Multiple myeloma analysis from ASH 2017

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Published: 12 Dec 2017
Views: 3305
Dr Maxim Solovev and Dr Sung-Soo Yoon

During this expert discussion, Dr Maxim Solovev from National Research Centre for Haematology, Moscow, Russia and Dr Sung-Soo Yoon from Seoul National University, Seoul, South Korea and looked at the impact recent data releases, from the 59th annual American Society of Haematology conference in Atlanta, would have on patients living with multiple myeloma.

During this session, the two clinicians discussed abstracts that covered treatment strategies for newly diagnosed multiple myeloma (NDMM) and relapsed or refractory multiple myeloma (RRMM), including daratumumab plus lenalidomide and dexamethasone (DRd), lenalidomide plus dexamethasone (Rd), and from the APRIL study and results from trials including ixazomib as a treatment option.

This programme has been supported by an unrestricted educational grant from Takeda

Dr Maxim Solovev - National Research Centre for Haematology, Moscow, Russia
Dr Sung-Soo Yoon - Seoul National University, Seoul, South Korea

What abstracts or sessions have caught your eye during Ash 2017?

SSY: I’ve seen a lot of clinical and research data in multiple myeloma, sort of actually inundating data, mostly on targeted therapies including monoclonal antibodies as well as CAR T-cell therapy and new targeted agents aiming at specific newly developed, newly found signalling strategies and pathways. Therefore, the armamentarium against multiple myeloma will be expanding ever and ever and eventually I get a glimpse that someday multiple myeloma will be a curable disease. Once it has, until now, technically only a minority of them do enjoy long-term disease free survival but in the end or the first coming years multiple myeloma will transform into a curable disease with a variety of therapeutic intervention technologies.

MS: Now we open really a new area for myeloma treatment named as immunotherapy because after ten years when we start to use monoclonal antibodies for first line therapy myeloma patients we will really introduce progression free survival and overall survival. Because if you can see and remember the outcomes of the POLLUX study or CASTOR study, we know it’s very good results for progression free survival and for patients who receive daratumumab for relapsed therapy it’s good results. And the next part of myeloma treatment in the future will be CAR T-cells and will be associated with CAR T-cell therapy. Now in this ASH we can see really a lot of preclinical studies for CAR T-cell therapy, a lot of disease, haematological disease, including myeloma. And biclonal antibodies, a very interesting idea, now we know it.

Can you tell us about the abstracts that you have been involved in at ASH 2017?

MS: We researched the duration of MRD negative status after autologous stem cell transplant in myeloma patients. We researched MRD with flow cytometry every three months for progressive disease without maintenance therapy, patients don’t have maintenance therapy. Our results, we have now 60% progression free survival for lost MRD negativity status after autologous stem cell transplant for three years. More interesting, treatment free survival – now only one patient we use next line therapy, 90% of patients don’t have therapy for three years. I think it’s very interesting results and now we have this important knowledge here. When we have it we have another randomised clinical trial for patients with a complete remission after autologous stem cell transplantation. We randomised patients for two arms – arm A maintenance therapy, lenalidomide only for one year, and arm B observation. For next year’s ASH we will introduce our result because our analysis now we have really good results already now.

SSY: I authored and co-authored several abstracts on multiple myeloma but I’d like to mention just one of them because this has been studied in Korea as a retrospective patient. Even though it is a retrospective study it covers almost all myeloma patients who have been treated with lenalidomide and dexamethasone using national survey registry data. The bottom line is among them we have been achieving very good partial remission, obviously did better than other people. Again, for those who have been able to receive more than four cycles of lenalidomide dexamethasone also did much better than those who have been unable to receive fewer than four cycles. Again, by adequate adjustment of dose for those who have mild renal dysfunction they were able to tolerate lenalidomide dexamethasone for an extended period of time. They have enjoyed a rather long, more than several years, of disease free progression free survival. Also for those patients who have fewer comorbidities did fair again. Therefore it is, as you can see in this ASH meeting, as an analogy to our data one of the papers has described long-term outcomes of currently available cutting edge proteasome inhibitors coupled with immunomodulators such as KLD, VLD and ITD. If we compare in a real world situation, real clinical situation, for those who have been treated with the three regimens such as KLD, VLD and ILD, strikingly and surprisingly those patients who have been treated with the most moderate regimen, ILD, did much better than the other two groups who have been treated with KLD and VLD. What does that mean? It means that even though the clinical outcome on a research basis in a very limited and very strict patient eligibility criteria, even though VLD and KLD seem to be much more superior to ILD, in the real world the less toxic ILD conferred much more benefit to patients who have been treated with the combination of a proteasome inhibitor and the immunomodulator. Therefore this gives us a feeling that if lenalidomide, even though it seems to be less active than proteasome inhibitors such as carfilzomib or bortezomib, ILD, if it is adjusted according to the patient’s condition, will help patients enjoy a meaningful life without having any significant side effects.

