Findings from a recent retrospective study conducted by researchers at the Mayo Clinic show that overall survival for multiple myeloma patients treated at that cancer center has improved significantly between 2001 and 2010.

Patients diag­nosed between 2001 and 2005 had a median overall survival of 4.6 years, while those diag­nosed more recently – be­tween 2006 and 2010 – had an improved median overall survival of 6.1 years, or almost one-third higher.

In addition, the share of patients dying within a year of diagnosis, known as early mor­tal­i­ty, also decreased significantly during the 10-year time period, from 16 percent to 10 percent.

The results show, however, that only patients diag­nosed after the age of 65 years experienced significantly improved survival.  The median overall survival for this age group increased from 3.2 years for those diag­nosed between 2001 and 2005 to 5 years for those diag­nosed between 2006 and 2010.

The researchers attribute the survival improvement among older patients to the increased use of novel drugs – such as Revlimid (lenalidomide) and Velcade (bortezomib) – and stem cell transplantation in this age group.  They also note that, in the earlier time period, the survival of younger patients had already benefited from the use of novel agents, and that the lack of further improvement in survival among younger patients highlights the need for more innovative treat­ment approaches.

The Mayo study's age-related findings appear on the surface to con­tra­dict those of a study published earlier this year.  The earlier study showed that, over the last decade, older mye­lo­ma patients throughout the United States have not benefited as much in terms of survival as younger pa­tients (see related Beacon news).  These findings were based on data from the National Cancer In­sti­tute’s Sur­veil­lance, Epidemiology, and End Results (SEER) database, which is a key source of U.S. cancer statistics.

Dr. Dianne Pulte from Thomas Jefferson University, the lead investigator of the earlier SEER-based study, explained that the differences in the findings from the two studies are likely due to one being based on data from patients treated at the Mayo Clinic, a single research institution, while the other is based on data from the general population.

“Doctors in the community, especially those not specializing specifically in myeloma, may not be as aware of advances in the treatment of myeloma, particularly for older patients, as doctors at the Mayo Clinic,” explained Dr. Pulte.  “Thus, improvements in survival may occur sooner at the Mayo Clinic than in the general population.”

“I would speculate that we may see a greater improvement in survival for older patients in the general population in the years 2011 to 2015, as advances pioneered in the Mayo Clinic and similar institutions become routine in the community,” Dr. Pulte continued to explain.  “Conversely, there may not have been a significant increase in survival [among younger patients] between 2001-2005 and 2006-2010 at the Mayo Clinic because the changes that led to better survival in that period in the general community had already occurred at the Mayo Clinic by 2001 to 2005.”

Dr. Shaji Kumar, lead investigator of the current Mayo Clinic study, also pointed out that the SEER-based study included earlier time points (1998 to 2009) than the Mayo Clinic study (2001 to 2010).

Background

While multiple myeloma remains a largely incurable disease, studies have shown that sur­viv­al for myeloma patients has improved significantly over the last few decades. Improvements in sur­viv­al occurred in the 1990s due to the wider use of stem cell transplantation, and continued in the 2000s with the introduction of novel anti-myeloma agents.

However, according to the authors of the current study, it is not clear whether sur­viv­al has in­creased as dramatically over the last few years, particularly in older patients.

The researchers therefore sought to assess changes in the sur­viv­al of multiple myeloma patients in the recent decade.

Study Design

The researchers analyzed the records of 1,038 newly diag­nosed multiple myeloma patients who started treatment at the Mayo Clinic between 2001 and 2010.

The patients were separated into two groups based on the year that they started treatment: 2001 to 2005 (477 patients), and 2006 to 2010 (561 patients).

Patients in both groups were similar in terms of age (median 66 years) and risk factors such as disease stage and chromosomal abnormalities.

The median follow-up time was 5.9 years.

Results

Survival Rates

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The median overall survival for all of the patients in the study was 5.2 years.

However, the median overall survival significantly increased from the first half of the study to the second half, with the median overall survival being 4.6 years for patients diag­nosed between 2001 and 2005 and 6.1 years for those diag­nosed between 2006 and 2010. (See overall survival graph on the right.)

The same trend was seen in the six-year overall survival rate.  Across all patients in the study, 45 percent of the patients survived six years.  Among those diag­nosed between 2001 and 2005, the six-year survival rate was 40 percent; the rate increased to 51 percent for those diag­nosed be­tween 2006 and 2010.

