Pat’s Place: Are There Too Many Therapy Choices For Multiple Myeloma?
My initial reaction to the question of whether there are too many therapy choices for multiple myeloma is, “What a nice problem!”
It looks like the newest myeloma therapy, carfilzomib, will be widely available to relapsed/refractory patients soon. Pomalidomide shouldn’t be far behind, along with a half dozen new drugs that enhance the effectiveness of Revlimid (lenalidomide) and Velcade (bortezomib).
Soon, multiple myeloma patients may be treated with four-, five-, and even six-drug combinations.
This is a “nice problem,” except for several discouraging things. At least in the near term, even oncologists/hematologists that specialize in treating multiple myeloma will only be guessing when deciding which drugs to use, when, and at what dose.
Timing is everything. And it will most likely take five or more years to begin to sort all of this out, narrowing down the most effective choices for a particular patient at any given time.
Still, I stand by my initial reaction. Choice is good. But with choice comes responsibility:
- Responsibility for the patient and caregiver to learn as much as they can about multiple myeloma therapy options.
- Responsibility to understand when to start or switch to another therapy option.
- Responsibility to understand individualized dosing and what works best for you or your loved one.
In the world of quickly changing myeloma therapy options, all but the best and brightest myeloma experts will find themselves years behind when they sit down to discuss which therapy to try now.
The standard of care for multiple myeloma patients is already years behind. Let me share a couple of examples with you.
Clinicians and myeloma docs are starting to realize that “less is more” when it comes to a number of different anti-myeloma drugs, especially Velcade and dexamethasone (Decadron).
By reducing the dose and/or frequency with which these two important therapy agents are administered, researchers are learning that serious side effects can be significantly reduced, often with very little change in efficacy.
In other words, many multiple myeloma patients have been taking too much chemotherapy for years!
To be fair, it takes time to figure all of this out. Phase 1 studies are designed to determine the maximum dosing a patient can withstand, not the optimum dose.
If we want new drugs to hit the market quickly, dosing miscalculations are to be expected. After all, doctors would rather administer too much of a cancer chemotherapy than too little. It's better for the patient to endure a few extra side effects than to let their cancer spread.
Next week I will share some specific examples of how patients understanding their therapy options can help minimize side effects, while optimizing results.
Until then, feel good and keep smiling! Pat
Pat Killingsworth is a multiple myeloma patient and columnist at The Myeloma Beacon.
If you are interested in writing a regular column to be published on The Myeloma Beacon, please contact the Beacon team at .
Excellent article, Pat. I very much agree with your thoughts about the importance of a patient taking personal responsibility for their treatment. As much as we might feel like it, burying our heads in the sand is not helpful. Thanks for painting a clearer picture for us.
It seems that the more we patients set out to discover the nuts-and-bolts of our disease, the ramifications and side effects of our choices, and the likelihood of potential outcomes, the more confusing it can get. No easy, paint-by-the-numbers system for MM.
My Total Therapy IV trial at UAMS set out to see if the good results found in Total Therapy III could be achieved with less chemotherapy and a different dosing schedule. I'm looking forward to the investigator's findings.
Hi Pat,
I am hoping that the field of cytogenetics along with immunophenotyping will help physicians select the most efficacious agent on an individualized basis.
The dosing issue can also be better targeted on an individual basis now by simply doing pharmacokinectics on patients, something pharmacists are trained to do. I strongly believe every cancer team should have a dedicated oncology pharmacist along with the nurses. Or if it has to be one or the other, I'd take the pharmacist since the nurses job overlaps way more with the doctor, than the pharmacist does who is bringing an entirely different skill set to patient care. Right now every day when patients get aminoglycosides pharmacists monitor& individualize the dose to minimize the side effects. The same can be done right now when it comes to PN, myelosuppresion with chemo agents.
Cancer patients should be demanding that level of care.
Especially, when there are trained licensed professionals with that job already. Why don't we have pharmacists prescribing individualized dosing given the highly toxic nature of many of the chemotherapeutic agents.? Should cancer patients view this as borderline neglect given the diminishment in quality of life that can result from some of the toxicities?
Whether the drugs are new agents or long standing conventional agents...giving a 6ft man the same dose as a 200 lb female that is 5 feet tall simply because they use mg/m2 to dose is simply outlandish. Particularly, when fat tissue is not the same as muscle when it comes to absorption and distribution of the drug. And if the drug is lipophilic deposits in the fat tissue first and then leaches out over time;the man and woman are getting entirely different therapeutic doses due to their different pharmacokinetics. Even though both patients will have the same therapeutic amount in the blood the total amount on board will be different for those 2 individuals.
Phase I studies are designed to determine pharmacokinetics so they tell the maximum as well as effective dose. Along with the rate of elimination and distribution of the drug. They also determine the lethal to effective dose ratio. Something that is essential, if a drug has a very narrow therapeutic index. IOW's the effective dose is very close to the lethal dose making dosing critically important. Drugs such as aminophylline, lithium and clonidine have a narrow therapeutic index.
Overall, Pat...many of the concerns you raised can be eliminated right now by simply adding an oncology pharmacist to the cancer care team. Physicians have expertise in diagnosis and pharmacists have expertise in drugs. Put the two together and we cancer patient will get even better care.
Thanks for raising a critically important issue when it comes to quality of life...we can have more!!
