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Making progress in treating multiple myeloma with total therapies: issue of complete remission and more

Leukemia volume 22, pages 1633–1636 (2008)Cite this article

A Corrigendum to this article was published on 13 August 2008

We appreciated Dr Bergsagel's thoughtful editorial1 accompanying our paper on the long-term survival of patients in whom metaphase cytogenetic abnormalities were effectively suppressed.2 We wish to put that work in the context of almost 20 years of clinical trial and translational research in multiple myeloma at the University of Arkansas for Medical Sciences.

When we introduced stem cell-supported high-dose melphalan as a therapeutic strategy for myeloma in the 1980s, we had employed stringently defined complete remission (CR, immunofixation negativity and absence of aneuploidy or cytoplasmic light chain restriction on flow cytometry) as an early trial objective and surrogate for event-free and overall survival extension.3 The younger readership needs to be reminded that in those days bone marrow examinations were not routinely performed at diagnosis let alone for re-staging, as all care was strictly palliative in nature. After decades of clinical trial research involving permutations of the melphalan–prednisone (MP) regimen,4 we demonstrated that high-dose dexamethasone in VAD (vincristine, adriamycin, dexamethasone) was an effective salvage regimen in MP-refractory myeloma.5 VAD was devoid of hematopoietic stem cell toxicity and thus afforded subsequent collection of autologous bone marrow and soon thereafter peripheral blood stem cells, which were associated with accelerated engraftment and a higher safety margin than bone marrow-derived support, especially in the elderly.6 As a melphalan dose of 200 mg m−2 was the maximum tolerated dose at which significant mucositis occurred, we decided to apply two cycles of melphalan at 200 mg m−2 initially 3–6 months apart in an effort to increase the net antitumor effect, an approach that became known as a ‘tandem transplant’. The objective was achieved in that the CR rate was increased from previously 20 to the 40% range, which was associated with prolongation of survival as reported in Total Therapy (TT) 1, the first such trial for newly diagnosed patients employing repeated cycles of stem cell-supported high-dose melphalan.7 Based on these results, we reasoned that a substantial fraction of patients had to have marked antitumor effect for a substantive proportion of patients to derive long-term benefit. Indeed, recent follow-up analysis of the TT1 trial revealed that among the 231 patients enrolled 54 are alive and 27 are event free, including 14 of the original 87 who entered stringently defined CR (s-CR) and whom we consider cured after 10–16 years of follow-up8 (update as of 1 January 2008).

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Acknowledgements

This work was supported by a program project grant from the National Institutes of Health (CA55819). We thank our medical support staff for their tireless efforts. We appreciate the trust and confidence of our patients and their referring physicians.

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Authors and Affiliations

  1. Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    B Barlogie, F van Rhee, J D Shaughnessy Jr & E Anaissie

  2. Cancer Research and Biostatistics, Seattle, WA, USA

    J Crowley

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Correspondence to B Barlogie.

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Barlogie, B., van Rhee, F., Shaughnessy, J. et al. Making progress in treating multiple myeloma with total therapies: issue of complete remission and more. Leukemia 22, 1633–1636 (2008). https://doi.org/10.1038/leu.2008.40

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