Dr Joseph Mikhael – International Myeloma Foundation
Prof James Chim – Queen Mary Hospital, Hong Kong
Prof Evangelos Terpos – University of Athens School of Medicine, Athens, Greece

JM: Hello and welcome. My name is Dr Joseph Mikhael, I’m a Professor at the City of Hope Cancer Center and the Chief Medical Officer of the International Myeloma Foundation. It’s a pleasure to chair this session with you today hosted by ecancer on patient treatment preferences in relapsed and refractory multiple myeloma. I’m very happy to have two of my friends and colleagues joining with me today who I will allow to introduce themselves.

JC: Hello everybody, I’m Professor James Chim from the Queen Mary Hospital, University of Hong Kong.

ET: And I am Professor Evangelos Terpos from the University of Athens School of Medicine in Athens, Greece.

JM: So we’re going to be talking today a lot about the really changing dynamic of relapsed multiple myeloma but specifically how it affects the conversations we have with our patients. Thankfully we’re in a day where we have so many more options than we used to have. The three of us have been around long enough to know, sadly, the days where we maybe had one or two options in relapsed myeloma, so you didn’t really have a lot of choice for your patient. But now, thankfully, we have multiple choices, choices that are all oral regimens, others that are intravenous, subcutaneous, some are daily, some are weekly. We know here, at the American Society of Hematology annual meeting in San Diego, there has been a lot of discussion about what patients prefer. I’m really quite intrigued by some of the research that’s been presented to help us understand and inform that conversation we have with patients. Professor Terpos, let me start with you. When you think just in general about patient-centred care, what does that look like for you in the clinic that you have in Greece?

ET: First of all, I think that the most important thing is that the patient has to be very well informed. There are so many agents that we have, so many regimens that are available, not in many countries, let’s say, but in countries like Greece that we have almost everything that is approved in Europe by the EMA. So the patient has to be very well informed for the efficacy and the safety of each one of the regimens in order to decide. Of course, the condition of the disease for each patient because for the myeloma we believe that almost every patient has his own disease, so I believe that it is crucial in order to let him or her know the best information for the best regimen. So it’s not only what we believe that is best for our patients but also we have to discuss what the patient needs because the patient may work, may want to be in their everyday life, everyday being at work, because it’s crucial for him to be good with the family, to have family support. It’s another thing if the patient is elderly and frail, if the patient is young and fit. So we need to give him the best information and to have a decision with him what is the best option for the treatment. Let’s give you an example, if I may. We have a young patient with an aggressive disease, on the other hand, the patient wants to be at work every day, for example, so we need to give him the best information of the treatment options that he has and to persuade him that possibly, at least for some period of time, one or two months it’s not so possible to be every day at work because it is more important to control the disease. But then when we manage to have that, possibly after autologous transplant when we have a maintenance phase, then we can have the best for him in order to be at work, to have an ordinary life and be back again.

JM: So, Professor Chim, how do you match that? All the options that we have with the patient preferences, how do you connect those dots together with the patient? What kind of discussion do you have with them to help you choose that best therapy with the patient involved?

JC: I have to first of all echo with you that actually we are in an era of blessing that we have so many agents that are available for the treatment of this very difficult disease of myeloma these days as compared to about ten years ago when we had only, say, conventional chemotherapy that had a very low response rate and a poor survival. Now we have very effective agents that actually prolong survival so much. But at the same time I believe that even for us as a clinician we actually are at the time of a challenge because we have so many drugs. Actually there are so many clinical trial data that keeps coming up, maybe every month of the year. So as a clinician first of all we have to be very updated about actually the most advanced clinical data that’s available. We have to integrate that piece of data to the clinical order of them for our patients in order to give so-called the best treatment for our patient at the soonest stage of disease. But at the same time for the patient, I can’t agree more with Evangelos that the patient, every patient is an individual and their disease is entirely different. Although they may have a myeloma, some may have very symptomatic disease and some have more indolent disease. So actually the requirement for them actually might be different and also the age of the patient might differ. So I believe that the aim, the goal of the patient, may be quite different indeed. For example, I’ll quote you an example in Hong Kong, for example. If the patient has to attend a hospital visit, either for a follow-up or for administration of drugs, usually, very often, they are actually escorted by another family member. For the elderly patient they are accompanied by a young member of the family and even for a young patient, because they feel more comfortable if they are being escorted by another family member. So in most of the cases we understand that the cost of the treatment is actually accounted for but actually the cost of this additional family member escort is not accounted for and actually it’s missing in the equation. And also because of that the number of hospital visits really matters. So I believe that in the case, as Evangelos mentioned, there are so many protocols, so many regimens now and some of them, as Evangelos pointed out, may have comparable efficacy. In that connection I believe that we have to inform a patient clearly about the different adverse events, inherent individual protocol and also maybe about the number of hospital visits or the convenience, so-called, that will incur to the patient.

