One of the lessons I have learned over time is that models are really valuable for making sense of things in life.

Now, the sort of models I have in mind aren’t the kind you build with plastic pieces and glue, or the kind you see in fashion shows.

The models I’m talking about are simplified versions of the real world, with the simplifications specifically designed to highlight the most im­por­tant features of whatever it is that’s being modeled.

Given their pur­pose and design, I guess it’s not entirely surprising that models can be so valuable.

In basic chemistry and physics, for example, you can get a lot of mileage out of thinking about atoms as miniature solar sys­tems.

Similarly, in economics, supply and demand are always a good starting point.

Psychology has the id-ego-superego model of the psyche. Business has the five forces model of corporate strat­e­gy. Astronomy had the (now discarded) geocentric model of the universe.

Models separate the wheat from the chaff, helping us focus on what’s im­por­tant. They’re like the movie version of a long novel; you get the main plot and main characters without the distracting side stories and countless bit players.

But what model should we use to help us under­stand multiple myeloma?

To be honest, in the 15 years I’ve been researching, discussing, debating, and reporting about multiple myeloma, I have yet to come across a good, practical model of the dis­ease. About the closest thing I have found is some of the research about evolution and how it applies to multiple myeloma ^[1]. Yet, as valuable as that research is, I don’t think it offers the sort of framework that patients and medical professionals can use on a regular basis.

This is unfortunate. The lack of a practical model makes the dis­ease much more confusing and mysterious than it needs to be. This confusion isn’t just an inconvenience. I believe it has a real impact on the quality of care multiple myeloma patients receive.

That’s why I’d like to remedy the situation a bit by describing the basic version of a model I’ve devel­oped. It covers not just active (symptomatic) multiple myeloma, but also smol­der­ing multiple myeloma and mono­clonal gam­mop­athy of undetermined sig­nif­i­cance (MGUS).

I will admit that the model may seem odd at first, perhaps even crude or overly simplistic. I also will admit that this is the first time I’ve shared the model with a broader audience, so flaws may come to light that need some polishing.

That being said, I think you’ll find the model offers helpful insights, especially if you dig into it a bit, probing it here and there with questions.

The Basic Faucet And Tub Model

The model simplifies a person’s health and the myeloma dis­ease process by asking us to think of a person’s body as a tub and the dis­ease process as a faucet.

In a person who has neither myeloma nor MGUS, the tub (their body) is empty of myeloma cells, and the faucet is closed.

In some people, how­ever, the faucet loosens, and myeloma cells start flowing into the tub. If the flow of cells entering the tub is not too high, the body’s immune response – the drain in the tub – can handle the dis­ease, and the tub stays empty.

In some cases, the immune response is not enough to handle the faucet flow, and myeloma cells start accumulating in the body. When the accumulation of cells is very low, you have MGUS. When it is a bit higher, you have smol­der­ing myeloma. When it is even higher, you have symp­tomatic multiple myeloma.

If nothing is done to empty the tub (body) of myeloma cells, the tub overflows. The body is overwhelmed by the dis­ease.

Fortunately, myeloma can be treated, and myeloma treat­ments in the model are depicted as buckets. In the basic version of the model, each bucket rep­re­sents the full effect a single treat­ment can have on a person’s dis­ease, so there is one bucket for each possible treat­ment.

One bucket, for example, might rep­re­sent Velcade (bor­tez­o­mib) and the impact it can have when a patient is treated with the drug until their dis­ease no longer responds to it. Another bucket might rep­re­sent the full impact Darzalex (dara­tu­mu­mab) can have, a third bucket might rep­re­sent mel­phalan, and so on.

When a bucket (treatment) is used, it lowers the level of cells in the tub (body). This response to treat­ment causes a period of time when the level of cells in the tub are low (remission), and it extends the patient’s survival by lengthening the amount of time until the tub overflows.

Some Quick Insights From The Model

What I have just described is the basic version of what I call the faucet and tub model of multiple myeloma. In my next column, I'll describe a slightly more complex version of the model, one that many researchers would argue is a better reflection of reality.

I'd argue that's up for debate. I'd also say we shouldn't downplay the insights to be gained from the basic version of the model. Allow me to list two that spring to mind.

Treatment options – The basic model underscores just how im­por­tant treat­ment options are for the survival of myeloma patients. More treat­ments (buckets) lengthen the time a patient has until their dis­ease can't be stopped. Myeloma patients today are surviving longer than patients 25 years ago because they have many more “buckets” to keep their “tubs” from filling up with myeloma cells.

Note, how­ever, that the lesson here is not just a big-picture lesson about the survival of myeloma patients in general. There’s also a lesson for in­di­vid­ual patients.

In particular, if an in­di­vid­ual myeloma patient wants to maximize their survival, they need to avail themselves of as many effective and safe treat­ment options as possible, and they need to exploit each option to the fullest extent possible.

This won’t be the case, though, if older myeloma ther­a­pies are excluded from con­sid­er­a­tion, if creative com­bi­na­tions (such as nelfinavir and Velcade ^[2]) are off the table, and if there are no plans for the patient to par­tic­i­pate in clin­i­cal trials testing poten­tial new myeloma ther­a­pies.

Treatment response, length of remission, and over­all survival – The basic model also ex­plains why multi-drug ther­a­pies almost always lead to deeper treat­ment responses and longer remissions. Two or three buckets will scoop out a lot more cells, and lower the level in the tub a lot more, com­pared to what a single bucket can do, thus in­creas­ing the time a patient is in remission (that is, the time it takes for the faucet to fill the tub back up to a high level).

Note, how­ever, that the model also highlights why you can’t nec­es­sar­i­ly assume that deeper treat­ment responses and longer remissions automatically lead to longer over­all survival. Using more drugs to get a deeper response has, with this version of the model, a kind of “robbing Peter to pay Paul” effect.

If you use two buckets (treatments) instead of one, you will get a deeper response and a longer remission. However, you also will have one less treat­ment option at relapse.

So in this version of the model, multi-drug treat­ment leads to deeper treat­ment responses, but the deeper responses do not lead to longer over­all survival. The version of the model I’ll discuss next time, on the other hand, allows for a possible im­prove­ment in survival.

Putting The Model Through Its Paces

There are many addi­tional appli­ca­tions of the basic version of the faucet and tub model, and I en­cour­age you to explore them. How would you use the model, for example, to ex­plain high-risk versus standard-risk multiple myeloma? What does the model say about treat­ment sequencing? Does it have any­thing to say about main­te­nance ther­apy or au­tol­o­gous stem cell trans­plants?

As you explore the model further, I am sure you’ll find predictions it makes that don’t seem right to you. When that hap­pens, keep in mind that one of the pur­poses of the model is to help us under­stand why our assump­tions are what they are, and whether the assump­tions, or the model, need to change.

———————————— ♦ ————————————

This is the first in a regular series of columns I will be writing for The Beacon. As the Beacon’s founder, it’s been my pleasure to be involved in the preparation of many of the articles and announcements you can find here. I will con­tinue to make similar con­tri­bu­tions in the future, but I also will be sharing in these columns some of the broader perspectives and insights I’ve gained during my tenure in the myeloma com­munity.