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).