JM: I think that’s so important. When I look back over cancer care evolution in the last twenty years one of the things we learned was doctors think one way, nurses think one way and very often patients think a third way. We have now evidence presented at this meeting that helps inform us a little bit more. I fully agree with both of you, thankfully we have choice now, we have to incorporate side effect profiles and the convenience of regimens in our discussions with the patients. We can’t just walk in and say, ‘This is the progression free survival, it’s two months longer than this regimen, so let’s go with regimen number one.’ But this data that’s presented here at ASH this year is helping to inform some of that for us which is really important. I don’t want to be so arrogant to think that I know what’s best for my patient. Several abstracts are presented here at ASH and I’ll just summarise one or two of them but some major themes came out to me from this work that was presented, some of it I happened to be a privilege of being a part of and some of them were done in different countries. So we have a really nice sampling in different places. Three key themes that came out to me: theme number one, there is really a difference among patients. It wasn’t like everybody answered the same way. So when they were given, whether it be scales or preferences – would I rather have more visits with a longer progression free survival or fewer visits with a shorter progression free survival – there wasn’t an absolute unanimity. So one of the take-home lessons today is clearly not every patient thinks the same way. Both of you have brought that out in your conversation.
The second thing was absolutely survival is important, overall survival is most important to patients earlier on in their disease course, but with each subsequent treatment of course overall survival is always more important but there is a greater emphasis on quality of life. So as we’re treating patients with more and more regimens we need to be more sensitive to the side effects that they are experiencing. In a disease that we haven’t cured we know that it’s really important that the quality of life be preserved. Then maybe the third theme that I found interesting was that there were certain side effects that they were particularly cognisant of, of which perhaps the most important was nerve damage. I think it’s probably because it can often be irreversible, once a patient has neuropathy it’s not reversible. What do you think about those themes, the themes of not all patients think the same way, of course, survival is always important but has a bit of a decline in its importance over subsequent therapies and the importance of side effects, specifically of neuropathy? Perhaps back to you Dr Terpos, what do you think about that?
ET: I totally agree that the different types of patients, not only based on the age but also on the psychology of the patient, think differently. I believe that the more young patients have greater ideas about overall survival – it is important for them, they have families. Someone who is 40, 50 years of age so they care a lot about their children and they want to have a lot of years, if possible, in order to make them grow and become members of society. For the younger patients they can tolerate more aggressive therapies in order to survive more. But if someone is 80 years of age of course he’s much interested in having more years but, on the other hand, many of these patients tell me, ‘Doctor, I know I am 80 years of age, I am near the end of my life. I don’t want to suffer with giving me treatments that may make me be in a chair or if I cannot do my everyday life.’
JM: Some of that suffering, as I understand it, is the symptoms, but also the frequent visits. Like you were mentioning to us that, I hadn’t really thought of it that way, that you’ve got to account for the person who is being treated but the driver and sometimes the person that’s accompanying them. That really multiplies visits; in fact that was one of the sub-themes of the research that was presented was that patients do have a concern about how frequently they come in to the clinic. Have you seen that as well in your patients?
ET: Of course. A 75, a 72 years of age old lady without a husband or, let’s say, wants a member of the family, maybe the daughter or the son, to accompany her in the hospital. So the person has to be out of work and many times the patient worries about this absence of the daughter or the son of the work. Because many times if this continually happens they may lose their job, let’s say, in some countries, for example, and they are worried a lot. So they prefer to come less often in the hospital even if their treatment regimen is not the best regarding efficacy. But on the other hand also safety is important, mainly for the elderly, for all of them but mainly for the elderly. We come from the era of thalidomide initially and bortezomib afterwards, both drugs have as a main side effect the neurotoxicity and I can tell you that the patients cannot tolerate the neurotoxicity, it’s a great issue for them and they prefer more and more regimens that don’t create that adverse event which is very dramatic for their quality of life.
JM: Has that been your experience too, that neuropathy has really been something that… I think of the early days where maybe we as healthcare providers didn’t quite pay as much attention to it when you didn’t have many choices. But do you find your patients talking to you more about neuropathy? Do you find that you’re more sensitive to it when you discuss it with them in the clinic?
