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 Szubert, Nuria Navarro Coy, Gordon Cook, Sylvia Feyler, Peter R E Johnson, Claudius Rudin, Mark T Drayson, Roger G Owen, Fiona M Ross, Nigel H Russell, Graham H Jackson, J Anthony Child, National Cancer Research Institute Haematological Oncology Clinical Studies Group, J Tighe, N Parry-Jones, I Singer, R Aitchison, J Seale, D Chan-Lam, C Rudin, P Cervi, C Singer, M Cook, Y Hasan, D W Milligan, M P Macheta, C Hoyle, M Grey, V Tringham, R Hall, L J Newton, R Evely, M Karanth, J Craig, A Whiteway, C Pocock, H Jackson, J Behrens, S Chown, E Lee, R Collin, P Bevan, M Hamblin, B Harrison, H Lumley, M Mahmoud, A Kamat, A McKernan, B Paul, A Moosa, J Neilson, K Gelly, J Beard, H Roddie, L Jones, C Rudin, R Neilson, G Summerfield, M Aldouri, G McQuaker, A Morrison, R Soutar, P Tansey, S Chown, V Tringham, S Sadullah, K Speed, G Robbins, G Bynoe, N Panoskaltsis, L Robinson, R Aitchison, H Sayala, I Grant, J A Ademokun, P Coates, Z Abboudi, G Cook, K Saravanamuttu, P Chu, B Hammer, P Cumber, J D Cavenagh, N Panoskaltsis, D Alderson, J Cavet, J Houghton, J Yin, J Tucker, W Bashi, A Wood, D White, G Jackson, C Tiplady, M Auger, N H Russell, M Narayanan, A Lakhani, A Sefcick, S Rule, A Bell, J Nicholson, A Brownell, H F Barker, J Beard, J Cullis, A Zaheer, J Snowden, S Bowcock, A Smith, D O'Brien, M Galloway, P Revell, M Haj, Z Maung, G Morgan, R Faulkner, S Al-Ismail, N Blesing, S Bolam, D Turner, A Kruger, D Gillett, R Kaczmarski, D Wright, A Borg, Y Hasan, P Cervi, G Galvani, S Basu, S Shafeek, A O'Driscoll, Gareth J Morgan, Faith E Davies, Walter M Gregory, Sue E Bell, Alexander J Szubert, Nuria Navarro Coy, Gordon Cook, Sylvia Feyler, Peter R E Johnson, Claudius Rudin, Mark T Drayson, Roger G Owen, Fiona M Ross, Nigel H Russell, Graham H Jackson, J Anthony Child, National Cancer Research Institute Haematological Oncology Clinical Studies Group, J Tighe, N Parry-Jones, I Singer, R Aitchison, J Seale, D Chan-Lam, C Rudin, P Cervi, C Singer, M Cook, Y Hasan, D W Milligan, M P Macheta, C Hoyle, M Grey, V Tringham, R Hall, L J Newton, R Evely, M Karanth, J Craig, A Whiteway, C Pocock, H Jackson, J Behrens, S Chown, E Lee, R Collin, P Bevan, M Hamblin, B Harrison, H Lumley, M Mahmoud, A Kamat, A McKernan, B Paul, A Moosa, J Neilson, K Gelly, J Beard, H Roddie, L Jones, C Rudin, R Neilson, G Summerfield, M Aldouri, G McQuaker, A Morrison, R Soutar, P Tansey, S Chown, V Tringham, S Sadullah, K Speed, G Robbins, G Bynoe, N Panoskaltsis, L Robinson, R Aitchison, H Sayala, I Grant, J A Ademokun, P Coates, Z Abboudi, G Cook, K Saravanamuttu, P Chu, B Hammer, P Cumber, J D Cavenagh, N Panoskaltsis, D Alderson, J Cavet, J Houghton, J Yin, J Tucker, W Bashi, A Wood, D White, G Jackson, C Tiplady, M Auger, N H Russell, M Narayanan, A Lakhani, A Sefcick, S Rule, A Bell, J Nicholson, A Brownell, H F Barker, J Beard, J Cullis, A Zaheer, J Snowden, S Bowcock, A Smith, D O'Brien, M Galloway, P Revell, M Haj, Z Maung, G Morgan, R Faulkner, S Al-Ismail, N Blesing, S Bolam, D Turner, A Kruger, D Gillett, R Kaczmarski, D Wright, A Borg, Y Hasan, P Cervi, G Galvani, S Basu, S Shafeek, A O'Driscoll
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.
Results: The 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 cyclophos-phamide-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). 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. (ISRCTN: 68454111).
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Source: PubMed