Continuous therapy in standard- and high-risk newly-diagnosed multiple myeloma: A pooled analysis of 2 phase III trials

M D'Agostino, L De Paoli, C Conticello, M Offidani, R Ria, MT Petrucci, S Spada, M Marcatti, L Catalano, M Gilestro, T Guglielmelli, L Baldini, B Gamberi, R Rizzi, G De Sabbata, N Di Renzo, F Patriarca, S Pezzatti, A Siniscalchi, R Ribolla & 5 others A Palumbo, V Montefusco, A Nagler, M Boccadoro, F Gay

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Abstract

Background: Risk-adapted therapy is a common strategy in curable hematologic malignancies: standard-risk patients receive less intensive treatment, whereas high-risk patients require a more intensive approach. This model cannot be applied in multiple myeloma (MM), which is still incurable. Continuous treatment (CT) is a key strategy for MM treatment, since it improves duration of remission. However, the role of CT according to standard- or high-risk baseline prognosis remains an open question. Patients and methods: We performed a pooled analysis of 2 phase III trials (GIMEMA-MM-03-05 and RV-MM-PI-209) that randomized patients to CT vs fixed-duration therapy (FDT). Results: In the overall patient population (n = 550), CT improved progression-free survival1 (PFS1) (HR 0.54), PFS2 (HR 0.61) and overall survival (OS) (HR 0.71) vs FDT. CT improved PFS1 both in R-ISS I (HR 0.49) and R-ISS II/III patients (HR 0.55). Four-year PFS1 was 38% in R-ISS II/III patients receiving CT and 25% in R-ISS I patients receiving FDT, with similar trends for PFS2 and OS. High-risk patients benefited more from proteasome-inhibitor plus immunomodulatory-based CT than immunomodulatory alone. Conclusion: Good prognosis patients receiving FDT lose their prognostic advantage over high-risk patients receiving CT and high-risk patients may benefit from more intensive maintenance including proteasome inhibitors and immunomodulators. © 2018 Elsevier B.V.
Original languageEnglish
Pages (from-to)9-16
Number of pages8
JournalCritical Reviews in Oncology/Hematology
Volume132
DOIs
Publication statusPublished - 2018

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Multiple Myeloma
Therapeutics
Proteasome Inhibitors
Survival
Immunologic Factors
Hematologic Neoplasms

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Continuous therapy in standard- and high-risk newly-diagnosed multiple myeloma: A pooled analysis of 2 phase III trials. / D'Agostino, M; De Paoli, L; Conticello, C; Offidani, M; Ria, R; Petrucci, MT; Spada, S; Marcatti, M; Catalano, L; Gilestro, M; Guglielmelli, T; Baldini, L; Gamberi, B; Rizzi, R; De Sabbata, G; Di Renzo, N; Patriarca, F; Pezzatti, S; Siniscalchi, A; Ribolla, R; Palumbo, A; Montefusco, V; Nagler, A; Boccadoro, M; Gay, F.

In: Critical Reviews in Oncology/Hematology, Vol. 132, 2018, p. 9-16.

Research output: Contribution to journalArticle

D'Agostino, M, De Paoli, L, Conticello, C, Offidani, M, Ria, R, Petrucci, MT, Spada, S, Marcatti, M, Catalano, L, Gilestro, M, Guglielmelli, T, Baldini, L, Gamberi, B, Rizzi, R, De Sabbata, G, Di Renzo, N, Patriarca, F, Pezzatti, S, Siniscalchi, A, Ribolla, R, Palumbo, A, Montefusco, V, Nagler, A, Boccadoro, M & Gay, F 2018, 'Continuous therapy in standard- and high-risk newly-diagnosed multiple myeloma: A pooled analysis of 2 phase III trials', Critical Reviews in Oncology/Hematology, vol. 132, pp. 9-16. https://doi.org/10.1016/j.critrevonc.2018.09.008
D'Agostino, M ; De Paoli, L ; Conticello, C ; Offidani, M ; Ria, R ; Petrucci, MT ; Spada, S ; Marcatti, M ; Catalano, L ; Gilestro, M ; Guglielmelli, T ; Baldini, L ; Gamberi, B ; Rizzi, R ; De Sabbata, G ; Di Renzo, N ; Patriarca, F ; Pezzatti, S ; Siniscalchi, A ; Ribolla, R ; Palumbo, A ; Montefusco, V ; Nagler, A ; Boccadoro, M ; Gay, F. / Continuous therapy in standard- and high-risk newly-diagnosed multiple myeloma: A pooled analysis of 2 phase III trials. In: Critical Reviews in Oncology/Hematology. 2018 ; Vol. 132. pp. 9-16.
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abstract = "Background: Risk-adapted therapy is a common strategy in curable hematologic malignancies: standard-risk patients receive less intensive treatment, whereas high-risk patients require a more intensive approach. This model cannot be applied in multiple myeloma (MM), which is still incurable. Continuous treatment (CT) is a key strategy for MM treatment, since it improves duration of remission. However, the role of CT according to standard- or high-risk baseline prognosis remains an open question. Patients and methods: We performed a pooled analysis of 2 phase III trials (GIMEMA-MM-03-05 and RV-MM-PI-209) that randomized patients to CT vs fixed-duration therapy (FDT). Results: In the overall patient population (n = 550), CT improved progression-free survival1 (PFS1) (HR 0.54), PFS2 (HR 0.61) and overall survival (OS) (HR 0.71) vs FDT. CT improved PFS1 both in R-ISS I (HR 0.49) and R-ISS II/III patients (HR 0.55). Four-year PFS1 was 38{\%} in R-ISS II/III patients receiving CT and 25{\%} in R-ISS I patients receiving FDT, with similar trends for PFS2 and OS. High-risk patients benefited more from proteasome-inhibitor plus immunomodulatory-based CT than immunomodulatory alone. Conclusion: Good prognosis patients receiving FDT lose their prognostic advantage over high-risk patients receiving CT and high-risk patients may benefit from more intensive maintenance including proteasome inhibitors and immunomodulators. {\circledC} 2018 Elsevier B.V.",
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TY - JOUR

