Certain Chromosomal Abnormalities May Negatively Affect Prognosis In Relapsed And Refractory Myeloma Patients Receiving Revlimid-Dexamethasone Therapy
Results of a recent German study show that the chromosomal abnormalities del(17p13) and +1q21 may reduce overall survival in relapsed/refractory multiple myeloma patients receiving Revlimid-dexamethasone compared to patients without these abnormalities.
The results also indicate that patients with t(14;16) receiving Revlimid-dexamethasone have a shorter time to disease progression than patients without this abnormality. In addition, patients with del(13q14) in combination with certain other chromosomal abnormalities may have decreased response rates and a shorter time to disease progression.
The study authors, however, recommended additional evaluation of these chromosomal abnormalities in larger patient populations, since their study was small.
Chromosomal abnormalities, which result from the deletion, insertion, duplication, or movement of chromosomal segments, are considered high-risk factors for myeloma patients.
Certain abnormalities may affect patient response to specific therapies. For instance, a recent study showed that the chromosomal abnormalities del(1p21) or del(17p) decreased overall survival and time to disease progression for relapsed/refractory myeloma patients taking Revlimid (lenalidomide)-dexamethasone (Decadron) therapy (see related Beacon news).
However, according to the authors of the new study, there is currently little data available on how chromosomal abnormalities affect outcomes in patients who are being treated with the novel agents thalidomide (Thalomid), Revlimid, or Velcade (bortezomib). In addition, what findings there are have been relatively inconclusive.
In their study, the German researchers sought to further assess whether certain chromosomal abnormalities affect the outcome of Revlimid-dexamethasone therapy in myeloma patients who are relapsed or resistant to treatment.
They also investigated whether high-dose chemotherapy followed by autologous stem cell transplantation improved the outcome of relapsed/refractory myeloma patients with chromosomal abnormalities after receiving Revlimid-dexamethasone.
The researchers retrospectively analyzed the medical records of 92 relapsed/refractory myeloma patients with chromosomal abnormalities who had received a median of two prior therapies. The median age of the patients was 65 years. Bone marrow samples were taken prior to Revlimid-dexamethasone therpay, and the following chromosomal abnormalities were identified in the patients: +1q21, del(13q14), del(17p13), t(4;14), t(11;14), and t(14;16).
All patients received 25 mg Revlimid on days 1 to 21 and 20 mg dexamethasone on days 1 to 4, 9 to 12, and 17 to 20 of a 28-day treatment cycle until disease progression or unacceptable side effects developed.
After receiving Revlimid-dexamethasone therapy, 27 patients also received high-dose chemotherapy with 200 mg/m2 melphalan (Alkeran) followed by autologous stem cell transplantation.
The researchers observed a decreased response rate in patients with the chromosomal abnormality del(13q14). Patients with del(13q14) had an overall response rate of 50 percent compared to an 81 percent overall response rate for patients without del(13q14). These patients also had a briefer time to progression (5.1 months) than patients without del(13q14) (14.4 months).
The researchers found, however, that del(13q14) was linked to the abnormalities t(4;14) and del(17p13), and patients who had del(13q14) but neither of these two abnormalities did not experience a decreased response rate or time to progression.Patients with t(14;16) also had a briefer time to progression (2 months) than patients without t(14;16) (10.5 months).
Patients with del(17p13) or +1q21 had shorter overall survival times of 6.7 months and 8.3 months, respectively, compared to patients without these abnormalities, whose median overall survival was not yet reached at a median follow-up time of 12 months.
Because patients with t(4;14) as their sole chromosomal abnormality experienced similar results as patients without the abnormality, the researchers indicated that t(4;14) may not negatively affect the outcome of patients receiving Revlimid-dexamethasone.
They also found that after 12 months, patients who received high-dose chemotherapy followed by autologous stem cell transplant had a significantly higher overall survival (100 percent) compared to patients who did not receive these therapies (56.5 percent).
For more information, please see the full article in the journal Cancer (abstract).
Related Articles:
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Sustained Complete Response To Initial Treatment Associated With Substantial Survival Benefit In Multiple Myeloma
- Importance Of Factors Affecting Multiple Myeloma Survival Changes With Patient Age
- Nelfinavir-Velcade Combination Very Active In Advanced, Velcade-Resistant Multiple Myeloma
Dear Howard: I am a real fan of the Myeloma Beacon. Generally the news articles are timely and educational. Frequently, I can directly relate the findings to my MM. This article was an exception.
