Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial
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Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. / Goldschmidt, H; Lokhorst, H M; Mai, E K; van der Holt, B; Blau, I W; Zweegman, S; Weisel, K C; Vellenga, E; Pfreundschuh, M; Kersten, M J; Scheid, C; Croockewit, S; Raymakers, R; Hose, D; Potamianou, A; Jauch, A; Hillengass, J; Stevens-Kroef, M; Raab, M S; Broijl, A; Lindemann, H W; Bos, G M J; Brossart, P; van Marwijk Kooy, M; Ypma, P; Duehrsen, U; Schaafsma, R M; Bertsch, U; Hielscher, T; Jarari, Le; Salwender, H J; Sonneveld, P.
in: LEUKEMIA, Jahrgang 32, Nr. 2, 02.2018, S. 383-390.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial
AU - Goldschmidt, H
AU - Lokhorst, H M
AU - Mai, E K
AU - van der Holt, B
AU - Blau, I W
AU - Zweegman, S
AU - Weisel, K C
AU - Vellenga, E
AU - Pfreundschuh, M
AU - Kersten, M J
AU - Scheid, C
AU - Croockewit, S
AU - Raymakers, R
AU - Hose, D
AU - Potamianou, A
AU - Jauch, A
AU - Hillengass, J
AU - Stevens-Kroef, M
AU - Raab, M S
AU - Broijl, A
AU - Lindemann, H W
AU - Bos, G M J
AU - Brossart, P
AU - van Marwijk Kooy, M
AU - Ypma, P
AU - Duehrsen, U
AU - Schaafsma, R M
AU - Bertsch, U
AU - Hielscher, T
AU - Jarari, Le
AU - Salwender, H J
AU - Sonneveld, P
PY - 2018/2
Y1 - 2018/2
N2 - The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.76, 95% confidence interval (95% CI) of 0.65-0.89, P=0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74-1.08, P=0.24). The incidence of SPM were similar between the two arms (7% each, P=0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size ⩾10%) and renal impairment at baseline (serum creatinine >2 mg dl-1) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR=1.02, P=0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.
AB - The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.76, 95% confidence interval (95% CI) of 0.65-0.89, P=0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74-1.08, P=0.24). The incidence of SPM were similar between the two arms (7% each, P=0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size ⩾10%) and renal impairment at baseline (serum creatinine >2 mg dl-1) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR=1.02, P=0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.
KW - Adolescent
KW - Adult
KW - Aged
KW - Bortezomib
KW - Chromosome Aberrations
KW - Female
KW - Follow-Up Studies
KW - Hematopoietic Stem Cell Transplantation
KW - Humans
KW - Male
KW - Melphalan
KW - Middle Aged
KW - Multiple Myeloma
KW - Prognosis
KW - Progression-Free Survival
KW - Thalidomide
KW - Transplantation, Autologous
KW - Young Adult
KW - Clinical Trial, Phase III
KW - Journal Article
KW - Multicenter Study
KW - Randomized Controlled Trial
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/leu.2017.211
DO - 10.1038/leu.2017.211
M3 - SCORING: Journal article
C2 - 28761118
VL - 32
SP - 383
EP - 390
JO - LEUKEMIA
JF - LEUKEMIA
SN - 0887-6924
IS - 2
ER -