Our good friend and nutritional columnist, Danny Parker, is excited about a new study released last week in the Journal of the American Society of Hematology: Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma.
Danny is considered a high risk patient, so I understand why this comprehensive study might be of special interest to him and other patients with chromosomal abnormalities that might make treating their multiple myeloma more challenging.
Much of the study is devoted to reviewing different classifications of high risk cytogenetics. A useful undertaking, but the international researchers
- P. Leif Bergsagel1,
- María-Victoria Mateos2,
- Norma C. Gutierrez2,
- S. Vincent Rajkumar3,
- Jesús F. San Miguel2
don’t stop there. Listen to what they had to say at the end of their abstract:
Reviewing available data in high-risk MM from this perspective, it appears that bortezomib has frequently been associated with improved survival, whereas thalidomide maintenance has sometimes been associated with a shorter survival.
I would like to the email I received from Danny yesterday afternoon about the study. I think he does a great job summing things up:
This just came out and I believe significant. Mayo Clinic and Salamanca, Spain.
Shows a key result quantified that has been bandied about for years. Now, shown to be true.
Velcade (borezomib) related treatment at least partially overcomes hi-risk designation for myeloma. Thalidomide did not and the word on Revlimid (lenalidomide) is still out. Why is Velcade so helpful?
“We can only speculate as to the mechanism underlying these important clinical observations. The action of bortezomib is probably multifactorial, including targeting proliferation, ER stress, the unfolded protein response, and activating mutations of the NF-κB pathway.60,6162“ Targeting some or all of these may play an important role in the ability of bortezomib to abrogate the early mortality seen in high-risk MM. Furthermore, given that high-risk MM has recently been associated with increased genomic instability and clonal heterogeneity, it is probable that the deeper and faster responses seen with the addition of bortezomib may be particularly important.”
Moreover, the authors see evidence that low-dose Thalidomide in the maintenance setting may actually be a bad thing in hi-risk patients. In this context, the following conclusion is also worth repeating:
“… In contrast, the use of chronic, suboptimal doses of thalidomide as maintenance in such patients may more quickly lead to the selection of resistant clones, compared with thalidomide use at full doses in the relapsed setting.”
Below: Red is Bortezomid based regimens; green are Thalidomide based ones with comparison of 3 year OS vs. non-hi-risk group.
For those of you unfamiliar with international studies of this type, thalidomide is the IMiD of choice, because Revlimid’s use is still tightly controlled in most of Europe, restricted to specific classes of relapsed/refractory patients, similar to the way the FDA approved pomalidomide (POMALYST) a week ago Friday.
I will post a brief beginner’s primer tomorrow that should be quite helpful to newly diagnosed myeloma patients, their families and caregivers.
Until then, feel good and keep smiling! Pat