15th International Myeloma Workshop

Review of data and expert opinion from IMW 2015: Asian perspective

Prof Joy Ho – The University of Sydney, Sydney, Australia
Prof Kiyohiko Hatake – Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
Prof Jian Hou – Shanghai Changzheng University Hospital, Shanghai, China
Prof Sung-Soo Yoon – Seoul National University Cancer Hospital, Seoul, Korea
Prof Je-Jung Lee – Chonnam University Hwasun Hospital, Hwasun, Korea

Joy: Hello. We are here at IMW 2015 in Rome for ecancer.tv. I’m Joy Ho from Sydney, Australia, and I’m joined by my colleagues, Professor Hatake from Japan, Professor Yoon from Korea, Professor Hou from China and Professor Lee from Korea. We’re going to have a discussion about what we’ve learned and what we do at home. So I’d like to start by talking about how we treat transplant eligible patients. I guess two of the most common regimes that we all use are VCD and VTD for transplant eligible patients and then proceed to transplant. I can say in Australia that the majority of transplant eligible patients are transplanted but I gather there’s quite a lot of heterogeneity in different parts of Asia. So I’d very much like to hear what you, in your countries, do and also about your induction regimes. Professor Hatake?

KH: Yes. We do, using a VCD regimen as an induction chemotherapy before the autologous stem cell transplantation for transplantation eligible patients. And after the four cycles we can harvest the prepared stem cells and after that we perform the stem cell transplantation. After that it depends on the clinical research or not but we usually move to the lenalidomide maintenance. This is the first rank. And that’s what we usually do.

Joy: And induction, you use VCD mainly so do you consider the use of a combination of a proteasome inhibitor and an IMiD so for instance substituting cyclophosphamide with an IMiD? Is that possible in Japan?

KH: Other clinical research actually there are regimen too but it’s only in the clinical trial setting.

Joy: Similar in Australia where we are unable to use a proteasome inhibitor and an IMiD together, yes. Perhaps I’ll move to Professor Yoon in Korea.

SY: In Korea so far we have not been able to use Velcade containing agents as an induction chemotherapy for transplant eligible patients. So far therefore we have used thalidomide and dexamethasone as an induction treatment. As of next month, that is the beginning of October, we’ll be able to use Velcade containing agents for transplantation eligible patients in the form of Vel-dex or VCD. So far the mainstay of chemo is thal-dex for transplant eligible patients

Joy: For transplant eligible patients.

SY: Under the age of 65, the age limit for reimbursement by the government funded insurance agency.
Joy: So that’s interesting because, as we heard today, there are groups which are transplanting until the age of 78, in fact, one mentioned. For us, we would transplant up to 72 or 73 depending on biological age. How about Professor Hou in China about the induction and transplant?

JH: Yes, we prefer using VCD for induction and leave the thalidomide for maintenance after transplantation. Yes.

Joy: Combination proteasome inhibitor and IMiD at induction, is that possible?

JH: Some doctors like to combine the bortezomib and thalidomide together in induction, yes.

Joy: And Professor Lee in Korea as well?

JL: Professor Yoon already mentioned the Korean situation. Actually our country can cover insurance from next month so people there our main standard of care is a thalidomide based regimen. Actually I prefer the CTD instead of TD so actually we like to combine the alkylating agent to the thalidomide … we use PCD regimen, that’s a clinical trial, the … group. At the time we have experience to tell the patient in my institute actually I understand that PCD regimen is very well tolerable and a very nice regimen. From next month our country provides some insurance in the regimen of PD and PTD so we were worried to some toxicity of PTD use such as some kind of … yes.

Joy: It is interesting in Japan that you said that you are using lenalidomide maintenance as standard now. It’s certainly not available in our country yet, it’s only used for relapsed refractory. But I guess we can use that to think about the transplant ineligible patients but we hope that according to the data of the first trial we will be able to use len-dex as first line. I wonder, how do you treat your transplant ineligible patients in Japan and Korea and China?

KH: Actually, in Japan how the cases are always associated with lenalidomide maintenance but it depends on the medical insurance coverage.

Joy: OK, so not everyone can get it.

KH: No, not everyone. So we are waiting for the first line chemotherapy using LD, yes. Not yet.
Joy: So in our case, in fact, for transplant ineligible we also very much use VCD as well as bortezomib based rather than MPV according to VISTA but I guess we consider it interchangeable, not that it’s particularly proven. How about in China and Korea for transplant ineligible?

SY: Ineligible patients. Well, because of the government regulation over the age of 65 transplantation is not reimbursed by the government or … insurance reimbursement agency

Joy: So purely on age

SY: Yes, based on age and over the age of 65 therefore we can apply VMP as our first line treatment just like in the VISTA trial.

