Amsterdam, The Netherlands
Catching up with my reading, I recently noticed the article “Myeloma: Stem Cell Transplant Up Front or After Progression?” in the 12/25/08 issue. That debate involved Stage II-III patients. However, since 20% of patients present with Stage I, the question arises how to handle these patients.
I recently talked with a multiple myeloma patient of 42 years who had been diagnosed with Stage I multiple myeloma five years ago. She mentioned that exposure to environmental radiation was the possible cause of disease. At the time of diagnosis a donor search had been performed and two donors were and are still available. It had been decided to treat her with drug therapy and she had been kept five years on a variety of the newer drugs. She said that her disease had become chronic and that there was now a trend towards development of Stage II disease. She felt fine and was normally active and at work.
She questioned, though, whether she would still be curable after five years of drug treatment, concerned that the disease would have become resistant to chemotherapy. Moreover she questioned which moment would be the best to be transplanted in the current situation.
Stage I multiple myeloma is more or less asymptomatic and often not treated; treatment does delay the time to progression but has no impact on survival; five-years survival is 70%.
Allogeneic bone marrow transplantation is the only treatment option that indeed can cure the disease. A reduced intensity conditioning allogeneic transplant as part of therapy administered upfront in experienced hands has low risks.
A multiple myeloma patient diagnosed with Stage I disease, who desires curative therapy should be treated according to the gold standard: rapid remission induction, double consolidation of response, eradication of the disease preferably in first molecular remission.
In 2006 we described a strategy of a stepwise approach to assess the remission status (Blood 2006;108; abst 5355). In Stage I myeloma this approach could be followed upfront, whereby the newer drugs replace the dose-dense chemotherapy. However, it needs to be considered that dose dense chemotherapy might be just as well as newer drugs in multiple myeloma, only it has never been administered, as most patients were of older age at diagnosis, and myeloma has for years been undertreated.
In view of the questions of this particular patient, she would right away be a candidate for an autologous-allogeneic transplant strategy but has to accept the risk that there is s higher risk of treatment by transplantation than there was five years ago.
Finally it remains to be said that after having been in the ether for nine years, there has really been no progress in the education of most physicians that cure means to administer curative therapy from initial diagnosis. With the advent of more expensive newer drugs, integration of upfront tandem reduced-intensity conditioning autologous and allogeneic peripheral blood progenitor cell transplants is most curative and cost-efficient on long term.
Studies are warranted and investigators are invited to contact us.
MARLIES VAN HOEF, MD, PhD, MBA
Amsterdam, The Netherlands