When taking a pill, receiving an injection, or being infused through a catheter, every multiple myeloma patient or their caregiver has been told to check two simple things: that the name on the medication is correct and that they know what the medication is supposed to do.

Rarely does a patient ask the question, “How much medication are you giving me, and why so much?” If they did, they might be shocked by the answer from the clinician or the oncologist, “That’s how much we give everybody that weighs as much as you do.”

The multiple myeloma patient might then come back with the next obvious question, “Do all people with my weight get the same cancer response and experience the same side effects?” The answer would be, “No.”

In fact if the physician were totally forthright, they would have to admit, “We are not really sure how you will respond to this dosage, but we will monitor you and see what happens. If you experience severe side effects, we will probably decrease the dose. If your response is low and you have no side effects, we will probably increase the dose.” This is called “titrating” the patient. I call it treating the patient as a cancer experiment.

I am a visiting professor of industrial engineering at Purdue University. I am also a multiple myeloma patient. Since being diagnosed with myeloma last year, I visited oncologists for second and even third opinions, attended patient seminars, and read the technical literature about the various cytotoxic agents, cortico­steroids, and novel agents that are available to treat my disease.

Being a scientist, worse an engineer, I was transformed into the dreaded “Internet patient,” one of a class of patients who are the bane of most oncologists-hematologists because of the time they consume in answering various questions relative to prognosis and treatment.

I learned there is an enormous ongoing research effort “searching for a cure” for multiple myeloma. That is wonderful. I also learned that there is much less effort focused on the best way to treat an individual who has the disease, like me. That is terrible. I and 19,999 other individuals were diagnosed with myeloma this past year. We can’t wait for “the cure.” We have to be treated now with the best available agents, using the best dosage regimen possible.

To illustrate the problem, consider the determination of the “standard dose” for the proteasome inhibitor Velcade (bortezomib). In a recent issue of Blood ^[1] (see related Beacon ^[2] news), the results of a Phase 3 randomized clinical trial involving 511 patients showed that administering Velcade once per week instead of twice weekly did not change the efficacy of the treatment, but the side effects were dramatically reduced. Specifically, severe peripheral neuropathy was reduced from 28 percent reported in the group with twice a week treatment to 8 percent in the group with once a week treatment, while 85 percent of the patients obtained at least partial response in both groups.

The results raise two immediate questions?

1. Why did it take us so long to find this result? Surely, many patients have taken Velcade and are probably suffering needlessly because they were overdosed.
2. If cutting the dose from twice weekly to once per week gave the same efficacy with fewer side effects, why not consider reducing it further to say once every two weeks or once every ten days? In fact, why aren’t these dose responses better characterized before a drug is released on the market?

The reason is apparent. Randomized clinical trials are currently used to compare the efficacy and toxicities of various dosages and combinations of treatment agents. They have major drawbacks (see a related Wall Street Journal ^[3] article). They require long time frames and are expensive. Further, with a rare disease like myeloma, there are insufficient patients in the same stage of the disease, with the same pretreatment exposures and even with the same form of myeloma.

Given these limitations of clinical trials, it is not surprising that there is a lack of agreement within the myeloma medical community, not only on dosage regimens but also on how to treat myeloma, i.e., aggressively, moderately, sequentially, or, if asymptomatic, watch and wait. In this opinion piece, I will address only the dosage regimen issue.

As patients, our goal is a dosage regimen that will maximize the effectiveness of treating “our” cancer, while minimizing “our” toxic side effects. The key word is “our,” since each of us responds differently to the treatments.

I have not met an oncologist who does not think that a personalized dosage regimen is a great idea. What I also found among them was a good deal of skepticism that it could be done efficiently without jeopardizing the patient further.

I believe it can be done. The method I am suggesting rests on one basic assumption; there is a relationship between the concentration-time a drug is in the peripheral blood and the efficacy of treatment and toxicities in the patient. It is called pharmacokinetics and is fundamental to the pharmacological basis of therapeutics ^[4].

Why would this not apply to multiple myeloma?

We know that myeloma is in the bone marrow. Drugs find their way into the blood either directly through a catheter or, when taken orally, absorbed from the stomach. The drug or its metabolites are then transferred to the bone marrow microenvironment, where they attack the cancer cells directly (chemoagents) or change the environment to suppress myeloma growth (novel agents). Unfortunately, they are also distributed throughout the body, where they encounter non-diseased tissues and organs, resulting in toxicities.

Each of us has a unique concentration-time or pharmacokinetic profile. By knowing what it is, we can start to determine the best dosage regimen for us.

What would be involved in getting this pharmacokinetic information? Based on our research at Purdue (published in Computers & Chemical Engineering ^[5]), it would require only one, or at most two, blood samples taken at a specific time following administration of a drug. Ideally, these samples would be taken from the patient after receiving an early non-toxic dosage in order to determine his or her pharmacokinetic profile. From these samples and additional data reported to the U.S. Food and Drug Administration by the pharmaceutical manufacturers, a truly “patient-specific” dosage regimen could be calculated before long-term treatment is started.

Why is it not being done today? The approach has not been demonstrated convincingly enough to the multiple myeloma medical community. It apparently would require a major clinical study from a respected medical group committed to finding the best way to administer drugs to the myeloma patient population. Unfortunately, the “Search for the Cure” is getting most of the research funding, relegating “Individualizing the Dose” for us existing patients to a lower priority.

I hope you will join me in encouraging the myeloma medical community to help refocus these priorities so that we can control our myeloma without needless suffering.

Gary Blau currently holds the position of Visiting Industrial Professor of Chemical Engineering at Purdue University. Gary is also a multiple myeloma patient.