Joy: But not lenalidomide.

SY: If they progress after a Velcade containing agent then we can apply len-dex, lenalidomide dexamethasone as a second line treatment. So it’s based solely on government regulation, not on a scientific basis.

Joy: Data. Yes, I understand, yes. And in China?

JH: For transplant ineligible patients generally we don’t use melphalan and prednisone because melphalan is unavailable in China, you know. So we generally use VT or TD or VCD or TCD

JL: The Korean situation, we … the regimen in the cycle to treat transplant ineligible patients.
Joy: According to the regulations. I guess along those lines, I have heard, for instance, that the rate of transplantation in transplant eligible patients could be reasonably low. Indeed, we heard even in the US depending on the institution, this morning, that the rates may be as low as 60%. So we’re collecting data in Australia as to what our actual rate is because there are differences between cities and rural areas etc. I wonder, do you have an idea of whether all your transplant eligible patients, the majority are transplanted or some are just treated? Or not just but basically treated like transplant ineligible patients. I guess in Korea, because of the age limit, that is the major issue.

SY: Most of them will be transplanted in the long run.

Joy: Sure. In Japan, in China?

KH: In Japan we don’t have any age limitation but usually we do it when they’re younger than 65 years old. But some institutes do on 70 years old. Yes, so it depends on the institute. But a so-called transplanter would like to transplant.

Joy: Do more. So it does vary between centres.

KH: Yes, even in 70 years old.

JH: In China the percentage to receive autologous stem cell transplantation is about 20%, 25%. The major reason is the … of economic development. I think a lot of older patients could be covered for insurance.
Joy: So do you see that as a big challenge? You probably do want to transplant more patients but are unable to

JH: Maybe the patient is not willing to receive transplantation.

Joy: I see, right.

JH: Yes, because of their cultural background.

Joy: That’s very interesting. So do haematologists try to overcome that resistance to transplantation? I guess it’s difficult.

JH: We are doing our best to educate the patients, namely to receive the transplantations, yes.
Joy: And I guess, moving along to relapsed refractory patients, maybe I can start with Professor Lee. In Korea do you have access to a lot of agents in that situation?

JL: Yes, in the … setting we can choose several kinds of drugs but actually … would use for agents. For example, in the case of lenalidomide we have to use bortezomib previously, so that is the main issue. The other kind of one is we can use freely thalidomide and that kind of drug. So the main limitation at this time is to use pomalidomide for the patient. We can’t use pomalidomide with insurance coverage.
Joy: Pomalidomide you can’t use, OK.

JL: You can’t use pomalidomide with insurance coverage.

Joy: But bortezomib and lenalidomide and thalidomide are available.

JL: Yes, right.

Joy: Do you have a view to how you sequence them or use them in combination?

JL: Yes, it depends on the investigator. So there are two kinds of treatment: the patients treated with previously bortezomib

Joy: You change.

JL: One option is to treat it again with bortezomib treatment, another one is change to lenalidomide instead of the treatment. This option depends on the investigator.

Joy: And in China?

JH: The situation is different for patients. If a patient is young and fit we could recommend he receive allo stem cell transplantation if he can find some donor.

Joy: Does that depend on risk group? High risk or all, the majority

JH: High. Usually the patients are after a lot of lines.

Joy: At first relapse?

JH: For first relapse, first relapse for the patients very young such as less than 40 years. Although they’re first relapsed, yes.  And if he isn’t exposed to novel agents, we could recommend the novel agent. If we use data we could combine the traditional chemotherapy and the newer agents together to get another remission.

Joy: Do you have anything to add?

SY: Maybe I can add our decision tree to what Professor Lee has talked about. We can divide into two categories, for those who are under the age of 65 and over the age of 65. For those under the age of 65 who probably have received stem cell transplantation prior to disease progression they may have been exposed to thal-dex and Velcade and dexamethasone. In that case we can decide on either Velcade re-treatment as long as they have not been experiencing disease progression while on Velcade then we can try Velcade re-treatment on a certain government regulation. And also if the patient did progress on Velcade then this other line, there’s this other line we can apply, lenalidomide dexamethasone. For those over the age of 65 probably they have received VMP as a first line treatment. In that case we can apply a Velcade containing agent in the form of Vel-dex as long as they have been happy with Velcade containing agents. Or other than those two situations we can apply lenalidomide combined with dexamethasone under the reimbursement policy. Under the reimbursement policy so far we have not been able to use pomalidomide as a government funded reimbursement plan. In that case we can use pomalidomide or bendamustine, whatever agents, on patients out of their own pocket. Or sometimes I use low dose chronic use of alkylators such as a daily use of cyclophosphamide, 15mg/day, coupled with dexamethasone 6mg qld. Sometimes that is effective.

