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Understanding Prognosis In Multiple Myeloma

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Published: Mar 1, 2012 1:29 pm

One of the most difficult questions in oncology is: “How long do I have to live?”

Patients often bring this up to their physicians following a diagnosis of cancer, and periodically during the course of their disease.

Of course, this is an impossible question to answer because we as physicians can seldom predict what the future holds for a particular patient. We can prob­a­bly estimate averages, but no patient is average; everyone is unique. Faced with this dilemma, each physician responds differently. Some provide the averages, some don’t.

Nevertheless, it is incredibly difficult for all.  Patients are entitled to have some idea of prognosis, but at the same time physicians feel unqualified to provide estimates that they themselves do not understand.

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News articles about:
- prognosis and survival

Forum discussions about:

- prognosis and survival

Also, be sure to see the Beacon’s August 2013 up­date on mul­ti­ple mye­lo­ma sur­vival and the Sep­tem­ber 2013 update on multiple my­e­lo­ma risk cat­e­go­ries.

This already perplexing problem is made even worse in multiple myeloma be­cause overall survival outcomes vary considerably based on so many dif­fer­ent variables referred to as prognostic factors. Understanding these fac­tors is crit­i­cal not just for physicians wanting to counsel patients and choose the right ther­a­py, but also for patients who often hear about these “risk fac­tors” or “high-risk markers” from other patients, the Internet, and so on.

First, it is important to recognize that overall survival for an individual patient with myeloma is determined not just by markers of aggressive disease biology (e.g., high-risk chromosomal abnormalities) but also by host factors (e.g., age and overall health) and the extent of myeloma (stage).

Second, each of these factors affects survival differently, and each needs to be tackled differently.

The strategy to overcome high-risk chromosomal abnormalities differs from strategies to overcome the problems posed by advanced age, other health problems, or kidney failure. Even within the overall group of high-risk chromosomal abnormalities, certain abnormalities may need to be tackled in a slightly different manner than others.

So there is no easy, uniform way to overcome “high risk.” It will depend on what exactly the high risk-factor is, and what can be done about that particular factor.

Third, things change over time. For example, response to therapy (good or bad) can have a dramatic effect on outcome and disrupt prior survival calculations. Similarly, patients may acquire new chromosomal abnormalities that change the dynamics of the disease and its treatment.

With the above understanding, we can now discuss what options are available to tackle each risk factor.

Host factors are typically approached by modifying treatment intensity.

Thus, in patients with advanced age, we avoid stem cell transplantation and often reduce the dose and intensity of chemotherapy to minimize toxic side effects and maximize control of the myeloma.

For patients with kidney failure, we try methods such as plasma exchange and chemotherapy with drugs that act rapidly to try and quickly reverse the kidney damage.

Disease stage is less important in myeloma than in other cancers for choosing therapy. However, treat­ments in myeloma can be modified in select situations based on disease stage.

For example, in patients with stage I multiple myeloma by the Durie-Salmon staging system who have a single bone lesion, radiation alone may be adequate, while systemic treatment is needed for more ad­vanced stages.

Disease biology is indeed one of the most important determinants of outcome. Among patients with similar age, overall health, and disease stage, survival can vary widely based on markers of aggressive disease biology.

At present, we consider deletion 17p, translocations t(14;16), t(14;20), a high-risk gene expression profiling signature, a high lactate dehydrogenase level, and plasma cell leukemia as high-risk factors.

Yet not all patients with these markers have high-risk myeloma.

For example, a recent study led by my colleague Dr. Shaji Kumar shows that the presence of trisomies (an extra copy of one or more chromosomes) can neutralize the high-risk effects of certain high-risk factors (i.e., t(14;16), t(14;20), and 17p).

Similarly, translocation t(4;14) was previously considered to be a high-risk factor, but recent research sug­gests that Velcade (bortezomib)-based induction, stem cell transplantation, and Velcade-based consolidation/maintenance may be effective against this risk factor.

What are the treatment options for high-risk myeloma? There is intense research ongoing to improve sur­viv­al in this patient population.

Depending on the patient’s age and other health problems, treatment options vary – but many are available. Most researchers believe that the best strategy overall in high-risk myeloma is to try and achieve a complete response, or as close to one as possible, and then try to sustain it.

