An Italian real-world multicenter study of patients with refractory/relapsed functional high-risk multiple myeloma patients treated with second-line therapies

Functional high risk multiple myeloma (FHRMM) remains a challenging entity with poor outcomes and limited survival, and there is no international consensus on optimal second-line therapeutic strategies in relapsed/refractory patients. In this multicenter real-world retrospective study, we investigated clinical characteristics and outcomes of a total of 62 FHRMM patients previously treated with a first-line daratumumab-based quadruplet regimen or who relapsed within 12 months after frontline autologous stem cell transplantation (ASCT). In our cohort, the overall response rate was 61%, with 42% of patients achieving a very good partial response (VGPR) or better. Similarly, median progression-free survival (PFS) was not reached with an estimated 12-month PFS rate of 54%, as well as median overall survival (OS) with a 12-month OS rate of 72%. Factors associated with worse PFS included extramedullary disease, prior lenalidomide maintenance, lack of ASCT consolidation, an ECOG score ≥ 2, advanced disease stage, and salvage therapy without carfilzomib-lenalidomide-dexamethasone. In conclusion, second-line management of FHRMM following daratumumab-bortezomib-thalidomide-dexamethasone induction is highly challenging and variable across centers, due to the lack of standardized international guidelines. Carfilzomib-based regimens demonstrated some clinical benefits, especially in lenalidomide-naïve patients; however, outcomes remained suboptimal in FHRMM population who may benefit from novel therapies administered as earlier treatment lines. Larger prospective trials are needed to optimize FHRMM clinical management and improve patient outcomes.

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Publication Details

Journal
Annals of Hematology
Published
2025-09-01
DOI
https://doi.org/10.1007/s00277-025-06572-y
Primary Topic
Multiple Myeloma Research and Treatments
Type
article
Field-Weighted Citation Impact
0.00

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article

An Italian real-world multicenter study of patients with refractory/relapsed functional high-risk multiple myeloma patients treated with second-line therapies

Emilia Gigliotta, Luana Marano, Angelo Michele Carella, Cirino Botta et al.
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Annals of Hematology
Multiple Myeloma Research and Treatments
article

An Italian real-world multicenter study of patients with refractory/relapsed functional high-risk multiple myeloma patients treated with second-line therapies

Emilia Gigliotta, Luana Marano, Angelo Michele Carella, Cirino Botta, Antonietta Falcone, Daniela Roccotelli, Manuela Arcamone, Rosario Bianco, Mario Annunziata, Michela Rizzo, Raffaele Fontana, Eleonora Urciuoli, Valentina Giudice, Fabrizio Accardi, Rossella Iula, Antonio M. Risitano, Aldo Leone, Roberta Della Pepa, Fabrizio Pane, Lucia Morello, Antonio Lazzaro, Daniela Espósito, Maria Gabriella Rascato, Maria Lucia Barone, Salvatore Palmieri, Emanuela Morelli, Anna Maria Della Corte, Carmine Selleri, Matteo Bonanni, Daniele Derudas, Ferdinando Frigeri, Chiara Masucci, Catello Califano, Maria Di Perna, Anna Dandolo, Bianca Serio, Danilo De Novellis, Gianpaolo Marcacci, Stefano Rocco, Nunziata Giuseppe Rodolfo
article en

Abstract

Functional high risk multiple myeloma (FHRMM) remains a challenging entity with poor outcomes and limited survival, and there is no international consensus on optimal second-line therapeutic strategies in relapsed/refractory patients. In this multicenter real-world retrospective study, we investigated clinical characteristics and outcomes of a total of 62 FHRMM patients previously treated with a first-line daratumumab-based quadruplet regimen or who relapsed within 12 months after frontline autologous stem cell transplantation (ASCT). In our cohort, the overall response rate was 61%, with 42% of patients achieving a very good partial response (VGPR) or better. Similarly, median progression-free survival (PFS) was not reached with an estimated 12-month PFS rate of 54%, as well as median overall survival (OS) with a 12-month OS rate of 72%. Factors associated with worse PFS included extramedullary disease, prior lenalidomide maintenance, lack of ASCT consolidation, an ECOG score ≥ 2, advanced disease stage, and salvage therapy without carfilzomib-lenalidomide-dexamethasone. In conclusion, second-line management of FHRMM following daratumumab-bortezomib-thalidomide-dexamethasone induction is highly challenging and variable across centers, due to the lack of standardized international guidelines. Carfilzomib-based regimens demonstrated some clinical benefits, especially in lenalidomide-naïve patients; however, outcomes remained suboptimal in FHRMM population who may benefit from novel therapies administered as earlier treatment lines. Larger prospective trials are needed to optimize FHRMM clinical management and improve patient outcomes.

Annals of HematologyVol. 104(9)
Ospedale Antonio Cardarelli (IT), Ospedale Vincenzo Cervello (IT), Azienda Ospedaliera S.Giuseppe Moscati (IT), CTO Andrea Alesini (IT), Guglielmo da Saliceto Hospital (IT), Ospedale Sant'Anna (IT), Gruppo Italiano per il Trapianto di Midollo Osseo (IT)
Università degli Studi di Salerno
Openalex Percentile: Top 69%
Multiple Myeloma Research and Treatments
DOIOpen Access PDFOpenAlex
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