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

Mattia D'Agostino, Lorenzo De Paoli, Concetta Conticello, Massimo Offidani, Roberto Ria, Maria Teresa Petrucci, Stefano Spada, Magda Marcatti, Lucio Catalano, Milena Gilestro, Tommasina Guglielmelli, Luca Baldini, Barbara Gamberi, Rita Rizzi, Giovanni De Sabbata, Nicola Di Renzo, Francesca Patriarca, Sara Pezzatti, Agostina Siniscalchi, Rossella RibollaAntonio Palumbo, Vittorio Montefusco, Arnon Nagler, Mario Boccadoro, Francesca Gay

Research output: Contribution to journalReview article

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)9-16
Number of pages8
JournalCritical Reviews in Oncology/Hematology
Volume132
DOIs
Publication statusPublished - Dec 1 2018

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Multiple Myeloma
Therapeutics
Proteasome Inhibitors
Survival
Immunologic Factors
Hematologic Neoplasms

Keywords

  • Continuous therapy
  • High risk
  • Multiple myeloma
  • Newly diagnosed
  • Novel agents

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Continuous therapy in standard- and high-risk newly-diagnosed multiple myeloma : A pooled analysis of 2 phase III trials. / D'Agostino, Mattia; De Paoli, Lorenzo; Conticello, Concetta; Offidani, Massimo; Ria, Roberto; Petrucci, Maria Teresa; Spada, Stefano; Marcatti, Magda; Catalano, Lucio; Gilestro, Milena; Guglielmelli, Tommasina; Baldini, Luca; Gamberi, Barbara; Rizzi, Rita; De Sabbata, Giovanni; Di Renzo, Nicola; Patriarca, Francesca; Pezzatti, Sara; Siniscalchi, Agostina; Ribolla, Rossella; Palumbo, Antonio; Montefusco, Vittorio; Nagler, Arnon; Boccadoro, Mario; Gay, Francesca.

In: Critical Reviews in Oncology/Hematology, Vol. 132, 01.12.2018, p. 9-16.

Research output: Contribution to journalReview article

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, Mattia ; De Paoli, Lorenzo ; Conticello, Concetta ; Offidani, Massimo ; Ria, Roberto ; Petrucci, Maria Teresa ; Spada, Stefano ; Marcatti, Magda ; Catalano, Lucio ; Gilestro, Milena ; Guglielmelli, Tommasina ; Baldini, Luca ; Gamberi, Barbara ; Rizzi, Rita ; De Sabbata, Giovanni ; Di Renzo, Nicola ; Patriarca, Francesca ; Pezzatti, Sara ; Siniscalchi, Agostina ; Ribolla, Rossella ; Palumbo, Antonio ; Montefusco, Vittorio ; Nagler, Arnon ; Boccadoro, Mario ; Gay, Francesca. / 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.",
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T1 - Continuous therapy in standard- and high-risk newly-diagnosed multiple myeloma

T2 - A pooled analysis of 2 phase III trials

AU - D'Agostino, Mattia

AU - De Paoli, Lorenzo

AU - Conticello, Concetta

AU - Offidani, Massimo

AU - Ria, Roberto

AU - Petrucci, Maria Teresa

AU - Spada, Stefano

AU - Marcatti, Magda

AU - Catalano, Lucio

AU - Gilestro, Milena

AU - Guglielmelli, Tommasina

AU - Baldini, Luca

AU - Gamberi, Barbara

AU - Rizzi, Rita

AU - De Sabbata, Giovanni

AU - Di Renzo, Nicola

AU - Patriarca, Francesca

AU - Pezzatti, Sara

AU - Siniscalchi, Agostina

AU - Ribolla, Rossella

AU - Palumbo, Antonio

AU - Montefusco, Vittorio

AU - Nagler, Arnon

AU - Boccadoro, Mario

AU - Gay, Francesca

PY - 2018/12/1

Y1 - 2018/12/1

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.

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.

KW - Continuous therapy

KW - High risk

KW - Multiple myeloma

KW - Newly diagnosed

KW - Novel agents

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