JC: Oh definitely. Because in Hong Kong we still use induction, usually in the way of Velcade thalidomide induction, even so. So that’s why we go for Velcade, as Evangelos pointed out. Both bortezomib and thalidomide give rise to neuropathy and, of course, in that connection we are seeing patients more and more complaining about neuropathy. I believe that that actually matters in both young patients and also elderly patients. You can imagine for the elderly patients if they have a painful neuropathy that actually wakes them up in the middle of the night it’s really disturbing and actually they have a very poor quality of life. They’re at that age, I believe, that quality of life is important. Of course survival is always important but to some patients quality of life, especially in the way of neuropathy, is certainly quite… it makes them very uncomfortable.
JM: And with some of these choices that we have that has influenced the way we’ve given some of these regimens. I practice here in the United States, of course, we tend to use a lot less thalidomide although sometimes we still may employ it. But even in our use of bortezomib, being able to be so sensitive. I always say as soon as the patient has that hint of neuropathy then we have to make a change, usually with a dose reduction or perhaps even a dose frequency change to every other week. Now that we have these other choices, be it ixazomib or other proteasome inhibitors, we’ve been able to make that move. That’s critical too and if the communication with the patient is open and honest and clear it facilitates that. In fact, I would suggest that perhaps one of the most important abstracts that I’ve seen recently published, it was actually a plenary abstract at ASCO, was this analysis, it was a randomised trial, of providing to patients a better avenue to communicate with their physician team, through an iPad actually, compared to the standard of care which I suspect in most of your clinics and mine, they call, they leave a message, the nurse calls back and it’s not a bad system but that is the standard of care. They designed the study with a lot of quality of life metrics to demonstrate that enhanced communication between the physician team and the patient would improve their quality of life. The surprise, a beautiful surprise, was it not only improved their quality of life but actually their quantity of life. So I like to say now we have these great agents that prolong survival and we want them but you can prolong survival by having the right conversation with your patient, by discussing with them. That’s why I’m excited to know that even here at ASH these patient preferences abstracts have been profiled at a high level, many of them have been oral abstracts in that. And I know as our time wraps up here, does that resonate with the two of you? Do you find that that communication with your patient really can influence their outcome in the long term?
ET: First of all it is extremely important because the well-informed patient is a patient that can have the right decision for the disease. Also when the patient has the first symptom, as you mentioned, mainly for peripheral neuropathy, can communicate directly with the doctor and tell him, ‘Doctor, I have this [?? 16:40] in my hands and I have this problem.’ Then the doctor immediately may take action in order to reduce, as you may, to reduce the dose, to increase the interval between the two doses in order not to have this side effect.
JM: And if the patient was inhibited to have that conversation it might be much later, by the time the neuropathy becomes painful, that they’re interacting with their treating physician.
ET: Of course and sometimes the neuropathy becomes painful very rapidly, so before coming to the next visit to the clinic and seeing the doctor or the nurse. So, as you mentioned, in the very nice study that was presented at ASCO, if the patient can communicate on the same day and say to their…
JM: ‘I have an impact…’
ET: Yes, ‘I have an impact,’ because you can reduce the dose immediately or you may schedule an unscheduled visit in order to see him and discuss in more detail what’s happening in order to…
JM: And has that been resonant with you as well?
JC: Definitely. I think that this is very important, that doctor-patient communication is very important. I believe that these days, because I understand that there are a lot of medical doctors are trained scientifically, they have a scientific mind, so they treat the myeloma as a disease. But I believe that we agree that we really have to treat the patient as an individual, as a human being. So I believe that it’s not just about when we treat the disease obviously we have to be scientific about the drugs, efficacy etc., about adverse events, and we have to integrate these things together with the patient’s preference, that’s very important. At the end of the day we don’t want to render the patient a longer survival but with a painful life. I believe that, so that’s why I believe the doctor-patient communication is very, very important.
JM: Absolutely. Well it sounds like we all agree on this and although it may sound simple, as I try teaching my residents and fellows, we don’t treat myeloma, we treat people. I think that we’re going to see more of these patient preference like studies being done and influencing the field. Thank you very much for joining us today for this discussion on patient preferences in relapsed refractory multiple myeloma with ecancer. We trust it’s been a help to you in the care for your patients. As we’ve said many times today, that communication with the patient genuinely influences their quality and quantity of life and we trust this will be of help to you. Thank you again for joining us.
ET: Thank you.
JC: Thank you.