An important result of this study is the significant difference between treatment outcomes depending on the biological subgroup, as defined by FISH, into which the patient falls. Consistent with previous work, we have defined adverse FISH as gain 1q , del 17p , t 4;14 , t 14;16 and t 14;20 , and favorable FISH as the remainder; in addition we have incorporated del 1p32 as a high-risk factor in younger patients. Furthermore, we show that, in the group with favorable interphase FISH, there was a trend for improvement in OS for patients receiving thalidomide induction, where there were no effects for those with adverse cytogenetics.
These results suggest that the group benefiting from the introduction of thalidomide into the induction therapy of younger patients with NDMM is defined by favorable biological characteristics, identified by their FISH subgroup.
Altogether, these findings underscore the need for the incorporation of FISH analysis into the assessment of patients for entry into trials and for the routine management of these patients. Although the induction regimens evaluated in this study were associated with similar rates of adverse events, the spectrum of events differed. Compared with CVAD, CTD was associated with a higher incidence of severe constipation and somnolence, which is consistent with the known toxicity profile of thalidomide.
Notably, the CTD regimen was associated with less myelosuppression than CVAD and this may have contributed to the reduction in fatal cases of infection, facilitated stem-cell collection, and reduced hospital admissions.
In subgroup analyses, a significant survival benefit was observed in patients who achieved a CR and had favorable interphase FISH. Based on these results and comparing an oral to infusional regimen with significant negative impacts on patient lifestyle, which has a substantial risk of myelopsuppression, CTD offers an effective alternative induction regimen associated with improved response rates that is not inferior to CVAD and may have additional benefits in favorable biological subgroups.
The authors would like to thank all the patients, investigators, and staff at the participating centers who made this study possible. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Gareth J. Morgan Faith E. Davies Walter M. Gregory Sue E. Bell Alexander J. Johnson Claudius Rudin Mark T.
Drayson Roger G. Owen Fiona M. Ross Nigel H. Russell Graham H. Jackson J. Anthony Child. Abstract Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation.
Design and Methods Oral cyclophosphamide, thalidomide, and dexamethasone was compared with infusional cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. The complete response rates were Cyclophosphamide-thalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with cyclophosphamide-thalidomide-dexamethasone in responders.
A trend toward an overall survival advantage for cyclophosphamide-thalidomide-dexamethasone over cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with cyclophosphamide-vincristine-doxorubicin-dexamethasone, cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. Conclusions The cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior in terms of survival outcomes to the standard infusional regimen of cyclophosphamide-vincristine-doxorubicin-dexamethasone.
Based on its oral administration and the reduced incidence of infection and cytopenia, cyclophosphamide-thalidomide-dexa-methasone may be considered an effective induction therapy option for patients with newly diagnosed multiple myeloma. Patients Eligible patients were aged 18 years or more and had symptomatic MM. Treatments Patients were assigned to either an intensive or non-intensive treatment pathway 19 based on performance status, clinician judgment, and patient preference.
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Google Scholar. Blood 15 : Connected Content. This is a related article to: Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Cite Icon Cite. Conflict-of-interest disclosure: The author declares no competing financial interests. Search ADS. Thalidomide-dexamethasone compared to melphalan-prednisolone in elderly patients with multiple myeloma.
Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. A randomized trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma E4A03 : A trial coordinated by the Eastern Cooperative Oncology Group: analysis of response, survival and outcome [abstract].
Melphalan-prednisone-thalidomide to newly diagnosed patients with multiple myeloma: a placebo controlled randomized phase 3 trial [abstract]. Oral melphalan, prednisone and thalidomide in elderly multiple myeloma patients: Updated results of a randomized controlled trial. Add comment Close comment form modal. Submit a comment. Comment title.
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Download references. You can also search for this author in PubMed Google Scholar. Correspondence to Elena Zamagni. Reprints and Permissions. Zamagni, E. Long-term results of thalidomide and dexamethasone thal—dex as therapy of first relapse in multiple myeloma. Ann Hematol 91, — Download citation.
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