Multiple myeloma highlights from ASH 2017

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Published: 12 Dec 2017
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Prof Meral Beksac - Ankara University Medical School, Ankara, Turkey

Professor Meral Beksaç, a haematologist from Ankara University, Ankara, Turkey, spoke to ecancer about treatment options for patients with Multiple Myeloma (MM) at the 59th annual American Society of Haematology conference in Atlanta.

Professor Beksaç started off by discussing the reclassification of smouldering MM, and highlighted a study, presented by Craig Hofmeister, where patients were randomised into three arms receiving either a long, intermediate or short dosing schedule of singe agent daratumumab. The estimated 12-month Progression-Free Survival (PFS) rates were 98%, 93%, and 89% in long, intermediate, and short arms respectively, and Professor Beksaç concluded that it was possible to achieve Very Good Partial Response (VGPR) rates with early interventional treatment in MM patients.

The conversation then featured the EMN02/HO95 study, presented by Dr Michele Cavo; an international trial that was conducted with the European Myeloma Network, that initially enrolled ~1,500 to receive either four cycles of bortezomib-melphalan-prednisone (VMP) vs High-Dose Melphalan (HDM) with Autologous Stem Cell Transplantation (ASCT). The 3-year PFS results for this study was 61% for all patients. The updated results of this study, also presented by Dr Michele Cavo at ASH, found that patients randomised to receive two ASCT was superior over one ASCT in terms of prolonged PFS and Overall Survival (OS), which confirms the necessity to consider transplants as an option to improve patient outcomes.

Finally, Professor Beksaç discussed how patients are becoming increasingly aware of the treatments available on the market to treat MM, with some even attending conferences such as ASH. Professor Beksaç stated that it was important for patients, as well as the wider healthcare community, to be educated on the most exciting data from global conferences as it could lead to a patient’s MM being identified earlier, offering them a better chance for their disease to be managed and controlled. Professor Beksaç also discusses the initiatives that she is involved with to help educate the community in her home country of Turkey.

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

It’s very hard to distinguish between the best because there is so much good data being presented here but regarding multiple myeloma treatment the options for the current drugs which are newly approved in some countries but not yet approved in other countries, mainly monoclonal antibodies, that’s very appealing. Of course transplant is the ongoing question that’s always addressed, the second part, which is also very attractive but furthermore the basic science on the genesis of multiple myeloma that’s evolving very fast and we have now new targets which means new drugs which are in the pipeline. So these are all important topics that are attractive to us.

What are the best practices in order to monitor and identify patients with Smouldering Multiple Myeloma?

The thing is, during the last two years the definition of multiple myeloma has change and earlier patients with ultra-high risk smouldering multiple myeloma are now considered as multiple myeloma. So some studies which were initiate earlier addressing smouldering multiple myeloma have two new categories which are high risk and intermediate risk. There is a smouldering multiple myeloma study that we were included in and the results were presented last evening by Craig Hofmeister. It’s an international study using single agent daratumumab with short, intermediate and long-term use and even with single agent daratumumab in the early phase of multiple myeloma it was possible to have VGPR – in the short use about 15% and in the long term use 29%, double. So this is a good study which implicates early intervention of smouldering myeloma before the SLiM criteria appear. So, like ten years ago we were always promoting and advising that we should not treat multiple myeloma early because the drugs were not of sufficient efficacy and did not have an impact on outcome but nowadays the newer drugs with higher safety profiles and very effective outcomes, the trend, maybe the philosophy of treatment of myeloma, is changing.  The thing is how to recognise those patients who have the potential to progress within a short period of time. The recent definition of multiple myeloma has enabled us and there are studies which have a bigger aim, such as cure attempt, in smouldering multiple myeloma and that’s another important study which was presented by the Spanish group, by Marivi Mateos. Instead of molecular antibodies they have implemented a new proteasome inhibitor which is carfilzomib with lenalidomide plus dexamethasone. After induction and stem cell transplant and a consultation they are able to achieve very high complete response rates. So maybe hopefully with a longer follow-up they might be able to cure myeloma earlier in the course of the disease without having the bone disease or renal or other tissue organ damage that are, most of the time, irreversible.

Can you please give an overview of your abstracts?

There is an oral presentation, or it was presented yesterday actually by Michele Cavo that’s the international collaboration we have with the European Myeloma Network, that’s the EMNO2 study that enrolled 1,500 patients. It’s a huge study. When the study was planned drugs such as bortezomib and lenalidomide had entered the field and they were so promising that the role of stem cell transplant was questionable. So the aim of the study was to compare a VMP type of regimen, which includes bortezomib and melphalan but in the standard dose, four cycles, versus stem cell transplant. So it’s stem cell rescue versus no stem cell rescue, more intense melphalan, less intense melphalan, with a similar induction regimen and there were two randomisations. The first randomisation is the updated results that were shown yesterday by Michele Cavo, again confirming the importance of stem cell transplant.

