Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma

Lokhorst, Henk M.; Schmidt-Wolf, I.; Sonneveld, Pieter; Holt, Bronno van der; Martin, Hans; Barge, Renée M. Y.; Bertsch, Uta; Schlenzka, Jana; Bos, Gerard M.J.; Croockewit, Sandra; Zweegman, Sonja; Breitkreutz, Iris; Joosten, Peter; Scheid, Christof; Marwijk-Kooy, Marinus van; Salwender, Han-Juergen; Oers, M. H. van; Schaafsma, Ron; Naumann, Ralph; Sinnige, Harm; Blau, Igor Wolfgang; Delforge, Michel; Weerdt, Okke de; Wijermans, Pierre W.; Wittebol, Shulamit; Duersen, U.; Vellenga, Edo; Goldschmidt, Hartmut

doi:10.3324/haematol.11644

Cited by 135 publications

(83 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[74][75][76] With the addition of a third agent, post-ASCT CR rates may reach 15% to 40%, whereas CR/VGPR rates are 50% to 75%. [77][78][79][80] However, it is clear that compared with VGPR, the CR level is associated with a better outcome. 25,81 Currently, CR defined by the absence of M-component on immunofixation and a normal bone marrow negative is the most widely accepted level.…”

Section: Which Level Of Response Is Necessary?mentioning

confidence: 99%

The role of complete response in multiple myeloma

Harousseau

Attal

Avet-Loiseau

2009

Blood

208

148

View full text Add to dashboard Cite

In multiple myeloma (MM), the impact of complete response (CR) could be shown only after introduction of high-dose therapy plus autologous stem cell transplantation (ASCT). In the context of ASCT, achieving CR (negative immunofixation and normal bone marrow) or at least very good partial response is associated with longer progression-free survival and in most studies longer survival. With novel agents, high CR rates are achieved and this prognostic impact of CR is being shown as well, both in relapsed and in newly diagnosed MM. However the benefit of CR achievement depends on the type of treatment and is not identical for all patients. In elderly patients, treatments inducing more CR may be more toxic. Although CR achievement is necessary in patients with poor-risk disease, it might not be as critical for long survival in more indolent MM. CR achievement is not the only objective of treatment because it is possible to further improve the depth of response and the outcome by continuing treatment after CR achievement. Finally, there are several levels of CR and in the future it will be necessary to confirm the prognostic impact of immunophenotypic or molecular CR or of CR defined by imaging procedures. (Blood. 2009;114: 3139-3146)

show abstract

Section: Which Level Of Response Is Necessary?mentioning

confidence: 99%

The role of complete response in multiple myeloma

Harousseau

Attal

Avet-Loiseau

2009

Blood

208

148

View full text Add to dashboard Cite

show abstract

“…Thalidomide is active in MM [3][4][5][6][7] and produces little hematologic toxicity, indicating that it may be preferred for use as induction therapy. 8 Previous studies evaluating thalidomide, as a component of induction therapy, have shown that it improves response rates 3,4,6,[9][10][11][12] and progression-free survival (PFS), 4,6,10,12,13 and provides similar 10,12,13 or improved 6 overall survival (OS) rates versus non-thalidomidecontaining regimens. Thalidomide also appears to be well tolerated in this setting and is associated with an acceptable rate of adverse events.…”

Section: Introductionmentioning

confidence: 99%

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

Morgan¹,

Davies²,

Gregory³

et al. 2011

Haematologica

149

111

View full text Add to dashboard Cite

The online version of this article has a Supplementary Appendix. BackgroundThalidomide 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 MethodsOral cyclophosphamide, thalidomide, and dexamethasone was compared with infusional cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. ResultsThe post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with cyclophosphamide-thalidomide-dexamethasone (n=555) versus cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44-2.55; P<0.0001. The complete response rates were 13.0% with cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophosphamide-vincristine-doxorubicin-dexamethasone (P=0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P=0.00052). Cyclophosphamidethalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine-doxorubicindexamethasone 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-thalidomidedexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. ConclusionsThe 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-dexamethasone may be considered an effective induction therapy option for patients with newly diagnosed multiple myeloma. ( ISRCTN: 68454111) Key words: multiple myeloma, thalidomide, induction therapy, CTD, CVAD.Citation: Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Johnson PRE, Rudin C, Drayson MT, Owen RG, Ross FM, Russell NH, Jackson GH, and

show abstract

“…22 Because of the limitations of our data set, it was not possible to discern an effect of differing induction regimens in this analysis, although published data in fact suggest that improved CR rates are more evident with the introduction of novel agents throughout the 2000s. [23][24][25][26] Alternatively, it is possible that this represents a technical issue of data collection and verification, as defining relapse as time points can be less definitive than defining death, features that underpin the calculation of PFS and OS, respectively. However, the reduced TTNT in 2005 compared with 1999 suggests that, in fact, the reduced time to relapse is clinically evident.…”

Section: Discussionmentioning

confidence: 99%