How do you plan to implement this into your clinical practice?

SSY: Multiple myeloma is a chronic disease that requires prolonged, less toxic treatment. Lenalidomide is one of the ideal agents that can be applied for an extended period of time for those patients who will have a prolonged disease course. The bottom line take home message is that lenalidomide dose and administrative schedule should be tailored according to the patient’s own condition.

How would patients access CAR T therapies in Russia?

MS: Now it’s not possible, it’s impossible in Russia. I talked about CAR T-cell therapy but in the future why not. Now we have a lot of clinical trials, the whole world has, but in Russia we don’t have these clinical trials about CAR T-cell therapy. But after ten or fifteen years we will use CAR T-cells for our patients, more patients will get CAR T-cell after ten years.

Is there any data that you are looking forward to in the coming years?

SSY: Because CAR T therapy has been so effective in eradicating tumour cells there should be much wider application of CAR T therapy for those who have relapsed and refractory multiple myeloma. In addition there are a bunch of new agents that are very active in the RR setting, relapsed refractory setting, therefore the outcome of multiple myeloma patients will be improving much better at a treatment speed. Eventually autologous stem cell transplantation will give way to non-transplantation approaches. Again, in that context autologous tandem transplantation might disappear pretty soon because the second transplantation, allo and auto transplantation, will be replaced by whatever more effective treatments such as CAR T and Selinexor or venetoclax and so on and so forth. So patients will enjoy disease free survival with fewer, much safer treatment modalities.

MS: Next year I think we will know the results of the IFM group study for daratumumab induction and transplant patients and maintenance therapy daratumumab. I think it’s very good results but we will know it. In next year’s ASH we will know the first results for new genome sequence and first results for each mutation and we can use one drug, for example bortezomib if we see this one mutation and maybe lenalidomide if we see another mutation. It’s our future and maybe the next ASH we will know it.

How do you manage patients with multiple myeloma in your countries?

MS: From our information in our country, in Russia, we have almost ten thousand myeloma patients. Now we have epidemiology trials including three thousand newly diagnosed myeloma patients and we know in the first line therapy we use bortezomib in 95% of patients. For second line therapy we use lenalidomide with combination, for example dexamethasone and cyclophosphamide and other haematology drugs. It’s almost 70% of people have lenalidomide and dexamethasone. These drugs, bortezomib and lenalidomide, include a government programme for seven diseases and absolutely free for all patients but after a year we have a problem because it’s a very big cost, for example daratumumab, pomalidomide, carfilzomib, ixazomib, elotuzumab, and we have to optimise our therapy for myeloma patients but it’s our future and I believe it.

SSY: Outside of clinical trials we have been able to used Velcade based treatment for our newly diagnosed multiple myeloma patients based on the availability of transplantation approaches. Under the age of 65 those patients that are transplantation eligible because of the reimbursement policy imposed by our government then we can prescribe VTD, Velcade thalidomide dexamethasone, or VD, Velcade dexamethasone. But as of December of this year we were allowed to prescribe len-dex, lenalidomide dexamethasone, as first line treatment. Therefore we can prescribe either a Velcade containing regimen or lenalidomide dexamethasone as a first line treatment. For those who are ineligible for transplantation approaches, as in the VISTA trial, we have been prescribing VMP, Velcade melphalan dexamethasone. But as of December of this year we are able to prescribe len-dex again in this population. In second line treatment if we applied a Velcade containing regimen then literally len-dex will be our second line regimen and the third line regimen will be pomalidomide dexamethasone with or without cyclophosphamide. But if we happen to prescribe len-dex as a first line regimen for both groups then probably we may run into problems choosing several options – one is VD, Velcade dexamethasone, the second option is a Kyprolis based one. Most likely if the patients have been exposed to len-dex then we will be able to prescribe KD, Kyprolis, carfilzomib, and dexamethasone. If the patients have been exposed to Velcade containing agents such as VTD or VD or VMP in the case of transplant ineligible patients then we may resort to KLD that contains lenalidomide as one of its treatment constituents. We can freely prescribe other agents but the problem in including the ones such as daratumumab it is not reimbursed yet by our government. The patients themselves have to pay from their own pocket but our Korean government FDA has allowed us to prescribe it for the patients who are suitable or who will benefit from daratumumab use or whatever agent it may be.