Myeloma patients under age 50 – Margaret's Corner

Well, so much for giving up research for a few days.

But last night Sherlock sent me a new “Blood” study that perked my interest. You can read the abstract here: http://tinyurl.com/264753 And, as usual, I would be happy to forward the full study to anybody upon request.

A few preliminary remarks:

1. I am always wary of statistics, of which this study is full. Lots of numbers! My head was spinning at one point…

2. The study considers only myeloma patients undergoing conventional treatments.

3. Specifically: “Patients with smouldering (asymptomatic) myeloma, amyloidosis and monoclonal IgM disorders were not included.”

That said, the study contains some interesting information. As follows.

The International Myeloma Working Group analysed 10,549 myeloma patients for this project. 17 institutions and study groups from North America, Japan and Europe participated in the study, which covers the period 1981-2002. Most of the patients were from Europe.

The authors “report the presenting features and outcome after conventional and high-dose therapy in 10,549 myeloma patients and compare the findings obtained in 1,689 patients less than 50 years of age with those of 8,860 older patients.” 70% of all the patients had participated in clinical trials (7,413 people). Stage of the disease was assessed using the International Staging System, or ISS (see: http://tinyurl.com/2ab8sw), and the Durie-Salmon system, see: http://tinyurl.com/ytcqe9

“Median age of all 10,549 patients combined was 60 years.” 1,689, or 16%, were younger than 50 years of age. Most of these were between 40 and 50. Only 312 were younger than 40, and 27 younger than 30.

Younger patients had fewer adverse prognostic factors such as low albumin and high B2M (beta-2 microglobulin). They also scored better than older patients in terms of haemoglobin, C-reactive protein and creatinine. The two groups (a. more than 50 years of age, b. less than 50) had comparable levels of LDH and bone marrow plasma cell infiltration, which indicated “an absence of a major difference in the biology of the myeloma clone between young and older patients.”

Interesting bit of information about the <40 group: most of the patients, 67%, were male. The authors speculate further on that it could be due to “increased androgenic sex hormone levels in young males.” No difference, however, between male and female patients.

Risk of death was higher in the older patients. Now, excuse me for pointing out the obvious, but had the reverse had been found, i.e. that younger patients died at a higher rate than older ones, that would have made no sense, right? So the following bit of news hardly seems to be earth-shattering: “Better outcome in the younger cohort was seen in all three ISS stages and was independent of gender.”

In particular, “High-dose chemotherapy with autologous stem cell transplantation resulted in a higher relative excess risk of death in the older patients (median survival 5.7 years) compared to the younger patients (7.5 years). Similarly, the observed 10-year survival rate was significantly higher in the younger patients (43% versus 29%, logrank P=.005). Relative survival was similar in the subgroup of patients aged 40 to <50 years versus that of very young patients, both after conventional chemotherapy (4.4 years versus 4.7 years) and after autologous transplantation (7.3 years versus 7.5 years) (relative excess risk estimate: 1.09 and 0.93, respectively). And 10-year survival rates were also similar, both after conventional (21% versus 19%, P=.37) and after high-dose treatment (44% versus 38%, P=.76, by log-rank test).”

Sorry about all these long quotes, but it’s difficult to summarize numbers!

Ah, and what have we here? Another long quote! As follows: “Conventional therapy was given to 994 (58.9%) of the 1,689 patients aged less than 50 years and to 6,771 (76.4%) of the older patients, while high-dose therapy was administered to 695 (41.1%) of the younger and to 2,089 (23.6%) of the older patients, respectively. The percentage of young patients enrolled during different time periods for treatment with conventional therapy decreased from 94.2% in the period between 1981-1987 to 21.3% in the years between 1999-2002 (P<.001) while the proportion of those subjected to high-dose therapy increased from 5.7% to 78.7% (P<.001)(Table 3). The respective figures for older patients were 98.8% to 40.1% (P<.001) for conventional, and 1.2% to 59.9% (P<.001) for high-dose therapy.”

And now we get to the final part of the study (I skipped a lot of the numbers, eh!), and, you guessed it, here is another long quote: “The most important finding in this study on 10,549 patients with multiple myeloma was the significant differences in the presenting features between young and older patients. Young patients presented with significantly lower ISS stage and consequently had less frequently elevation of ß2-microglobulin and reduction of low serum albumin levels. In addition, significantly fewer younger patients presented with poor performance status, anemia, renal impairment, or increased CRP levels. Older patients, in contrast had a greater prevalence of less favorable prognostic factors. Hence, both a lower ISS stage at diagnosis and overall better prognostic factors seem to account for the superior survival in young patients treated with high-dose therapy after correction for differences in life expectancies, with age remaining an independent risk factor for patients treated with conventional therapy.” Another finding was the low number of young patients: only 0,26% were younger than 30 years of age. Young age was associated with longer survival.

The study concludes that “myeloma patients less than 50 years of age had significantly longer age-adjusted survival both after conventional and high-dose therapy (5.4 and 7.5 years, respectively) in relation to older patients (3.7 and 5.7 years, respectively). Given the fact that thalidomide and other new drugs were not available for the great majority of patients, the 10-year survival rate was remarkably high in young patients after conventional (19%) and high-dose therapy (43%). The major factors accounting for this improved outcome of young patients were presentation with a lower ISS stage at diagnosis and other more favorable prognostic features.”

Even though, as stated above, I am wary of statistics and take them with a grain of salt, I admit that I would really like to read a similar statistical analysis concerning those of us following alternative treatments. Perhaps some day…who knows?

2 Comments

Dear Margaret,
I don’t understand why the article says that patients with smouldering myeloma were not included, when Stage I of MM is exactly SMM and the authors give data on patients at Stage I of MM. Am I wrong?

Sherlock

I took a second look at the study, and Stage I refers not to the Salmon-Durie classification system but to the more recent International Staging System or ISS. I presume that these patients had some CRAB involvement. It is also true that some haematologists favour early intervention (which is not a good idea, as we know from the literature).
Margaret

2 Comments

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