Assessing treatment options for multiple myeloma and managing lenalidomide-refractory disease
Prof Xavier Leleu - Centre Hospitalier Universitaire de Lille, Lille, France
For the talk we give tomorrow, tomorrow Philippe Moreau from Nantes, a colleague of mine from Nantes, was supposed to address two things. Number one is a debate with Josef Mikhael from the US. The US have access to a lot of drugs which, and I’m speaking as a European, is more about most like toys for kids – if you have the money you can buy more toys, if you don’t have enough money you just buy a limited number of toys. But then the question is how you play with your toys smartly altogether. So that’s the US and so the US have this kind of vision that for a number of patients we are very close to being able to say, ‘Okay, you have an ultra-good risk prognostic and you’re going to turn MRD negative, or you have a chance to turn MRD negative and possibly you will never relapse. Or possibly you’ll relapse in 15-17 years and if you are diagnosed at 70 years old, 85, 87, we’ll see.’
What Joseph Mikhael will address in the debate is should we pull all in drugs for cure. So it makes sense for him to address this because, again, he comes from the US where, technically speaking, if you have a good insurance or a lot of money you could really address the question and challenge your physician, saying, ‘Well, I have plenty of money, I’m ultra-rich. Just give me four drugs and cure my myeloma. And can you cure my myeloma with four drugs or can you cure my myeloma with all these emerging new therapies?’ that Hermann Einsele, Professor Hermann Einsele from Würzburg, Germany, will talk about in the end of the afternoon – CAR T-cells, BiTEs etc.
On the other hand, Philippe Moreau, and so I, will debate with Joseph Mikhael on, guess what, there is no point in trying to cure myeloma with an all-in drug approach. Let’s consider that what makes the survival of the patient is not just one line but it’s, in fact, a repeated number of lines of therapy. And 5 plus 5 plus 5 makes 15 years and we are more likely today, in 2019, to take patients to 15 years in three lines than in only one, all-in. So I will be talking about and showing proof that in 2019 it’s a bit of a dream to think that all-in is feasible, all-in is manageable cost-wise, side effect wise, etc., and all-in will take you to 15 years. While it seems to us that it’s more reasonable to accept in 2019 that a number of lines, ideally two or three, I’m not talking about seven or eight, but ideally two or three will take you to 15 years free of death and free of myeloma issues so you could have a reasonable quality of life, a not too costly approach and still living with your cancer in a reasonable state and shape in life. So that’s for the debate in the early morning.
Then there is a round of workshops organised for a smaller group to be able to cover numbers of issues including renal issues and including the type of treatments which is a workshop that Philippe was supposed to cover with actually Joseph Mikhael and I will take over with Joseph Mikhael, a number of workshops on an issue that we start facing worldwide. We’ve learned that a number of drugs we were using in the relapsed setting actually work much better if we use them up front. The best example is, these days, lenalidomide. So lenalidomide is a first in class immunomodulatory drug, Revlimid, and we’ve been using lenalidomide in the relapsed setting for years, since 2005 in the clinical trials and 2008 approved in Europe. But more recently it was approved up front and with great benefit to the patients.
But we’ve also discovered that if the patient relapses while on lenalidomide, so what we call refractory as opposed to exposed but not refractory, the subsequent lines of therapy could be affected by this status. That being naïve or exposed to lenalidomide versus being refractory to lenalidomide is a totally different story when it comes to the next line of therapy. There are a number of data now from clinical trials where patients were recruited either naïve exposed or refractory, showing that the lenalidomide refractory patients tend to do much poorer, even, in a certain extent, similarly to high risk myeloma, almost as if being refractory to lenalidomide up front could be associated to some high risk feature.
So Joseph and I will go through a series of demonstrations that we are at the verge of being able to demonstrate that being exposed to lenalidomide up front is a great thing but becoming lenalidomide refractory may alter the way you treat the patient in relapse. Once we’ve said that then what are the options for the physicians and for the patients and their families? This is where we are in trouble because most of the approved studies that have been leading to drug approval – daratumumab, first in class, only CD38, but also all the proteasome inhibitors, bortezomib, carfilzomib and ixazomib – all these drugs have been approved with Revlimid. But if you are lenalidomide refractory you’re not going to use this combination because it makes no sense. So you need new combinations, non-lenalidomide. So you could propose options to the patients, some of them will be pomalidomide, another immunomodulatory drug from the same family but different mechanism of action, some of them will be non-pomalidomide based. So we’ll cover this tomorrow morning in our workshop.