Practical Approaches in Myeloma: Optimal Management of Newly Diagnosed and Relapsed/Refractory Disease.
I met a woman Friday whose myeloma was diagnosed in 2008, and who was told by two different Washington D.C. hematologists that she should get her affairs in order because she didn't have long to live. Both of those doctors were wrong - she is very alive and doing much better today, thank you, because she learned better online and found doctors who know more than those two. The American Society of Hematology (ASH) Conference began Friday night with a "Satellite Session" presented by the International Myeloma Foundation (IMF), designed to help doctors understand diagnosis and treatment of myeloma at all stages. It was a primer aimed at the practitioner who needs a refresher course in "what's current." Four different doctors gave presentations, with Dr. Durie of the IMF acting as chair. A doctor who attended that session would not make the mistakes that the two D.C. doctors made.
Dr. Vicent Rajkumar of Mayo Clinic in Rochester spoke first about diagnosis, explaining the comparative benefits of immunofixation, serum protein electrophoresis, and free light chain analysis. We need all three because myeloma is not a single disease, and can sometimes hide from any one of them but not from all. Further, we may need both FISH and cytogenetic studies to examine the particular risk factors for any particular patient.
He mentioned that people with monoclonal gammopathy of undetermined significance (MGUS) have a 1% per year probability of progressing to myeloma, whereas those with smoldering myeloma have a 10% probability of progressing to symptomatic myeloma each year. He also thinks that neuropathy may be treated as another "C.R.A.B." (calcium, renal, anemia, bone) symptom that can herald the onset of Stage I myeloma, particularly when the neuropathy cannot be attributed to any cause other than the myeloma.
Dr. Phillippe Moreau, of Nantes, France, described current and new treatments for newly-diagnosed patients, including many different combinations of drugs. The audience, mostly hematologists, was asked whether autologous stem-cell transplant (ASCT) was the "standard of care" for newly diagnosed patients, and 75% said yes. Dr. Moreau's studies in Europe, however, seem to be showing that combinations of new drugs can do as well at achieving "Very Good partial Responses" (VGPR) or Complete Responses (CR), and that those responses do hold up to provide time-to-progression and overall survival comparable with transplants. For high-risk patients, however, the data is not available and ASCT may be the safest choice.
If a transplant is contemplated, it appears to be beneficial to use the drug combinations first anyway, because achievement of VGPR or CR before the transplant improves the outcome of the transplant. The question was asked, "if a patient preparing for a transplant achieves a CR, do we go ahead with the transplant anyway?" The doctors at the speakers' table did not agree on the answer to that question. If my opinion counts for anything, I personally would never embark on a transplant having already achieved CR or even VGPR. Go on maintenance and save the transplant in case it's really needed some day.
One of Dr. Moreau's studies has shown that a reduced Velcade regimen with a reduced dexamethasone (DEX) regimen can be effective but with much less neuropathy.
Consolidation is used after a major treatment such as a transplant. It is an additional drug regimen designed to improve the transplant outcome and bring the patient to a CR or at least VGPR.
Maintenance is used after a transplant or other major treatment, to maintain the good result achieved there. It DOES improve the overall survival. According to Dr. Moreau, that question is answered.
In answer to a question from the audience, Dr. Rajkumar said that there is no data showing that an early transplant improves a person's survival compared with a later transplant. This question is under study though.
Dr. Mario Boccadoro of Turin, Italy, described the treatment options for patients aged 65 and beyond, in Europe. In the USA we do not make a hard cutoff at age 65, but Europe does. He mentioned melphalan a lot, an "alkylating agents" which works by messing up the cell's DNA and perhaps initiating other cancers that will appear years later. Most of the regimens that he mentioned for us older folks have been around for years. He did mention one study that included Revlimid with the melphalan and DEX, and preliminary results looked good.
OF COURSE it looked good! And why shouldn't we ancients get the benefit of the novel therapies, just as the younger set does? Duh.
One interesting remark by Dr Boccadoro: In one of the studies, the control group had a better overall survival than the study group, despite the clear benefits of the study regimen. The explanation was that the patients in the control group were free to change regimens and do whatever was necessary to survive, whereas, apparently, the study group was not. I think I'll do my very best to opt OUT of a study like that.
He also spoke well of carfilzomib, the new proteasome inhibitor, under study at M. D. Anderson. It causes much less neuropathy than does Velcade, and is even effective for 30% of the patients who are refractory to Velcade. He also mentioned two more drugs, presently approved, which do not have specific anti-myeloma activity by themselves but which can improve the efficacy of another drug, such as Velcade.