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Do β2 microglobulin levels affect survival of newly diagnosed myeloma patients with translocation t(4;14) or 17p13 deletion treated with conventional chemotherapy?

Leukemia volume 22, pages 1080–1081 (2008)Cite this article

Recently, the Intergroupe Francophone du Mye'lome (IFM) published their data on the impact of genetics on survival in a large cohort of newly diagnosed patients treated with high-dose melphalan and stem cell transplantation (HDT). They showed that t(4;14) and 17p13 deletion are powerful independent prognostic factors in patients with either of these abnormalities identifying a group of patients with the worst prognosis. However, among these patients, those with β2 microglobulin (B2M) >4 mg l−1 have significantly shorter survival (median survival of about 20 months).1 B2M level of >4 was also an independent prognostic factor among 100 patients with t(4;14) treated with tandem stem cell transplantation on IFM trials.2

In contrast to the IFM experience, our analysis in a sizable cohort of patients with long-term follow-up suggests that B2M levels do not add prognostic value to high-risk genetic factors. The median survival of our patients with t(4;14) and/or 17p13 deletion and B2M levels >4 mg l−1 is 24 months, similar to the survival of 20 months for the same cohort of patients in the IFM study. The major difference between the two studies is the longer survival of patients with t(4;14) and/or 17p13 deletion with low B2M in the IFM trials (median 40 months versus 26 months). This difference may be due to the difference in upfront therapy in the two studies: HDT compared to melphalan-based chemotherapy. Alternatively, changes in the spectrum and effectiveness of post-relapse salvage therapies may explain the difference. The ECOG study was conducted in a time when salvage therapies are limited. In contrast, the IFM studies are conducted after the year 2000, in the era of effective salvage agents such as thalidomide, lenalidomide and bortezomib. As PFS directly measures the effect of primary therapy, the lack of effect of B2M level on PFS in the Mayo cohort, while significantly affecting PFS in the IFM studies, suggests that the difference in upfront treatment between the two cohorts may be the main contributory factor to the difference in the impact of B2M on survival in the two cohorts. Therefore, our observations suggest that HDT may benefit patients with high-risk cytogenetics with low B2M. Our analysis, therefore, adds evidence that the prognostic impact of various factors is modulated by therapy. Accordingly, existing and new prognostic factors have to be re-evaluated in the context of emerging therapies.

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References

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  1. Mayo Clinic, Comprehensive Cancer Center, Scottsdale, AZ, USA

    W J Chng & R Fonseca

  2. Eastern Cooperative Oncology Group Statistical Center, Dana Faber Cancer Institute, Boston, MA, USA

    S Jacobus

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  1. W J Chng
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  2. S Jacobus
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Correspondence to R Fonseca.

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Chng, W., Jacobus, S. & Fonseca, R. Do β2 microglobulin levels affect survival of newly diagnosed myeloma patients with translocation t(4;14) or 17p13 deletion treated with conventional chemotherapy?. Leukemia 22, 1080–1081 (2008). https://doi.org/10.1038/sj.leu.2405009

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