Most myeloma patients, myself included are elderly. When we went to school in the 50's and 60's molecular biology valiantly was in its infancy and the roles of DNA,RNA and proteins in cellular activities were just being potulated.
Since being diagnosed with MM I have attempted to learn the jargon of my disease with only partial success. Molecular biology is one of my stumbling blocks.The Myeloma Beacon news articles generally help me wade through the name jungle. But this time you confronted me with terms such as del(17p13),del(13q14),+1q21 and more. How about a little help in the education department with the p's and q's. At least give me a simplified reference (e.g. Idiots guide to....) where I can learn what you, and the authors, are trying to say.
Remember there are bunch of golden oldies out here who really want and need to know what is going on but we we don't speak your language. Gary
P.S. If other patients have learning aids that would help me master molecular biology please send them along.
I am somewha perplexed. Are these chromosomal deficits only present in patients who have received the chemo or are they present in MM prior to Rx with chemo? Are the deficits caused by the chemo?
Thank you, Gary and Nancy, for your feedback and questions regarding this article.
Regarding your question, Nancy, the chromosomal abnormalities that typically are discussed in research articles like this one are not abnormalities caused by any of the myeloma treatments being discussed. They are a natural aspect of the disease itself. They do vary, however, from patient to patient, and, as was mentioned in this article, they tend to affect a patient's prognosis and how the patient responds to certain treatments.
That said, it's not clear when the patients in this study had their chromosomal abnormalities determined. Were they determined prior to the treatments discussed in this article? At diagnosis? Or some other time? We will look into this and get back to you with further information.
Regarding your feedback, Gary ... When we were preparing this article, we debated how much background information to include in it. In the end, we felt there were so many different abnormalities mentioned in the article that it would really bog things down to describe each abnormality in detail.
More than likely, for each abnormality, we would have had to have included a description like "The t(11;14) abnormality, or 'translocation-11-14', occurs when chromosomal material has been exchanged between chromosomes 11 and 14."
That would have been a lot of extra text!
Your commment, though, makes me wonder if we need to revisit the issue. We'll discuss tomorrow when we're all back at the office after the holiday today here in the States.
Thanks again!
For those looking to better understand chromosomal abnormalities:
Each person's genetic material (DNA) is stored in chromosomes. Humans normally have two copies of 22 different chromosomes as well as two sex chromosomes (XX for women and XY for men). Each chromosome has two regions, a short region (p) and a long region (q), and specific positions on the chromosome are numbered. Therefore, 17p13 would refer to position 13 of the short region of chromosome 17.
There are a number of different types of chromosomal abnormalities. The ones related to myeloma are not typically present at birth; they occur at some point during life either due to errors that occur when chromosomes are copied during cell division or due to environmental factors that cause chromosomal damage. The most common chromosomal abnormalities related to myeloma, and those described in this article, include:
Deletion – A part of a chromosome is missing. For example: del(17p13) would mean that on chromosome 17, position 13 of the short arm is missing.
Translocation - A portion of one chromosome is transferred to another chromosome, or two chromosomes swap portions. For example: t(4;14) means that chromosomes 4 and 14 have swapped some of their genetic material.
Gain - There is an extra copy of a chromosome or part of a chromosome. For example: +1q21 would mean that this person has an extra copy of position 21 of the long region of chromosome 1.
Dear Nancy,
We followed up with the study authors to find out when the patients were tested for chromosomal abnormalities. The lead author, Dr. Kai Neben, told us that the bone marrow samples were taken at different time points, but in the majority of the cases, prior to Revlimid-dexamethasone therapy, which means that the therapy did not cause the chromosomal abnormalities.
Thanks Myeloma Beacon for an outstanding explanation of chromosomal abnormalities technical terms!!
It is difficult at times as Gary said even if some molecular biology is known since the shorthand terms are not really associative. For instance, who would associate p with short? Or q with long region when it comes to descriptors? I mean how come they didn't simply use s for short and l for long? Just a rhetorical question as I know it has all been settled.
Perhaps, the p stands for something in addition to short?
OTOH, t for translocation makes a lot of sense and is easily memorable. lol
Just curious.
Again thanks for the excellent detailed explanation!!!
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