COMy 2018 | Affordable and effective strategies in myeloma: do they exist?

The 4th World Congress on Controversies in Multiple Myeloma (COMy) was held in Paris, France, from 3–5 May 2018. The final session of the congress took place on Saturday 5 May and was moderated by Thierry Facon, from Lille University Hospital, Lille, France and Mohamad Mohty, from the Saint-Antoine Hospital and University Pierre and Marie Curie, Paris, France. Vincent Rajkumar from the Mayo Clinic, Rochester, US, presented one of the most eagerly anticipated talks of the meeting, on the topic of the high cost of multiple myeloma (MM) treatments.

Dr Rajkumar began by thanking the organizers for the opportunity to present, explaining that the high cost of drugs is a widely recognized problem worldwide and is therefore not a topic of debate, but one to be reconciled. The scene was set with the presentation of an ideal treatment algorithm for MM (see Figure 1. from Next-generation multiple myeloma treatment: a pharmacoeconomic perspective). Some key facts were then presented.

In the US, there were 30,000 newly diagnosed (ND) MM patients in 2017, with a total lifetime cost of treatment amounting to $22.4 billion, excluding other costs such as time spent in the hospital, infusions, imaging, nursing/physician costs, and ancillary costs. Dr Rajkumar explained that all the drugs currently available are expensive and that the cost of even basic drugs has risen in recent years. He used the example of cyclophosphamide which previously cost $416 but now costs $5,800. When regimens are combined in triplet/quadruplet regimens, inevitably the total cost increases further. Actual drug costs per year were presented - see below:

Abbreviations: VRd = bortezomib, lenalidomide, dexamethasone; KRd = carfilzomib, lenalidomide, dexamethasone; VCd = Bortezomib, cyclophosphamide, dexamethasone; DRd = daratumumab, lenalidomide, dexamethasone; D-VRd =  daratumumab, bortezomib, lenalidomide, dexamethasone; D-KRd = daratumumab, carfilzomib, lenalidomide, dexamethasone

To put the costs into perspective, a tangible example was used: "for the cost of one week of VRD you could buy two of the latest iPhone 10’s, and would still have extra money to buy all of the old models plus top of the range headphones and other accessories". This extremely high cost is the case for all the drugs currently used to treat MM, as well as new drugs on the horizon, including CAR T-cells.

Dr Rajkumar explained that the same story is also playing out in other cancers too, and will, therefore, affect all of us. The hard-hitting fact that one in three people will get cancer in their lifetime was used to drive the message home, along with the fact that all new cancer drugs approved by the FDA in 2014 now cost more than $120,000/year. "Taking an average annual household gross income in the US into account ($52,000), four people would have to work in order to pay the bill for one person’s cancer therapy".

These extortionate costs do not only apply to new drugs, long-standing drugs have also been subject to price rises. Dr Rajkumar gave the example of Daraprim, used to treat a life-threatening parasitic infection, which increased in cost overnight from $13.50 to $750, for one tablet. The drug was manufactured by Turing Pharmaceuticals, led at the time by Martin Shreli, who saw an easy way to increase profits overnight. Indeed, this decision though arguably criminal in its inception, was actually perfectly legal and Dr Rajkumar explained that this is part of the wider problem. Using growth curves to provide a view on how the cost of living in terms of various consumables has changed in the last 20 years, the dramatic upward trend in the cost of drugs was illustrated, while, for example, the cost of technology, has dramatically decreased. Dr Rajkumar showed how insulin, in particular, has risen astronomically, and posed the question, “So why are drug prices so high?”

So why are drug prices so high?

The number one reason was attributed to the fact that drug companies have been given a monopoly in the form of 10 years’ patent protection, even on life-saving drugs. This is also the case for drugs to treat myeloma, which is currently not curable. "The drug companies know that even drugs indicated for use at a late stage will be needed at some point". Dr Rajkumar explained that drug companies are adept at sustaining this monopoly by what he described as “blatant and occult patent ever-greening”, through careful marketing that continually ensures delivery of the message that the newer or latest drugs are better. The big companies will also regulate the arrival of generics, by paying off those companies so they cannot introduce their drug to the market.

The cost of drug development is also now extremely high, because we as the consumers insist on “such perfect data, and generating this perfect data will take hundreds of millions of dollars”. Finally, Dr Rajkumar talked about ‘the seriousness of cancer’ saying, “This is what bothers me the most. Cancer is such a serious disease, myeloma is such a serious disease, that we are willing to do anything for a loved one. And people are prepared to pay whatever it takes. Countries are prepared to do whatever it takes for their citizens”.