T1 - Continuous therapy in standard- and high-risk newly-diagnosed multiple myeloma: A pooled analysis of 2 phase III trials

AU - D'Agostino, M

AU - De Paoli, L

AU - Conticello, C

AU - Offidani, M

AU - Ria, R

AU - Petrucci, MT

AU - Spada, S

AU - Marcatti, M

AU - Catalano, L

AU - Gilestro, M

AU - Guglielmelli, T

AU - Baldini, L

AU - Gamberi, B

AU - Rizzi, R

AU - De Sabbata, G

AU - Di Renzo, N

AU - Patriarca, F

AU - Pezzatti, S

AU - Siniscalchi, A

AU - Ribolla, R

AU - Palumbo, A

AU - Montefusco, V

AU - Nagler, A

AU - Boccadoro, M

AU - Gay, F

PY - 2018

Y1 - 2018

N2 - Background: Risk-adapted therapy is a common strategy in curable hematologic malignancies: standard-risk patients receive less intensive treatment, whereas high-risk patients require a more intensive approach. This model cannot be applied in multiple myeloma (MM), which is still incurable. Continuous treatment (CT) is a key strategy for MM treatment, since it improves duration of remission. However, the role of CT according to standard- or high-risk baseline prognosis remains an open question. Patients and methods: We performed a pooled analysis of 2 phase III trials (GIMEMA-MM-03-05 and RV-MM-PI-209) that randomized patients to CT vs fixed-duration therapy (FDT). Results: In the overall patient population (n = 550), CT improved progression-free survival1 (PFS1) (HR 0.54), PFS2 (HR 0.61) and overall survival (OS) (HR 0.71) vs FDT. CT improved PFS1 both in R-ISS I (HR 0.49) and R-ISS II/III patients (HR 0.55). Four-year PFS1 was 38% in R-ISS II/III patients receiving CT and 25% in R-ISS I patients receiving FDT, with similar trends for PFS2 and OS. High-risk patients benefited more from proteasome-inhibitor plus immunomodulatory-based CT than immunomodulatory alone. Conclusion: Good prognosis patients receiving FDT lose their prognostic advantage over high-risk patients receiving CT and high-risk patients may benefit from more intensive maintenance including proteasome inhibitors and immunomodulators. © 2018 Elsevier B.V.

AB - Background: Risk-adapted therapy is a common strategy in curable hematologic malignancies: standard-risk patients receive less intensive treatment, whereas high-risk patients require a more intensive approach. This model cannot be applied in multiple myeloma (MM), which is still incurable. Continuous treatment (CT) is a key strategy for MM treatment, since it improves duration of remission. However, the role of CT according to standard- or high-risk baseline prognosis remains an open question. Patients and methods: We performed a pooled analysis of 2 phase III trials (GIMEMA-MM-03-05 and RV-MM-PI-209) that randomized patients to CT vs fixed-duration therapy (FDT). Results: In the overall patient population (n = 550), CT improved progression-free survival1 (PFS1) (HR 0.54), PFS2 (HR 0.61) and overall survival (OS) (HR 0.71) vs FDT. CT improved PFS1 both in R-ISS I (HR 0.49) and R-ISS II/III patients (HR 0.55). Four-year PFS1 was 38% in R-ISS II/III patients receiving CT and 25% in R-ISS I patients receiving FDT, with similar trends for PFS2 and OS. High-risk patients benefited more from proteasome-inhibitor plus immunomodulatory-based CT than immunomodulatory alone. Conclusion: Good prognosis patients receiving FDT lose their prognostic advantage over high-risk patients receiving CT and high-risk patients may benefit from more intensive maintenance including proteasome inhibitors and immunomodulators. © 2018 Elsevier B.V.

U2 - 10.1016/j.critrevonc.2018.09.008

DO - 10.1016/j.critrevonc.2018.09.008

M3 - Article

VL - 132

SP - 9

EP - 16

JO - Critical Reviews in Oncology/Hematology

JF - Critical Reviews in Oncology/Hematology

SN - 1040-8428

ER -