Abstract 1143.