EMN 2021 | Maintenance therapy in young patients with myeloma

So, my talk at EMN 2021 was around maintenance strategies in younger patients with multiple myeloma. I first talked about the data supporting the use of Revlimid, or lenalidomide, maintenance after a stem cell transplant.

There is now a convincing body of evidence that lenalidomide maintenance can not only prolong progression-free survival by a significant amount, on average around 20 to 24 months, but also can prolong overall survival. We have a depth of data from the IFN, the CALGB study and Professor McCarthy’s meta-analysis. We also have the data from the Myeloma XI study. And if you put all of these together, there really is a strong hazard ratio in support of Revlimid maintenance, not only for progression-free survival, but also for overall survival.

I also highlighted that Revlimid maintenance can be proven to be effective from community or real-world data, and I highlighted the data from the Connect database that was done in the United States looking at maintenance with Revlimid versus no maintenance. And this Connect database presented by Sundar Jagannath and it was in Blood Reviews, showed that you can see the same progression-free survival advantage and the same overall survival advantage, even in the real-world setting. And there are now a number of studies in the real-world setting confirming the efficacy of Revlimid maintenance.

I think there are now a number of questions, however. Does Revlimid maintenance suit all patients? Certainly I could, I can present data and have presented data to suggest that patients, whether they’re MRD negative or MRD positive, benefit from Revlimid maintenance, and patients who are high-risk or standard risk such genetics benefit from Revlimid maintenance.

I think however, there are a number of open questions, particularly around high-risk cytogenetics. There is no doubt that patients with high-risk cytogenetics do do better on Revlimid maintenance than patients who have high-risk cytogenetics without maintenance, but they don’t do as well as standard-risk patients. So, it may well be that we need to think further about patients with high-risk cytogenetics for a maintenance strategy beyond Revlimid alone.

I think also there are a number of really exciting studies coming up. First of all, there is a maintenance question in the FORTE study from Francesca Gay, and this shows that the addition of carfilzomib to Revlimid was associated with an improvement in progression-free survival across all risk groups. We know of course that, from the HOVON data, that Velcade maintenance after PAD induction and stem cell transplant is particularly important in patients with 17p deletion, and I highlighted this data. We’ve also seen data from ixazomib maintenance studies showing that ixazomib given for two years after stem cell transplant can be associated with progression-free survival advantage of about five to six months.

There are a number of other studies now looking at different maintenance strategies, we have for instance, that Cassiopeia study, which is looking at a dara maintenance strategy. We have the GRIFFIN study, which is looking at daratumumab-Revlimid strategy. And we have an EMN study looking at ixazomib-dara potential combination in the maintenance space. And we have the PERSEUS trial and the AURIGA trial looking at other maintenance strategies going forward.

For me, however, the main questions now are, who benefits most from maintenance? What do we do with patients with high-risk cytogenetics? If patients have prolonged MRD-negativity, can their maintenance be stopped? If we need to use more than one agent, what is the best partner for Revlimid maintenance? And also, as with all maintenance strategies, we have to balance efficacy against toxicity and side effects, particularly in the first remission, when patients have the best possible quality of life. There also is an open-ended question about duration of maintenance, and again, there are a number of studies looking at fixed duration of maintenance versus maintenance until disease progression. We also have to be mindful that any maintenance we might give may have an impact on disease biology, and this is something we need to be watchful of.