EK: Hello, we are in EHA 23, we are at the ecancer event. My name is Efstathios Kastritis, I’m a haematologist from Athens, Greece, together with my colleague:
ZF: Zhengzheng Fu, I’m a Chinese doctor. So nice to meet you.
EK: So we will discuss about the current situation in multiple myeloma and also the very interesting results of the INSIGHT study. So multiple myeloma today, more or less, we can say that the treatment of the disease is based on basically two decisions. One is whether we’re going to transplant the patient or not and the other is for how long we are going to treat the patient. So for the patients that we intend to proceed to autologous transplantation we start with an induction regimen, usually based on bortezomib, but this is not always the same across the globe. Then this is followed by autologous transplantation and then, in some countries where approval for maintenance exists, physicians also prescribe maintenance, usually with lenalidomide. Then there are the patients that are not eligible for transplant, these patients are treated with induction regimens, usually for a fixed duration of time. Bortezomib is widely used in these patients but in the last two or three years we have the approval of lenalidomide in first line. In some countries where it is reimbursed, many physicians use lenalidomide at first line. So we now have the data from the INSIGHT study which is a very interesting study, in my view. What do you think?
ZF: From 2000 there are so many improvements in the treatment of multiple myeloma but we are always learning many, many results from the clinical trials but we never know the true word, what’s the good treatment for the patients. So this is the first trial that has records of different countries from Europe, the United States and Asia and the Latin Americas for first line and second line treatment in clinical practice. So it’s very important.
EK: Also it’s very important that this is a prospective study, it’s not an intervention. It’s a non-interventional study so there is a real recording of the real world situation. Because what we have today and we propose to our patients and we propose in the meetings are data based on clinical trials where the patients are very, very selected.
ZF: I know how to treat the patients in China but I never know how do you treat patients in Greece.
EK: Yes, there are many differences between the different countries, even among the European Union. The European Union the treatment is not unified across all the different countries and now we learn about the situation and the needs in Asia, in Latin America, North America, Europe. This is very, very important. So far INSIGHT is the largest prospective study of its kind.
ZF: Yes.
EK: It is very important the fact that it is prospective. It is intended to include 4,000 patients and so far 1,000 patients have been included in the study. Data that are presented in EHA 23 are those regarding the initial analysis of the first thousand patients, still the number is very high.
ZF: Yes, it’s half newly diagnosed and half relapsed patients.
EK: Yes, which shows also very interesting results, both for the newly diagnosed patients and for the relapsed patients. The characteristics of the patients are mostly what we expect to see in the real world population so, for example, the median age of those who are transplant eligible is 63 years, just below the limit that we use in Europe. But for those who are transplant ineligible it’s 67. So, first of all, we see that the age is the age that we see in our clinical practice. So this is the typical myeloma patients. Also it is very important that many of the patients have comorbidities. This is something that is very important because many of these patients perhaps would not be eligible for inclusion in clinical trials because they have comorbidities. For example, 35% of the patients in the analysis so far had Charlson comorbidity index which is 1 or more, so they had at least one significant comorbidity.
ZF: Yes, yes. It’s so interesting that in some the symptoms and the signs because it was said that only 29% of the patients diagnosed unexpectedly during the routine examination. But it’s in China maybe less patients can be diagnosed at a routine blood examination. More patients have symptoms and signs of something like bone pain and renal dysfunction, anaemia, something like that.
EK: This may be also related to the differences for the access to the diagnostic tools in each region. So we have to dissect in a second step how these patients reach their physicians. So maybe the 29% that were diagnosed, not accidentally but before they developed symptoms, how many of them were in Asia, how many of them Latin America, North America or Europe.
ZF: Yes, so we need to wait for the final study, for more patients enrolled in this study.
