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Spanish Experts Ask: What Is The Path To A Cure For Myeloma?

By: Howard Chang; Published: December 9, 2011 @ 9:19 am | Comments Disabled

In a recent editorial published in the journal Haematologica, two Spanish myeloma experts, Dr. Jesús San-Miguel and Dr. Maria-Victoria Mateos from the University Hospital of Salamanca, review the progress that has been made in the treatment of multiple myeloma.

More importantly, Drs. San-Miguel and Mateos propose several actions they believe will bring the medical community closer to a cure for myeloma.

These actions include achieving and maintaining the best possible response early in the treatment of the disease, using advanced tools to evaluate and optimize treatment efficacy, and seeking an appropriate balance between efficacy and toxicity of treatment.

Some Historical Perspective

In their editorial, the authors point out that multiple myeloma had been considered an incurable disease for decades before the introduction of more advanced treatment options such as stem cell transplantation and novel agents. The goal of treatment during this earlier period was simply to control the spread of the disease as much as possible so that patients could survive for up to two or three years.

The authors go on to explain that the introduction of high-dose therapy followed by autologous stem cell transplantation produced several important results. It prolonged survival by an average of one year, increased the complete response rate to between 15 percent and 30 percent, and made it possible for myeloma patients to enjoy a good quality of life for longer periods of time.

Treatment outcomes improved significantly in the last decade with the advent of the novel agents thalidomide [1] (Thalomid), Velcade [2] (bortezomib), and Revlimid [3] (lenalidomide). The use of novel agents has helped double the survival of myeloma patients compared to two decades ago when only chemotherapy was used.

Cure ... Or Control?

According to the Drs. Mateos and San-Miguel, these recent advances in myeloma treatment have brought the possibility of a cure in sight more than ever before. They therefore raise the question: Should the goal of myeloma treatment be “cure” or “disease control”?

The authors comment that even disease control - which many would consider to be treatment that allows a patient to survive for over 20 years with a good quality of life - is still far from becoming a reality. Today, the authors write, median survival is four to six years for elderly myeloma patients and eight to ten years for young myeloma patients.

Yet, during the years when a myeloma patient's disease is "under control," he or she still must deal with the uncertainty and anxiety that happens every time a relapse occurs.  This is why disease control, from the authors' perspective, is a less desirable goal than a true cure.

In the opinion of the authors, for physicians to be able to say to patients that multiple myeloma is a potentially curable disease, treatment options must advance to the point where at least 40 percent to 50 percent of patients are staying in complete remission for more than ten years after treatment.

Currently, only 3 percent to 10 percent of myeloma patients remain in complete remission for more than ten years after receiving an autologous stem cell transplant, according to Drs. San-Miguel and Mateos.  Although patients may achieve better survival outcomes with a donor (allogeneic) stem cell transplant, this procedure entails a high rate of transplant-related mortality and may not be feasible for the majority of patients.

Three Steps Toward A Cure

In order to work towards the goal of a cure, the editorial authors propose three actions that should be emphasized when treating myeloma patients.

First, the authors propose that treatment should focus on destroying all cancer cells in the body.

Past studies have shown that the deeper a patient’s response to therapy, the longer the patient will survive. In order words, destroying all cancer cells implies ensuring that the patient achieves and maintains the best possible response to therapy.

“In most [blood] disorders [such as myeloma], there is an axiom: If you want to cure the patient, you should use the best possible treatment upfront in order to reduce the tumor as much as possible, and to completely eliminate the tumor cells including the cancer stem cells,” Dr. San-Miguel explained to The Beacon.

“This axiom implies [that we should try to] achieve the best possible response. I do not mean that this needs to be achieved with two or three cycles [of therapy], but that we should use an optimal treatment upfront,” he added.

The authors acknowledge, however, that certain myeloma patients may survive for a long time even without achieving a complete remission. Instead, these patients revert to a disease state similar to monoclonal gammopathy of undetermined significance (MGUS), a myeloma precursor disease in which patients experience none of the symptoms associated with multiple myeloma (see related Beacon [4] news).

Second, the authors propose using appropriate tools to evaluate treatment efficacy.

For instance, advanced imaging techniques enable physicians to determine the level of residual cancer cells in the body after treatment, thus making it possible to prevent under-treatment or over-treatment.  In addition, genetic studies at diagnosis enable physicians to identify high-risk patients who may be resistant to certain therapies.

Third, Drs. Mateos and San-Miguel recommend seeking a balance between efficacy and toxicity of treatment by taking into account the patient’s quality of life, prolongation of survival, and the possibility of a cure.

One way of doing this, of course, is to bear in mind patient age and health.

For instance, the authors believe that the treatment goal for healthy, elderly patients between 65 years and 70 years of age should be both to prolong survival and to ensure a good quality of life.

On the other hand, the treatment goal for very elderly patients over 85 years of age should be to ensure a good quality of life while avoiding unnecessarily expensive treatments (that place undue pressure on already overburdened health care budgets).

In patients under 65 years of age, the treatment goal should be to find and use a regimen that can potentially cure the disease.

“The number of years of life lost by young patients with multiple myeloma is four to five times more than that of elderly patients. For this reason, the most aggressive treatment should be first explored in young patients. Also, [young patients] are usually more fit to receive intensive therapies,” commented Dr. San-Miguel.

“By contrast, in elderly patients, it is most important to preserve a good quality of life,” he added.

Lower Toxicity Or Longer Survival?

In closing, the editorial authors state that, in searching for a cure, researchers should not focus on therapies that may reduce toxicity, but not prolong survival in myeloma patients.

Many myeloma specialists advocate a so-called risk-adapted approach to therapy, in which patients with lower-risk disease are treated less aggressively than patients with higher-risk disease (see related Beacon [5] physician column).  Drs. San-Miguel and Mateos do not completely reject this approach, but they are not very sympathetic to it.

Instead, they believe working towards a cure requires a focus on prolonging survival and finding new therapies and more effective combinations and sequences of existing therapies.

“The way to find a cure for myeloma is a continuous interaction between defining genetic variants of myeloma, discovering novel drugs, and including patients in well-designed Phase 2 and Phase 3 clinical trials. Only joint efforts and interactions in these three areas will lead us to rapid improvements in our results,” commented Dr. San-Miguel.

“Myeloma is a very heterogeneous disease and I think in the coming years we will learn that some drugs that are very active in some genetic or phenotypic variants do not work in others. This will lead to a more "personalized" treatment approach,” he added.

For more information, please see the article in the journal Haematologica [6].

Article printed from The Myeloma Beacon: http://www.myelomabeacon.com

URL to article: http://www.myelomabeacon.com/news/2011/12/09/spanish-experts-ask-what-is-the-path-to-a-cure-for-multiple-myeloma/

URLs in this post:

[1] thalidomide: http://www.myelomabeacon.com/resources/2008/10/15/thalidomide/

[2] Velcade: http://www.myelomabeacon.com/resources/2008/10/15/velcade

[3] Revlimid: http://www.myelomabeacon.com/resources/2008/10/15/revlimid/

[4] Beacon: http://www.myelomabeacon.com/news/2009/03/04/blood-disorder-mgus-precedes-most-cases-of-multiple-myeloma/

[5] Beacon: http://www.myelomabeacon.com/news/2010/12/03/risk-adapted-therapy-for-multiple-myeloma-by-dr-vincent-rajkumar/

[6] Haematologica: http://www.haematologica.org/content/96/9/1246.long

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