The cure versus control debate

S. Vincent Rajkumar, MD, of the Mayo Clinic, wrote a very interesting article last fall about the cure/control issue (see: Two fundamental questions: Should we treat patients with myeloma with multidrug, multitransplant combinations with the goal of potentially curing a subset of patients, recognizing that the risk of adverse events and effect on quality of life will be substantial? Or should we address myeloma as a chronic incurable condition with the goal of disease control, using the least toxic regimens, emphasizing a balance between efficacy and quality of life, and reserving more aggressive therapy for later?

The ensuing paragraph confirms that there is no cure for myeloma. Ok, we already knew that. What we have instead is what is called “complete response” or CR. Now, I should note that quite a few studies have demonstrated that CR is not relevant for the vast majority of myeloma patients in terms of overall survival (see, for instance: And Dr. Rajkumar essentially seems to agree: Cure vs control is debated because the strategies currently being tested are not truly curative but rather are intended to maximize response rates in the hope that they will translate into an operational cure for a subset of patients. Not very encouraging…

Dr. Rajkumar then provides a history of myeloma’s conventional treatments. CR was rare before the 1990s. Back then, Cure was never a goal of therapy because it was assumed to be unattainable. The goal was instead to control myeloma and keep the patient alive for as long as possible with a minimum of toxic side effects.

Then, in the 1990s, he writes, high-dose therapy with autologous stem cell transplant (ASCT) became part of standard practice when it was found to prolong survival compared with conventional chemotherapy. There follows a list of the conventional drugs that we myeloma folks know well, from thalidomide to bortezomib. Dr. Rajkumar states that the results have been remarkable and that curing rather than controlling myeloma has become the goal of many specialists.

He adds, though, that it is not uncommon to find that well-meaning investigators interpret the same clinical trial data in opposite ways because they ascribe to different philosophies (cure vs control). Hmmm, so the same data can be interpreted in more than one way…this statement makes a good case for getting a second opinion, if not a third and fourth, before making any decision regarding treatment. Eh.

Then we get to the first important statement (from my point of view): It is far from clear whether increasing or intensifying therapy for patients without CR until such status is achieved actually prolongs overall survival. In other words, although the achievement of CR is a favorable prognostic factor, modifying therapeutic strategy with the sole purpose of achieving CR in a patient who is otherwise responding well to therapy is of unproven value. Precisely.

Dr. Rajkumar then makes a series of very good points, which you can go read for yourself. I will simply highlight a few:

  • in clinical trials, CR is often but not consistently associated with better overall survival.
  • trying to achieve the highest CR rate may cause harm […]. High CR rates frequently require more aggressive, more toxic therapy.
  • a small monoclonal protein (minimal residual disease) is not in itself clinically important and is commonly present in the general population in the form of monoclonal gammopathy of undetermined significance. In many patients, reduction of myeloma to a state similar to monoclonal gammopathy of undetermined significance (near-CR or very good partial response) may be all that is required for best long-term survival.
  • CR in myeloma, unlike CR in large cell lymphoma, reflects profound tumor reduction but not elimination of the clone and thus is not a true surrogate for cure.
  • achievement of a CR seems particularly important in the 15% of patients with high-risk myeloma, whereas survival is similar in patients without high-risk features who have and have not achieved CR.

A question popped into my head as I was reading this article: how many patients do poorly for the rest of their lives or die as a result of the harsh CR-type therapies compared to those who actually achieve CR? Dr. Rajkumar makes no mention of this…yet there must be statistics…

There follows a discussion on stem cell transplants, both autologous (using one’s own stem cells) or allogeneic (using a donor’s stem cells). Interesting.

I was curious to know Dr. Rajkumar’s personal opinion. Outside of a clinical trial setting, he prefers the more cautious approach, the “control” one…except in a few high-risk cases. He implies that this approach gives more decisional power to the patient (I am so glad to know that Dr. Rajkumar does not follow the “Dr. House” approach to treating patients! P.S. I watch “Dr. House” even though sometimes it makes my blood pressure soar…).