I have met patients where too little was given and it did nothing. We always have to remember that there are many "theories" and that our doctors, as wonderful as they may be, are "practicing" medicine. We viewed it as a joint effort to get us through the maze. Maybe not the shortest route or even the best route, but a route that would get us to the open field successfully.
Hi Pat:
Thank you. Thank you Thank you. The importance of selecting the drugs AND their dosage regimen is vitally important. Unfortunately,unless we change the way we are doing clinical trials your "five years to sort this out" is incredibly optimistic. MM patients need to promote adaptive clinical trials.
The other thing we need to do is promote the use of mathematical modeling to solving this agent selection/dose regimen optimization problem. Docs use archaic non validated concepts like normalized doses (e.g. mg/kg or mg/sq m) since it is easy to weigh someone and measure their height. However,they then give "average" doses to all their patients ignoring the absorption, distribution, metabolism and elimination of the treatment agent from the body. Sadly it is not that hard to estimate how our body handles medicines.It only takes one or two blood samples selected at the right time. They we personalized the doses.
Keep pushing individualizing the dosing concept. All us MM patients need to benefit with the choices available as soon as possible.
Gary
All three of you make excellent points. Thanks for expanding this very important topic--patient quality of life is on the line! Some of this will sort itself out with time. But you know how it goes--the "squeaky wheel gets more done, faster-Pat
Thank you Pat, I'm still waiting for the mieloma treatment. Many oprions but anyone really effective?.
I'm looking forward to see the future therapies; just one that could bring the cure at least for a small percentage.
Pat and everyone else, great points. One of our MM blog members asked a great question. If many drugs are just derivatives of one drug, if one stops working, will the other newer derivatives actually work? EG: If REV stops working, is carfilzomib going to do anything?
Also, where do we stand with genetic testing to determine which chemo might work? I know some of the alternative practioners use it.
Finally, I know they asked me my height and weight before prescribing my chemo a few years back. Doesn't everyone do that? I'm in Ontario, Canada.
Thanks for a great post.
Hanna-
One of the things which excites myeloma docs about carfilzomib and pomalidomide, is the fact they do work in patients that have become resistance to the original drug.
For example, carfilzomib is similar to Velcade, but is reported to work in a number of patients who no longer respond to Velcade. Not all, but some. Similarly, pomalidomide has been reported to work in up to 50% of patients who have already become resistant to Revlimid. Some patients even respond to thalidomide (trade name: Thalomid) after the related, more advanced Revlimid has stopped working.
My take: Myeloma is relatively easy to fool, using even slightly different drugs and/or therapy combos. But--and this is a big but--it may be easy to fool, but it rarely goes away completely- Pat
thanks for that feedback Pat!
One of the things I know that is different about carfilzombib vs bortezimbib(Velcade) is that carfilzomibib binds irreversibly with the cell. I do not know how selective that is. IOW's does it bind only with cancerous b healthy cells? Have not been able to find data on that. Perhaps, the Myeloma Beacon staff can help with that.
Pomalidimide has been shown to have less toxicity than lenalidomide, where myelosuprresion and DVT's are key issues.
Nevertheless, as you stated carfilzomib and pomalidimide are showing efficacy in patients that have relapsed that were on lenalidomide/bortezemib.
Suzie-
All I know for sure is carfilzomib and pomalidomide will give our docs two more major weapons to work with. For relapsed patients, chances are one of them should help, at least for a while- Pat
Yes, I am in agreement that there are 2 new effective agents.
Was hoping to share how and why they can be more effective and less side effects.
Antother key efficacy is that protesome inhibitors have also been shown to overcome some of the cytogenetic abnormalities associated with agressive disease and less overall survival as well as shorter PFS.
Overall, good news for those of us with this chronic disease.
Hope you are having a great Saturday.
I feel like I need a lot of options, right about now. I hope the researchers are working overtime this weekend! Pat
Pat,
You are not alone in needing a lot of options. I do as well. While I am newly diagnosed my cytogenetics are jusr awful according to survival analysis and PFS.
I wish dearly, that someone would look at how to test the MM cells prior to therapeutic decisions, to determine if cells are resistant or susceptible to the chemotherapeutic regimen being selected.. For quite sometime they were saying that t(4:14) was a poor prognostic factor. Then along comes bortezomib and it overcomes that chromosomal swap and patients have better PFS.
Which means that prognostic factors may be related more to the type of therapeutic regimen a patient is put on rather than the disease itself, since bortezomib overcomes the adverse outcome associated with t(4:14).
IOW's the therapy regimen can increase the number of resistant cells, by killing off the susceptible ones, leaving the most resistant OR the therapy could kill off the cells even with poor prognostic factors like bortezomib does.
I wish someone with medical expertise would address this issue cause it is a powerful tool which can be used to extend more MM patients lives.
Happy Sunday!!
Thanks Suzie-
Best of luck to you, too! Pat
How about Acetylon Pharmaceuticals and their new drug ACY-1215 that is being clinically tested for MM???
http://www.acetylon.com/news/press_releases/press-releases-2011/Clinical-Trial-of-ACY-1215-for-Multiple-Myeloma-pr%20.html
I have read about this. Looks promising--like many other developmental anti-myeloma compounds. Let's keep our fingers crossed! Pat
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