EK: But still one-third of the patients came to the physician and the diagnosis was made on the basis of bone pain. So this is still a very significant problem. And 6% diagnosed because of kidney failure, this is also very interesting. This is a major problem, we know in our practice it’s a major problem for our patients with myeloma. Another interesting fact is that most of the patients, although they were treated in academic centres, 60% of the patients were treated in academic centres, 85% were not in clinical trials. This is very important. So these are the patients that are not included in the clinical trials. So this is really a real world population, we have real data. What do you think about the management of patients in first line? I mean there are also differences between the different regions in the regimens that they use as induction.
ZF: We are always told that lenalidomide would be the most popular drug but in the choice most people used bortezomib and most people use a three-drug regimen more than two-drug. But by now we don’t know which one is the best regimen but it’s so different from Europe and America.
EK: Perhaps this is because of the differences in availability and reimbursement. In Europe, at least for the patients that are transplant eligible, bortezomib-based regimens, triplets, are used in almost all countries, maybe in 80% of the cases or more. What is different between Europe and the United States is that in Europe we use mostly VCD or VTD while in the United States VRD is more popular.
ZF: So do you think that VRD is the best one?
EK: VRD is a very active regimen, we know there will be no direct comparison between VCD and VTD and VRD. But we have the data from the clinical trials indicating that it’s a very active regimen. But it is important the fact that although we know which are the best regimens that doesn’t mean that all of these regimens can be used in the real world population. You see that also in the second line therapy. For example, it is very interesting that in second line regimens most of the patients are treated with a doublet although we have seven studies showing that a triplet is better than a doublet. But still a doublet is used by most patients. Also what is very interesting is in patients in the relapsed setting is that the majority of the patients are retreated with the initial regimen. So those that receive therapy with bortezomib are retreated, more than 50% of them, with bortezomib again and the same with lenalidomide and thalidomide. So this is very, very interesting, showing that things in the real world are quite different from the protected environment of the clinical trials.
ZF: Yes, the clinical trials people used bortezomib again when they relapsed.
EK: And the other lesson that we learned from this study is that there are many problems and challenges that we have to face in the future. We have the clinical trials showing results comparing very active and very innovative therapies but it seems that there is a long distance between the results of the clinical trials and the real world. Do you think that we will have more patients with triplet in the near future?
ZF: I think so. We must treat patients safer and also more effective.
EK: Safety and effectiveness together, this is something that is a very delicate balance.
ZF: Yes, so we need the more effective and safe drugs.
EK: Also there is the issue of compliance. Many of the triplet regimens are based on parenteral therapies, either IV or sub-cu. So this is not always easy for the patients and the all-oral therapies are not available everywhere. So it’s still an all-oral triplet therapy, it’s not available around the globe. So perhaps in the near future we will see more data on that. Also because of the nature of this study we will be able to have an evaluation of how in time longitudinally we implement the results of the clinical studies and how the clinical practice is changing.
ZF: Maybe we’ll have new drugs, something like the patient can take the tablet so it’s easier for them to have the triplets combined together.
EK: Also the other very interesting aspect of the future therapies for myeloma is the fact that we have the immunotherapies. Now we probably are going to change the backbone of therapy so an immune therapy will become part of the backbone of therapy of myeloma and build on this immunotherapy. But, of course, there are also of challenges with immunotherapy regarding the cost, the availability and also the feasibility of receiving therapy for how long and for how often. So these are challenges that we have to face in the near future but I think, and this is very important, that with this study we will have the opportunity to see where are the gaps and how we can fill the gaps in our everyday practice.
ZF: Yes, so these studies are unique studies.
EK: Yes, and the number of the patients that when all the 4,000 patients are included in the study I think we will have a huge database which is going to be very, very useful to build on further studies and also to design our clinical practices.
ZF: Yes. During this study in our hospital we doctors and the nurses combined together to do this study so it’s very happy for us.
EK: I think that more or less we summarised the results of this interesting study. So we can say goodnight to all our listeners and hope that next year we will have more data from this very important study.