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Cytogenetics in Multiple Myeloma: the Value of Individualized Care

Value-Based Care in Myeloma - Cytogenetic Testing, Multiple Myeloma
Gary M. Owens, MD
President
Gary Owens Associates
Glen Mills, PA

The management of multiple myeloma (MM) has evolved rapidly over the past decade, due in large part to the addition of thalidomide, lenalidomide, and bortezomib to the treatment paradigm for the disease. Myeloma is currently staged using the International Staging System (ISS), which utilizes 2 laboratory parameters (paraproteins and albumin) to determine prognosis.1 According to this staging system, the median survival times for patients with stage I, II, and III disease are 62, 44, and 29 months, respectively. 2 It has become increasingly evident, however, that MM is a disease with cytogenetic, molecular, and proliferative heterogeneity, and these differences can affect outcomes. For example, retrospective analyses of clinical trials have shown that therapeutic responses among patients with MM can vary substantially, based on parameters beyond those measured by the ISS.3 Therefore, alternative staging systems have now become available, such as mSMART (Mayo Stratification for Myeloma and Risk-adapted Therapy) consensus guidelines, which include an evidence-based algorithm for making treatment decisions in newly diagnosed MM.4,5

Through the use of conventional cytogenetic testing and fluorescence in situ hybridization (FISH), we now know that the analysis of myeloma cells is of prognostic value. For example, deletion of chromosome 13, nonhyperdiploidy, and the balanced translocations t(4;14) and t(14;16) are unfavorable prognostic factors for patients with MM treated with either conventional or high-dose therapy.6,7 Conversely, 11q13 and 6p21 cytogenetic abnormalities are associated with a somewhat favorable prognosis.8 In the future, additional diagnostics, such as high-density, single-nucleotide polymorphism (SNP) array karyotyping, which can detect copy number alterations of prognostic significance that may be missed by a targeted FISH panel, may be used to further risk-stratify patients for treatment.9

The accompanying article provides an overview of chromosomal abnormalities in MM and their prognostic significance, along with a review of recent clinical findings regarding the efficacy of novel biologic agents in the context of high-risk cytogenetics. The article concludes by stating that long-term follow-up and validation of these findings will be necessary to truly assess the value of cytogenetics in the decision- making process in MM, and from a managed care viewpoint, I cannot agree more.

The cost of managing MM has escalated significantly and it is not uncommon for antimyeloma drugs to be among the top categories of therapies by total spending.10 Managed care organizations (MCOs) and prescription drug managers are being questioned by their customers about the cost of novel agents and their impact on outcomes. Although we can definitively say that the use of novel therapies has significantly improved response and prolonged survival, myeloma remains an incurable disease. Furthermore, the choice of treatments for MM has expanded significantly over the past several years. Currently, clinicians individualize therapy based on disease stage, as well as the patient’s comorbidities and eligibility for transplantation. Ultimately, having additional criteria based on cytogenetic and FISH testing, SNP array karyotyping, and other markers will enable clinicians to better target therapy to their patients and select the most clinically beneficial and cost-effective regimens. As MCOs, we need to encourage the pursuit of such investigations. Of course, a major question that remains is “Who will fund this research?” Now is the time for stakeholders to open the dialogue with their colleagues and discuss critical issues such as the design and funding of clinical trials, and how outcomes can be used for both the provision and payment of care. It is only through such joint efforts that we will ultimately take steps toward true value-based treatments for MM that will provide the maximum clinical benefit in a cost-effective manner.

References

  1. Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412-3420.
  2. Raab MS, Podar K, Breitkreutz I, et al. Multiple myeloma. Lancet. 2009; 374:324-339.
  3. Fonseca R, Stewart AK. Targeted therapeutics for multiple myeloma: the arrival of a risk-stratified approach. Mol Cancer Ther. 2007;6:802-810.
  4. mSMART criteria. http://msmart.org/newly%20diagnosed%20myeloma. pdf. Accessed February 25, 2011.
  5. Kumar SK, Mikhael JR, Buadi FK, et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART) consensus guidelines. Mayo Clin Proc. 2009;84:1095-1110.
  6. Fonseca R, Barlogie B, Bataille R, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res. 2004;64:1546-1558.
  7. Dewald GW, Therneau T, Larson D, et al. Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma. Blood. 2005;106:3553-3558.
  8. Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood. 2007;109:3489-3495.
  9. Avet-Loiseau H, Li C, Magrangeas F, et al. Prognostic significance of copynumber alterations in multiple myeloma. J Clin Oncol. 2009;27:4585-4590.
  10. Cook R. An economic perspective on treatment options in multiple myeloma. Managed Care Oncol. 2007;3:10-12.
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Last modified: May 20, 2015
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