Dr Rajkumar went on to further explain why the prices of drugs in the US, in particular, are so “insanely high”. He began by explaining how Medicare, which has drug purchasing power in the US, is not legally allowed to negotiate on price. This differs from similar purchasing bodies in Europe for example, where the health authorities will ensure rational pricing based on drug benefits. There is also a ban on personal importation in the US, and bringing drugs into the country is illegal. Thirdly, Dr Rajkumar explained how the US system of reimbursement encourages physicians to prescribe the more expensive option, as they are given a certain percentage (up to 6%) of the total cost of the drugs for their own financial gain. If two drugs are equally effective, physicians in private practice will more often choose the more expensive option to benefit themselves. There is also liberal off-label use where physicians can use drugs that are approved for other indications to treat myeloma. Finally, there is no equivalent of a health authority in the US, which would negotiate and legislate drug use by providing clear-cut guidelines for drug prescription.

Dr Rajkumar also spoke about “a lack of allies”, as very few physicians are willing to challenge pharma because they benefit personally from high prices. Many physicians are also taking honorariums and rely on pharma for funding their own research. In addition, very few professional organizations and societies are prepared to talk about lowering prices. Whilst it might be assumed that patients would take up this cause, Dr Rajkumar explained that the patients that are receiving drugs often aren’t paying themselves as it is covered by their insurance, and those that aren’t covered are often too disadvantaged to protest. The insurance companies have also reacted by simply increasing their premiums, and as long as the price hikes are slow, then they can cover their costs.

So, what can we do?

Solutions unique to the US include establishing a value-based pricing system, which will allow Medicare to negotiate prices, and the US needs to allow importation for personal use on the free market. All countries can facilitate easy entry of generics and biosimilars to generate real competition. The example of Poland was then given, where imatinib is sold at a very low price because there are 19 generics driving true competition. However, Dr Rajkumar recognized that most of this is beyond the average physician and provided more practical means of action:

• Choose the best option. Sometimes you can make compromises eg. ACD or VTD instead of VRD, and limit maintenance to 1-2 years, or use consolidation instead of maintenance.
• Recognise that US drug prices matter worldwide. The US market accounts for 46% of global cancer spending, which is more than $100 billion per year. Dr Rajkumar explained that in smaller countries, such as France, the bigger drug companies can walk away from price negotiations because they can always make up that share in the US by increasing the price. Therefore, what’s happening in the US can have a direct effect on other countries worldwide.
• Generate careful, powerful guidelines, and take responsibility for speaking at congresses. He emphasized that “what we say matters”, in particular, what is said on a platform at a conference and labeled as a ‘standard of care’, as this could be translated into decision-making in the rest of the world. Dr Rajkumar stated: “National guidelines combined with the US reimbursement system make it easy to justify the more expensive option”, adding “the ease of off-label use facilitates this”.

Examples of triplet and quadruplet regimens were used to illustrate how increased cost can benefit the prescribing physician, and indeed research has shown that clinicians in the US, in general, are prescribing the more expensive option. Dr Rajkumar spoke about the responsibility of physicians talking at conferences “to recommend carefully”, adding “for example do not recommend denosumab for all patients as it is 10-20 times more expensive than zoledronic acid”. He also emphasized the need to make a distinction between data that can be used for approval, such as an experimental regimen versus no treatment, and the use of this data to push a regimen into frontline. “We need to be careful with what we say and how it can be interpreted so that people get the right message”.  

Finally, Dr Rjkumar spoke about advocacy and referred to a paper published in The Lancet which he co-authored with Philippe Moreau: 'Multiple myeloma – translation of trial results into reality', which called for strategic trials. Such trials “should be designed to examine cost, access to drugs, side-effects, and quality of life”. They should be designed so that the results matter in real-world scenarios, in particular, to predict therapy duration, as shorter durations will inevitably reduce cost. He explained that providing 6-12 months of therapy and stopping, should be the long-term goal and that patients need to be assessed individually.

Dr Rajkumar concluded that we can all fight for lower drug prices, but emphasized his stance that “this is not a fight against pharma, and it is really not right to blame them, because pharma are really only doing what the law allows”. He used the amusing analogy of a jar full of candy, with the parents (the government), telling the children (pharma), that they can help themselves and eat all they want, then someone (the physicians) coming in to tell them not to eat it because it’s not good for them.

The conclusion was that the law needs to change in order to have reasonable drug prices going forward, with access to drugs being another big issue to address. Dr Rajkumar conceded that in reality most clinicians will be torn between the morals of a physician in wanting to choose the best possible option for their patient, and the moral requirement for society and the need to think about cost.

The ASCO committee chose to address the question of affordability in a debate as part of the session covering ‘Global Myeloma, Health Disparities and the Cost of Drugs’. The debate, on the topic of ‘Value and Cost of Myeloma Therapy’, took place on 3 June between Vincent Rajkumar (@VincentRK) arguing ‘we cannot afford it’ - listen here to a summary, and Rafael Fonseca (@Rfonsi1) arguing ‘we can’ - listen here.