Treatment effects and the role of autologous stem cell transplantation

I recently returned from the American Society of Hematology meeting in New Orleans – more on that later, in both column and print form, in the days and weeks ahead. I was reflecting this morning on a patient I recently saw in clinic, in light of one of the plenary presentations at the meeting.

Many of you may be aware of the plenary presentation that attempted to answer questions about the appropriate anti-myeloma partner for bortezomib and the role of maintenance therapy in multiple myeloma. In the study, patients newly diagnosed with multiple myeloma were randomized one of four treatment arms. The increase in complete remission from induction through maintenance was substantial (from about 20% to about 40%) and the OS and PFS for both groups at two years was significant. In both groups, the usual adverse prognostic features of cytogenetic abnormalities at diagnosis appeared to be overcome by the use of bortezomib containing treatment strategies. The differences between the thalidomide vs. melphalan groups did not appear particularly substantial.

Now, back to my patient. This was a man who presented with modest renal dysfunction, plasmacytomas, a monoclonal protein spike on SPEP, and markedly abnormal serum free light chains. He had been treated by his local oncologist with a lenalidomide, bortezomib and dexamethasone regimen, with excellent disease response. When he saw me after four cycles of therapy, his light chain ratio and SPEP were entirely normal. Unfortunately, he was significantly disabled by the treatment, and his QOL was nonexistent. He had fatigue, profound neuropathy, steroid-related hyperglycemia (diabetic) and generalized muscle wasting.

I thought again about the plenary presentation. I need to look closer at the data, but in looking at the abstract again it seemed that the dropout rate from diagnosis to three years of maintenance was fairly substantial (it seemed that about 60% of patients initially assigned completed maintenance therapy). So, a treatment strategy of induction followed by extended maintenance therapy with new anti-myeloma drugs may make sense for patients who don’t have significant treatment-related side effects, but for others this may be difficult to tolerate.

In my mind, this is where autologous stem cell transplantation may make a lot of sense. Offering certain patients, post-transplant, the opportunity for an extended progression-free, potentially treatment-free, period of time. In the end, this was the rationale we outlined to the patient I saw in clinic and this is the route that he chose. Extended bortezomib maintenance may be a great idea in the right circumstances, but it may not be for everyone.