Subsequent in the same session, in the stem cell transplant session, there was another presentation by Michele Cavo, this time comparing one transplant versus two transplants. The winner is the second transplant, two transplants but if you look more carefully in the data those who are benefitting and upgrading their response with the second transplant are mainly those with high risk features. Overall the impression is now for standard risk patients one transplant is essential but for only those with high risk a second transplant is a confirmed finding that the clinical practice will be affected. So the transplant session yesterday with our data, with our contribution, is becoming more and more important and, of course, it’s the least expensive treatment modality compared to the newer agents which most of the time are very expensive. We must not also use this modality more than it is required so one transplant, currently, is required so our contribution is underlined in this manner.

Both our other abstracts are based on the same study. There is a poster today looking at the renal impairment and the impact of treatment on the reversal of renal impairment and here again bortezomib presented by the first author, Thanos Dimopoulos, it is shown that reversal of renal impairment is possible. We have another abstract but that’s for publication only but that’s from Turkey and it’s our national experience with daratumumab as a single agent but this time in relapsed refractory myeloma. So this is the indication which is approved for Europe currently and the approval is pending in Turkey. We have observed within 40 patients, it’s a small study, it’s a prospective evaluation, there are two CRs and one VGPR which for a median five prior lines of therapy this is a very good experience. It’s exactly what has been observed with the SIRIUS trial, the initial trial of single agent daratumumab. So newer agents are life-saving for patients who have experienced multiple relapses. We are looking forward to having approval of these agents and also introduction of even more newer ones.

There is another one which is approaching to approval which is venetoclax. We have no data so far from our own experience but the data which was presented last year and also this year, this drug is targeting BCL2 which is not specific for multiple myeloma but for AML and for other disorders. It’s amazing that an oral formulation can target BCL2 whereas earlier, many years ago, we were trying to have antisense oligonucleotides to address or target BCL2, now it’s an oral formulation and I’m sure it’s going to be approved very soon.

How do you see these novel agents impacting clinical practice in Turkey?

The thing is that patients are now more aware of what’s going on and they follow the congresses. I’ve seen patients attending the ASH meeting also from Turkey, earlier, not this year. But they follow the slides that we share with our colleagues regarding, for instance, amyloidosis which is also another plasma cell disorder. When they hear about the monoclonal antibodies being so successful, starting with daratumumab and there’s another one which is NOD-001 [?] and another one which is targeting the amyloid fibrils, so this information is very appealing. Patients have now started to push authorities to have the accessibility to these drugs. For rare disorders this should be successful because it doesn’t address a big population and the cost is not the issue here but it’s saving lives. When it comes to amyloidosis Professor Merlini here received a very prestigious award two days ago for his achievements and contributions to the field of amyloidosis. As he pointed out very clearly, early recognition of the disease is the most essential factor because then the treatment is even more successful than multiple myeloma. For early recognition we need the help of patients, patient support groups, and also the awareness among the physicians extends beyond haematologists who are attending this type of meetings. But we need to outreach to neurologists, cardiologists, nephrologists who are seeing these patients with the first appearance of symptoms.

Do you receive patients that request particular or specific treatments?

That is always what’s happening and sometimes they present logical data, sometimes some of them are very irrational. But of course we have to respect their search on the internet and to be able to provide them with accurate information. In our country we have built up websites for addressing patients and in our institution we do monthly educational seminars for patients. On my return on 25th December I’m going to give them an update on our experience here at ASH. We do tape them, we put on our website so that people who are not able to attend from other cities can also follow.

What data are you looking forward to seeing in 2018?

Today and yesterday I was attending sessions on the molecular biology of myeloma and with the introduction of new molecular techniques such as genome wide sequencing and copy number variations which have now become more widely applicable. Then there is data on patients and the heterogeneity among patients and not only at diagnosis but during the course of the disease and following treatment. So now we are able to see the dynamic changes at the molecular level, not at much sensitive levels compared to the cellular differences. This gives us the opportunity to detect targets which have the potential to use new drugs, not for everybody but for those who have the targets. So this will save us from toxicities, unnecessary toxicities, and increase the efficacy. But the danger lies also the cancer cells are very clever cells, once you target one mutation or one receptor eventually that may disappear but newer receptors and the cancer cells will survive with different mechanisms is a possibility. So we have to go to the real initiating factors to be able to target the real target. So for the future, based on the advances in the molecular biology we will be approaching the real core of the mechanism and there are signs that this is very promising. Furthermore, not only the molecular genetics but software people, the computational analysis, that’s also evolving and that’s another aspect which complements two areas. At the end, the computational analysis sometimes predicts the in vitro tests so it saves you from lots of energy, lots of expenses and speeds up your plans. So these are really very promising areas.

I would like to thank you for giving me the opportunity to express my thoughts and my experience and also from the perspective of Turkey and the Turkish patients and physicians. It’s been a wonderful opportunity. Thank you.