The researchers also showed that there was a steady improvement in survival over the 10-year span of the study.

Age

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Click on image to view a larger version of it.

When the researchers looked at survival based on age, they found that patients who were 65 years and younger did not experience any im­provement in survival during the study period.  (See top overall survival graph on the right.)

However, patients older than 65 years, both those above 65 years to 75 years, as well as those above 75 years, experienced improved survival (median of 3.2 years in the 2001 to 2005 group of over-65-year-olds, com­pared to 5 years for the same patients in the 2006 to 2010 group). (See lower overall survival graph on the right.)

Use Of Novel Agents

Next, the investigators assessed changes in the use of novel drugs and stem cell transplants between the two time periods.

The investigators found that a significantly greater share of patients in the latter group had received novel agents as part of their initial therapy com­pared to patients in the earlier group (29 per­cent in the earlier group versus 89 per­cent in the latter group).

Furthermore, novel agent use significantly im­proved overall survival (median 3.8 years for those who did not receive a novel agent as part of their initial therapy, com­pared to not yet reached for those who did).

The researchers found that when novel agent use and year of diagnosis were considered, only novel agent use was associated with improved survival.  This finding indicates that improved survival in recent years is mostly related to increased use of novel agents.

Use Of Stem Cell Transplantation

Among all patients included in the study, 37 percent underwent autologous stem cell transplantation (using their own stem cells) at some point in the treatment of their disease. Stem cell transplantation significantly improved overall survival (median not yet reached for those who underwent transplantation com­pared to 4.9 years for who those who did not).

Among patients less than 65 years of age, however, stem cell transplantation did not impact median overall survival (median overall survival not yet reached for both those who did and those who did not undergo transplantation).

However,  patients older than 65 years who underwent stem cell transplantation had significantly longer median overall survival (not yet reached) than those who did not (3.1 years).

The researchers explain that older myeloma patients must have good overall health in order to be eligible for stem cell transplantation.  Therefore, the finding that older patients who undergo transplantation have better survival reflects their better health com­pared to other older myeloma patients (as well as the efficacy and safety of transplantation for older patients).

Prognostic Factors

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The researchers also examined how the impact of prognostic factors, such as the International Stag­ing System (ISS) and chromosomal ab­nor­mal­i­ties, has changed over the last decade.

Overall survival appeared to increase from the first half of the study to the second half for all three ISS stages.  (See graph on the right for overall survival by ISS stage for patients diag­nosed in the 2006-2010 time period.)

For ISS Stage 3 multiple myeloma (31 percent of patients), median overall survival increased from 2.1 years for patients diag­nosed between 2001 and 2005 to 4.2 years for patients diag­nosed between 2006 and 2010.

For ISS Stage 2 myeloma (39 percent of patients), median overall survival increased from 5.7 years to not yet reached.

For ISS Stage 1 multiple myeloma (30 percent of patients), overall survival was not yet reached for both time periods, but appeared to be greater for those diag­nosed during the latter half of the study.

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Similarly, median overall survival for the 12 percent of patients with high-risk chromo­somal ab­nor­mal­i­ties – such as t(4;14), t(14;16), t(16;20), or del17p – increased from the earlier time period (2.4 years) to the latter time period studied (5.1 years). (See graph on the right for over­all sur­vi­val by risk classification for patients diag­nosed in the 2006-2010 time period.)

Early Mortality Rates

Over the entire course of the study, 13 percent of the patients died within the first year of diagnosis. However, the one-year mortality rate significantly decreased during the study, from 16 percent for patients diag­nosed between 2001 and 2005, to 10 percent for patients diag­nosed between 2006 and 2010.

Patients who received one or more novel agents as part of their initial therapy had lower early mortality com­pared to those who did not (8 percent versus 19 percent, respectively).

Among patients treated with novel agents, which are now the standard of care, the researchers identified several factors that were associated with early mortality. These included age greater than 70 years, low albumin levels in the blood (less than 3.5 mg/dL), and high beta-2 microglobulin levels in the blood (greater than 6.5 mg/dL).

Patients with all three of the identified factors were at the highest risk of early mortality (53 percent) com­pared to those with two (9 percent), one (5 percent), or none (3 percent).

For more information, please refer to this study in the journal Leukemia (abstract).