Is taking dexamethasone necessary as part of a myeloma treatment regimen?
Dexamethasone is in a class of drugs called steroids and is one of two commonly used steroids in multiple myeloma treatment (the other is prednisone). Dexamethasone is an important backbone of multiple myeloma treatment and is routinely used in combination with other multiple myeloma drugs for patients with newly diagnosed and relapsed/refractory myeloma. The reason dexamethasone is used is that it can directly kill multiple myeloma cells and when used in combination with a variety of agents patients can achieve high clinical response rates. Dexamethasone use is associated with many different side effects, some of which negatively impact a patient’s quality of life. The side effects caused by dexamethasone are a main reason why many patients ask about options for treatment that don’t include it. There have been many efforts in various clinical trials to exclude the use of dexamethasone, but for now, dexamethasone is still required as part of many treatment regimens.
What is the relationship between a mutation in the gene for TP53 and the deletion of chromosome 17 and are there any treatments for patients with these particular genetic abnormalities?
Many genetic changes occur in multiple myeloma cells and some of these changes may influence how aggressively myeloma cells grow or how responsive they may be to treatment. Using cells collected from a bone marrow biopsy, specific genetic tests are performed by myeloma doctors to detect genetic changes which helps to provide a full picture of a myeloma patient’s disease. Some tests only look at changes occurring at the level of the chromosome and others look at the changes occurring at the level of the specific genes that reside within an area of a chromosome. Which test is used will determine the different ways doctors will refer to the genetic changes. So, let’s first define changes at the chromosome level. All individuals have two pairs of 23 chromosomes (one set from his or her mother and father) and each are numbered. Each chromosome has a long arm—called q—and a short arm—called p. If a patient is said to have a deletion 17p (also shown in writing sometimes as del17p), that patient has a deletion (a part of the chromosome is missing) within the short arm of chromosome 17. At the gene level, there are many different genes that reside within that area of chromosome 17 and one such gene is called TP53. If a patient is said to have a TP53 mutation, that patient no longer has a normally functioning TP53 gene. The importance of having a normally functioning TP53 gene is that it can produce a protein called p53 which is a tumor suppressor protein, and as its name implies, the protein is a gatekeeper standing guard to make sure that cancer doesn’t develop. When the TP53 gene doesn’t function normally because of a mutation, the cell loses its ability to keep from becoming cancerous.
Deletion 17p and TP53 mutations are high risk genetic changes which means that patients who have these genetic changes do not do as well following treatment as those patients who do not. There are several clinical studies investigating ways to improve outcomes for high-risk patients in general, but there are no specific drugs available that will help a patient with this type of chromosomal or genetic abnormality.
More information on Genomics can be found in this HIT video.
How long after you’re diagnosed is an autologous stem cell transplant (ASCT) recommended?
The improved response rates seen in initial therapy with today’s myeloma regimens have raised questions about the timing of ASCT in the treatment of myeloma. A European study compared early ASCT (that is, ASCT performed right after induction) to late ASCT (performed after relapse) and showed that patients who got an early transplant tended to have a longer time without relapse than did those who got a late transplant. This result does not mean that all patients necessarily live longer after receiving an early transplant. For now, early ASCT (for suitable candidates) remains a standard therapy and may offer the best chance for a long-lasting response.
More information about the timing of an ASCT is addressed in a separate FAQ post here and in this HIT video.