Well, I am with Dr. Rajkumar. My motto is “primum non nocere.” Since the more toxic approach is not curative…why subject your body and spirit to it? It just doesn’t make any sense, that is, unless your myeloma is aggressive, unless you are a high-risk patient, unless nothing else works…

And, while we are at it: why in the world would you choose to have chemotherapy if you are MGUS or stable SMM, without any CRAB symptoms? Does it make sense to get your myeloma cells all worked up and possibly more aggressive? Especially given that, and I repeat Dr. Rajkumar’s words (see above list), In many patients, reduction of myeloma to a state similar to monoclonal gammopathy of undetermined significance (near-CR or very good partial response) may be all that is required for best long-term survival. Indeed.

Unless we have a stubborn and aggressive type of myeloma, there are heaps of things we can do to delay or even stop (hey, why not shoot for the moon? 😉 ) the progression from inactive to active myeloma. I have suggested many scientifically-backed approaches right here. So have a few blog readers. Whatever works…

Just my opinion…as usual.


  1. I couldn’t agree with you more! We are of like minds on this issue, although I know several MMers who believe that the disease must be attacked aggressively. Sadly, I have seen several of them suffer life-altering side effects w/o amelioration of their disease. Everyone has to follow their own instincts, but I hope to hold off the most serious therapies until truly necessary!

  2. I shouldn’t have started treatment as soon as I did and shouldn’t have kept it up all based on my IgA results. I think they feared sludgy blood. I actually had no symptoms. I just felt a little tired and did catch every virus that blew through town. No anemia, no lesions. I suffered through 5 years of dex and everything else. Then SCT, which gave me 18 months of treatment free time so far. I’m taking curc now, and my box of other stuff just came from the “Acme” vitamin shop today. 🙂 No plugs here!

  3. Great post Margaret.

    I agree with you and Dr. Rajkumar. At a recent myeloma support group meeting, the speaker was a colleague of Dr. R. at Mayo. When they met at December’s ASH conference, he quoted Dr. R. as saying that for the first time in his career he felt hope for myeloma patients.

    Coupling that quote with his philosophy of care vs. cure makes me think that overall survival is on the upswing. Results from clinical trials with the latest novel agents and those following regimens including curcumin are unavailable as yet. Not enough time has passed.

    Doctors and clinics are not yet altering the old 3-5 year prognosis. But I believe that will change as time moves on and these options for “managing” myeloma improve outcomes.

  4. I couldn’t agree more!!! I believe quality of life is way more valuable than quanity. Expensive poisonous treatments seem only to benefit the medical industry. There is a video called Healing Cancer from the Inside Out that I recently viewed on Free Speech TV on sattelite- check it out or I think it can be bought but it sheds light on the monetary rich industry and how cancer is the biggest industry of them all. I personall have stopped participating in that insanity let go of my insurance and am improving my quality of life every day and I’m enjoying my life more.

  5. The docs have an interesting way interpreting “doing no harm” when it comes to cancer treatment.

    I believe they should pay more attention to “hasten to help”. We dealt with that (for Jaymun) last year – see

    If they are ignoring a complete subset of things they can do to “hasten to help” how can they properly decide how to not do harm?


  6. Some doctors are excited now about the 4-drug cocktails that can achieve a very high response rate and CR for many. But I wonder about the long-term effects of such intense treatment – does this approach extend survival, does it provide for high quality of life, how many patients get chemo-brain, or injuries to liver or kidneys?

    Does this approach preclude later, more-standard treatments? When I mentioned the 4-drug cocktail to my first onc, he said “you have only so many arrows in the quiver – would you want to shoot them all at once?” Dunno.

    Some doctors still encourage new patients to get a transplant early, rather than later, on the theory that the treatment-free period that may follow a transplant can best be enjoyed while the cancer is still in its early stages. But for me, a transplant will be the last resort, only for that time when nothing else will achieve stability.

  7. I wonder what the criteria is for distinguishing a “stubborn and aggressive cancer” and how that alters your physician’s treatment plan.

    I think it’s fair to say you can’t have a career in oncology unless you believe in your heart that the best possible outcome is possible for each and every patient. And yet… are you willing to be realistic when presented with a “stubborn cancer,” and make quality of life a priority over quantity? Accept that no treatment might provide a better (albeit short-term) result for that patient? I understand that this would be difficult for an oncologist, but it should be possible, shouldn’t it?

    I don’t know. I only have questions, not answers.

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