Joy: I guess that’s more like a palliative approach.

SL: Yes, it’s sort of palliative. Sometimes you can experience greater response to cyclophosphamide dexamethasone.

Joy: Yes, sometimes you can get a … sure.

SL: Or maybe you can apply melphalan based treatments in the form of MTP or whatever combinations it may be.

Joy: And perhaps I’ll ask with Japan your availability of drugs in the relapsed refractory situation would cover the main novel agents

KH: Yes, actually the end of April this year we got an approval for pomalidomide in the refractory relapsed setting and also the Vel-dex panobinostat is also approved so we can use it in the refractory relapsed setting

Joy: So I can say in Australia we also now have pomalidomide but with the specification that one does have to have been exposed to lenalidomide and bortezomib. I guess one of the big developments that we’ve recently come across is monoclonal antibodies and I would like to discuss your experience with clinical trials or your thoughts about what you heard in the last few days about monoclonal antibodies.
JH: We don’t have any experience in using monoclonal antibodies in the treatment of multiple myeloma.

But from … and from IMW we could know it’s a game changer. Some people say that it may cure the multiple myeloma. We are looking forward to using them for my patients.
Joy: I’ll just mention our experience before I go to the other countries. So we have been involved in the daratumumab trials for relapsed refractory, other centres were also involved in elotuzumab but not my centre. I do agree, even with our limited experience that a lot of us do think it may be a game changer. The mode of action is so different and it seems a very powerful agent. How about Professor Hatake

KH: We finished conducting the second line setting of elotuzumab plus LD and also we just started to have first line chemo for elotuzumab plus LD in newly diagnosed multiple myeloma. Daratumumab is not my centre but definitely the phase I clinical trial has been conducted and we’re waiting for the combination clinical trials

Joy: I might mention, so we’ve completed the relapsed refractory trials and we’re just starting the first line treatment of transplant ineligible patients in combination with Velcade actually, with bortezomib rather than lenalidomide. I think in Korea you have had the daratumumab trials.

SY: In a clinical trial setting.

Joy: Yes.

SY: Outside of the clinical trial setting we have not been able to use daratumumab because it is not available. But in a clinical setting we tried daratumumab in combination with len-dex, lenalidomide dexamethasone. Other than minor infusion related side effects we have seen a very gratifying response, a dramatic response. I think it’s really a game changer. Maybe we may obviate the use of transplantation in the long run if it is so effective.

JL: Most of the Korean doctors didn’t have any experience to use daratumumab as a clinical trial so because the actual Korea started the clinical trial later so just to start these kinds of trials tend to cross the deadline. So unfortunately we don’t have…

Joy: That is a very common finding amongst…

JL: We don’t have any experience to use that kind of drug.

Joy: I guess finally we might talk about what has struck you as perhaps other notable developments in myeloma that you might have learned from this meeting. I’m sure our colleagues in the region would appreciate very much your thoughts about what you think the future may hold. So, Professor Hatake?

KH: OK, actually we have many novel drugs which were conducted in Europe or the United States. But we also are conducting the global trial of as many as possible but unfortunately probably 20-30% of the new drugs come to Japan but not the 70 or 80% didn’t come. That means why the venture company does not have any partners with Japanese pharmaceutical companies so that’s the reason why it does not come to Japan. So this is the reason. And also the age limitation and also the longevity programme in Japan is so strong so maybe the mutation for the chemotherapy takes a while, induction chemo we change a lot. And also we need more drugs because we have a case of a prevalence of leukaemia or extra-medullary disease or myeloma. So drug resistance happens so we must have more drugs to overcome.

Joy: Were there any particular agents that struck you as very hopeful for the future? I guess for Australia we very much would like to see the second generation proteasome inhibitors and one particular problem we have is at the moment we cannot use combinations. With so many of the new drugs, including the monoclonal antibodies as you know, the greatest efficacy is in combinations. So that will be a big challenge for us to be able to use combinations.

SY: Some of the signal transduction may be very promising in the near future.

Joy: Yes, I agree.

SY: Especially combined with currently available targeted agents that already have shown response or activity in the relapsed refractory setting.

Joy: And may I ask your thoughts about MRD, because that’s minimal residual disease that has featured so highly in the meeting? Do you think that will be a big feature of your management in the future?

JL: Yes.

SY: Absolutely.

JL: Yes, definitely.

Joy: Yes, in the research for a cure, I guess.

SY: Coupled with maintenance treatment.

Joy: That’s right, yes. So thank you very much for coming to join this discussion and I’m sure our colleagues would enjoy listening to us. Thank you very much for joining us today.