Study Evaluates Autologous Transplant for Rare Myelomas

Abstract & Commentary

By Andrew S. Artz, MD, Hematology/Immunology Unit, National Institute on Aging, NIH. Dr. Artz reports no relationships relevant to this field of study.

Synopsis: Very limited data are available on autologous transplant outcomes for uncommon or rare multiple myeloma (MM) subtypes. The authors evaluated the European Group for Blood and Marrow Transplantation Myeloma Database comprising outcomes for the following subtypes: 379 IgD, 13 IgE, 72 IgM, and 976 non-secretory. Compared to more than 20,000 common myelomas, such as IgG, IgA, or Bence Jones Protein MM, IgD manifested inferior overall survival. IgE and IgM also fared poorly, but small numbers limited statistical comparisons. Non-secretory MM demonstrated similar OS to typical MM. Although survival of IgD, IgE, and IgM MM is worse after autologous transplant than typical MM, survival is reasonable compared to the poor outcomes previously reported. Novel approaches with maintenance are of particular interest for rare myelomas to improve outcomes.

Source: Morris C, et al. Efficacy and outcome of autologous transplant for rare myelomas. Haematologica. 2010; 95:2126-2133.

Over 90% of multiple myeloma (mm) patients will have either an IgG, IgA, or Bence-Jones Protein only. IgD and non-secretory MM are less common, whereas IgM and IgE are rare. Overall survival for non-secretory MM is thought to be similar to typical MM, whereas outcomes for IgD MM are poor.1,2 IgE and IgM are thought to fare poorly, although cases are rare. Autologous stem-cell rescue after high-dose chemotherapy remains an important tool in the treatment of MM.3 Limited data are available addressing outcomes after high-dose therapy and autologous transplantation for less common, or rare, MM subtypes.

The authors reviewed autologous transplant from the European Group for Blood and Marrow Transplantation, the primary transplant registry for Europe. Among the 22,244 transplants between 1986 and 2007, there were 976 non-secretory (4.4%), 379 IgD (1.7%), 72 IgM (0.3%), and 13 IgE (0.1%). The vast majority of transplants for MM were for IgG, IgA, and Bence-Jones Protein, for whom the median survival was 62.3 months. In comparison, IgD MM survival was shorter at 43.5 months (p = 0.0001), despite having high complete remissions, implying a higher relapse rate. Transplant-related mortality also was increased. Overall survival for IgM at 44.7 months mirrored outcomes for IgD MM. IgE showed the lowest median survival at 34 months, although the small size of both IgM and IgE limited statistical conclusions. Non-secretory MM showed significantly improved progression-free survival, but the median overall survival of 64.6 months did not differ from the 62.3 months for common myelomas.

Commentary

Autologous transplantation remains a mainstay for adequately fit MM patients based on randomized trials demonstrating improved survival. As expected, data are primarily derived from common ideotypes of MM: IgG, IgA, and those with Bence-Jones Proteins. To assess outcomes after autologous transplant for less-common myelomas, the authors evaluated the European transplant registry, contrasting infrequent myelomas of non-secretory, IgD, IgE, and IgM to the more common variants. Non-secretory myelomas showed better progression-free survival and similar overall survival to typical MM. However, the authors accurately point out the lack of sensitive paraprotein measures in non-secretory cases (the cohort was primarily before light chain assays) to assess response delays, formally declaring progressive disease and may exclude such patients from clinical trials. We can now more confidently counsel patients with non-secretory MM applying the reported clinical trial data for MM.

The worse survival for IgD, IgE, and IgM MM compared to typical MM is the most novel finding. The small numbers for IgM and particularly IgE limit reliable statistical comparisons, whereas the reduction in survival by approximately 19 months for IgD was clinically and statistically significant. The more germane question of whether autologous transplant is beneficial vs. conventional treatment cannot be answered in this study. As an observational study, the data clearly have limitations related to selection bias as those undergoing transplant are typically younger and/or healthier.

However, as these rare myelomas generally exhibit poorer overall survival than observed in this study and transplant benefits more common myeloma subtypes, it is reasonable to maintain transplant in the overall therapeutic strategy. Clearly, the introduction of novel agents such as bortezomib and thalidomide has remarkably altered the therapeutic landscape. Rather than excluding the need for transplant, the addition of novel agents for maintenance therapy after transplant has provided preliminary but highly promising results. The poor outcomes for rare myelomas emphasize the need in future studies to determine if reduced progression from maintenance therapy will extend to non-secretory and rare myelomas.

In conclusion, high-dose therapy followed by autologous transplant results in similar survival for non-secretory MM compared to the common ideotypes of IgG, IgA, and Bence-Jones Protein. The rare IgG, IgE, and IgM myelomas fare worse relative to common myeloma but best historical non-transplant outcomes. Thus, autologous transplant should still be entertained for less common myelomas, just as in the more common forms.

References

1. Kumar S, et al. Comparable outcomes in nonsecretory and secretory multiple myeloma after autologous stem cell transplantation. Biol Blood Marrow Transplant. 2008;14:1134-1140.

2. Blade J, et al. Immunoglobulin D multiple myeloma: Presenting features, response to therapy, and survival in a series of 53 cases. J Clin Oncol. 1994;12:2398-2404.

3. Child JA, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003;348:1875-1883.