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

• Published in: Critical reviews in oncology/hematology 2018-12, Vol.132, p.9-16
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Clinical Trials, Phase III as Topic; Continuous therapy; Drug Administration Schedule; High risk; Humans; Multiple myeloma; Multiple Myeloma - diagnosis; Multiple Myeloma - drug therapy; Newly diagnosed; Novel agents; Prognosis; Randomized Controlled Trials as Topic
• ISSN: 1040-8428; 1879-0461
• DOI: 10.1016/j.critrevonc.2018.09.008

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. 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). 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. 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.