While it is important to provide some data to patients with high-risk myeloma to answer questions about prognosis, it is also important to note that no marker is perfect. We all have patients with 17p deletion who have done very well for many, many years and who defy textbook predictions.

Finally, while we make treatment plans based on the risk factor groups discussed above (host factors, stage, high-risk disease markers), they can change based on response to such therapy.

Progressive myeloma while on therapy is usually a sign that we need to change the treatment plans and regimens. However, response to therapy is complex and is affected by numerous factors.

Suffice it to say that while an excellent response to therapy is always desirable, we cannot get carried away with numbers alone. For example, there are patients who respond very slowly to therapy and never reach a complete response, but yet they achieve some of the best survival figures.

It is more important to recognize that the interplay between response and outcome is complex, and there is no need to grieve over failure to achieve a complete response.

I know this column probably raises more questions than it answers. My goal is to highlight that estimating and understanding prognosis is no easy task.

I believe that well-informed myeloma patients can work with their physicians to get a full picture of their own unique situation and to plan the most appropriate treatment strategy.

Dr. S. Vincent Rajkumar is a professor of medicine at the Mayo Clinic in Rochester, Minnesota. His research focuses on clinical, epidemiological, and laboratory research for myeloma and related disorders.

Photo of Dr. S. Vincent Rajkumar, professor at the Mayo Clinic.
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15 Comments »

  • David Keegan said:

    Excellent article. The end result I gather is, there is no crystal ball. The varibles are so vast, that a prediction is impossible. One key factor that i did not see mentioned was the “mental” health of the patient. A postive outlook tends to increase ones ability to fight the progression of the myeloma. I learned very early, not to believe everything I read on the internet. If I had, I’d be dead already, instead of 13 months in complete remission.

    “Life is not waiting for the storm to pass, it is learning to dance in the rain”

  • nancy shamanna said:

    Hi Dr. Rajkumar…just wanted to relate that we bought your book ‘Treatment of Multiple Myeloma and Related Disorders’ (2009 – Cambridge University Press) – Edited by yourself and Robert Kyle. It has been helpful to us to try to get an understanding of MM. Where would we patients all be today without the dedication of researchers and oncologists such as yourself? The book is a comprehensive overview of MM, amyloidosis, and other related diseases.

    I enjoy your articles in the Beacon…thanks for your helpful insights.

  • Dan D said:

    Thanks for your opinion, which (to me) underscores the unpredictable, multi-factorial, and individualized nature of this disease.

    I would like to know under what conditions — if any — you would recommend an upfront/immediate stem cell transplant to low-risk, early-stage, younger patients. (I am not in need of treatment yet — but may begin soon).

    Also, I am curious to hear of exceptional cases of long-term survival. For example, have you seen (or do you know of) patients who have been around for more than 20 years post-diagnosis? And if so, are there any attributes of such patients that you have gleaned.

  • Gary Petersen said:

    Dr. Rajkumar, an excellent article on the complexity of this disease, and the need to find a specialist with your remarkable myeloma skill set to ensure a positive long term prognosis. Because of this expertise, I could only expect that your patient survival statistics could also be remarkable.

  • Jan Stafl MD said:

    Thank you for the best review of multiple myeloma prognosis variability that I have read! As a gynecologic physician and MM patient, I have now experienced the cancer survival question from both sides. It has helped me appreciate the difficulty in estimating and communicating prognosis as a clinician, as well as the need to have some idea of survival range by the patient. More than most cancers, MM has so many variables that make prognosis estimation quite formidable, as you so eloquently express.
    In addition to age and overall health, several other host factors are of upmost importance, and I feel need to be discussed. The mental and emotional status of the patient, as well as the social support he or she has, does affect immunity through complex interactions known as psychoneuroimmunology. That has been confirmed through thousands of studies. More controversial, but likely just as important, is the spiritual connectedness of an individual. I suspect that it does not matter what faith or belief an individual has, but some connection to a higher power (or meaning of life) is important.
    Western medicine does not deal with these prognostic variables very well, if at all. Nor does it recognize the existence of energy fields (Chi, prana, bioenergy, etc.) in and around the body, as most other healing modalities do. My personal view is that Holistic Medicine, which integrates body, mind and spirit, results in the best outcome for not just various cancers, but most chronic conditions. Surgery, chemotherapy, radiation and immunotherapy all have crucial roles, but without attention to the mental, emotional and spiritual aspects of any dis-ease and the individual with it, the outcome will be suboptimal. Even when a cure is not possible, deep healing can and does occur!
    So thank you again for an excellent article. I just wanted to offer a holistic viewpoint on this important subject.

