Interesting article on secondary primary malignancies in myeloma. One thing I thought was interesting, the authors did not seem to think the high dose melphalan used prior to auto was much of a factor in developing secondary MDS/AML. They indicated it had more to do with how extensive Induction was prior to the high dose melphalan.
"Given the historical experience with melphalan-associated t-MDS/AML, concern arose over the risk in myeloma patients treated with high-dose melphalan. Govindarajan et al. reviewed 188 pts with myeloma who underwent HDT/SCT at the University of Arkansas [22]. In 117 patients who received extended courses of chemotherapy prior to tandem autotransplantation, 7 cases of MDS were seen, whereas in 71 patients who received limited chemotherapy prior to transplantation, no cases of MDS were seen. They concluded that preceding therapy was likely the cause of MDS in most cases seen after HDT/SCT, a finding that mirrored conclusions from studies in Hodgkin lymphoma (HL) [23].
The Arkansas experience was reviewed again over a decade later, this time including 3077 patients undergoing HDT/SCT for myeloma, most of whom were treated on their total therapy or total therapy-like protocols [24]. MDS-associated cytogenetic abnormalities were seen in 6%, although in roughly 2/3 of these cases, the karyotypic changes were only transient. The risk of clinically overt MDS/AML was even less, estimated at only 1% of transplanted patients. Survival after the diagnosis of t-MDS/AML in transplanted patients has been poor in most studies with a median of about 6 months [20]."
Interesting discussion on Revlimid (lenalidomide) as well.
"A truly satisfactory explanation would require a better understanding of how lenalidomide works in patients with hematologic malignancies, let alone myeloma. This is an area of active research, but certainly more needs to be done. Unlike traditional cytotoxic chemotherapies, lenalidomide showed no mutagenic potential in extensive genotoxicity studies performed during its development [27]. And although carcinogenicity testing was not performed, chronic studies in rat and monkey revealed no potential for tumorigenicity. However, lenalidomide is clearly myelosuppressive and tumoricidal, and after a prolonged exposure may affect the ability to mobilize and collect stem cells. Perhaps these properties are an indication of a myelotoxicity which may predispose to MDS or AML. One could also speculate that lenalidomide’s immunomodulatory properties and its effects on the tumor microenvironment may allow for the propagation of abnormal clones which can result in a malignancy. The complex mechanisms of action responsible for lenalidomide’s activity, as well its unclear molecular target, make it difficult to rely on preclinical data to assess the safety and neoplastic potential of lenalidomide."
http://www.hindawi.com/journals/ah/2012/801495/
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