  • Lori Puente said:

    Well, look on the bright side… at least we have moved away from the one size fits all 3-5 year scenario no matter what your presentation.

  • Suzanne Gay said:

    so it’s again “we don’t know, we don’t know, we don’t know….” well, isn’t that Life in general? Go with the flow.

  • Bob Kirkpatrick said:

    My diagnosis placed me at advanced stage 3 and both my oncologist and the physician who was solicited for a second opinion gave me a six month prognosis. Those two opinions were underscored by yet a third oncologist who offered a concurring opinion. That awful news was given to me in February of 2008. The emotional damage of those prognosis’ is indescribable and were a primary reason for my considering a death with dignity.

    I applaud your column! I wish more doctors could be at ease with the answer “I don’t know,” rather than inflict yet another complication to an already unfortunate situation. I think it’s perfectly alright for physicians to offer the general statistics, but with the disclaimer that each case is, as you say, different.

    Thank you for your post.

  • David A. said:

    It’s refreshing to discuss delicate life and death matters with genuine frankness yet with comforting compassion. I have been searching for an answer to this question and I wish someone out there can help.

    My significant other has been suffering with Multiple Myeoloma for years now. Been through induction treatment, three autologous transplants and is now doing chemo. She is going on 8yrs survival. My suspicion is that the vivelle dot(HRT) she is using is responsible for the disease. I’ve tried to convince her to quit but to no avail. I have not found a research that firmly ties HRT to Multiple Myeloma but I have seen incomplete studies that have certain hints but nothing definite. I strongly believe that her condition will be vastly improved if not permanently but appreciably if I can find evidence to show that the vivelle dot is a culprit. Is there any knowledge that can be shared? Cytogenic lab shows t(11,14)t(13,32), trisomies 11, 17.

    She is being treated now with Treanda (Bendamustine) for CCL that just got worse in a very short time. She still is taking the vivelle dot. I’m confounded.

  • nancy shamanna said:

    Hi David A. … your question would be a really good one for the physicians on site here! I see that the Vivelle dot is an estradiol patch used to alleviate symptoms of menopause. The warnings associated with it include not using it if you have or have had cancers of the breast or uterus, since they can be fuelled by estrogen.
    Menopause can be very difficult, but usually it only goes on for three or four years, or at least that is my experience. Best wishes to your partner and you!

  • Jan Stafl MD said:

    To David A: I appreciate your concern for your female friend with MM, who has been through multiple treatments. As a gynecologist, I prescribe Vivelle dot (a bioidentical transdermal estradiol patch) to many menopausal women, usually with bioidentical progesterone. The lowest therapeutically efficacious dose is prescribed when menopausal symptoms persist despite dietary and lifestyle changes, and/or when herbal therapy (such as black cohosh) do not help. I suspect that the main benefit of this natural HRT for many women is mental and emotional. It should be gradually weaned off if possible after about five years though.
    Multiple Myeloma is not an estrogen sensitive cancer; in fact, men are at higher risk than women. Low dose estrogen (with or without progesterone) is not known to increase any cancers in the general population when used less than five years, and actually protects women from colon cancer! With Multiple Myeloma, it is difficult to identity a specific cause, although some data implicates benzene exposure and other environmental chemicals. Most of us with MM however cannot point to any specific cause. So it is not why, why, why, as much what we can do about it.
    I hope that helps. Best wishes to you and your friend, who is evidently quite courageous!

  • Chitaranjan K V said:

    Fantastic and simple presentation.As an old class mate and buddy I am really proud of you, Hats off to Dr. Vincent chitaranjank@gmail.com

  • joeypalooka said:

    Thank you for your great articles and comments, but im so confused about my prognosses i cant even think straight. with my luck i wont last too long !!!

    Joeypalooka

  • suzierose said:

    Hi Joey!

    You will last long!! Just start asking questions about the prognosis. You might want to post in the forum section, where folks will contribute and assist you in any way that is helpful.

  • Moni said:

    Dear Dr.Rajkumar,

    I read in one of the websites that turmeric is found to be effective in the treatment of Multiple myeloma. I would like to know more about it. Is there a way I can get in touch with you? Or at least can I get more info?

    -Moni