Efficacy and Prognostic Indicators of Isatuximab, Pomalidomide, and Dexamethasone (IsaPd) in Daratumumab‐Refractory Multiple Myeloma Patients: A Multicenter Real‐World Study

This multicenter real-world analysis evaluated the efficacy of isatuximab, pomalidomide, and dexamethasone (IsaPd) in 51 patients with multiple myeloma (MM) who were refractory to daratumumab (Dara-R). The majority were under 70 years old (60.8%), predominantly female (56.9%), and heavily pretreated, with 74.5% being triple-class refractory (TCR); 32.1% of the 28 patients with cytogenetic data had high-risk abnormalities. The overall response rate (ORR) was 56.9%, including 3 patients with stringent complete response (sCR), 4 with CR, and 7 with very good partial response (VGPR). Neither age, number of prior therapies, TCR status, nor time from Dara refractoriness to IsaPd initiation significantly affected response rates. Median progression-free survival (PFS) was 5.8 months, with a 12-month PFS probability of 30.6%. Baseline hemoglobin (Hb) levels were a key predictor of PFS: patients with Hb < 11.8 g/L had a 3.5-fold increased risk of progression, with a median PFS of 4.6 months compared to 22 months in those with higher Hb. Median overall survival (OS) was 21.0 months, with a 12-month OS probability of 63.4%. Lower Hb levels (< 11 g/L) were associated with a tenfold increased risk of mortality. Among the 28 patients who underwent FISH analysis, while no significant difference in mortality risk was observed, those with high-risk cytogenetic abnormalities exhibited a nearly tenfold increased risk of disease progression. These results suggest that IsaPd offers a meaningful option for Dara-R patients, with Hb levels serving as a critical predictor of both PFS and OS. However, PFS remains modest, underscoring the need for novel combination therapies.

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Publication Details

Journal
Hematological Oncology
Published
2025-02-03
DOI
https://doi.org/10.1002/hon.70042
Citations
9
Primary Topic
Multiple Myeloma Research and Treatments
Type
article
Field-Weighted Citation Impact
15.93
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article

Efficacy and Prognostic Indicators of Isatuximab, Pomalidomide, and Dexamethasone (IsaPd) in Daratumumab‐Refractory Multiple Myeloma Patients: A Multicenter Real‐World Study

Concetta Conticello, Elena Rivolti, Enrica Antonia Martino, Emilia Cotzia et al.
9 citations
Hematological Oncology
Multiple Myeloma Research and Treatments
15.93
article

Efficacy and Prognostic Indicators of Isatuximab, Pomalidomide, and Dexamethasone (IsaPd) in Daratumumab‐Refractory Multiple Myeloma Patients: A Multicenter Real‐World Study

Concetta Conticello, Elena Rivolti, Enrica Antonia Martino, Emilia Cotzia, Emiliano Barbieri, Annalisa Citro, Massimo Gentile, Angela Maria Quinto, Ombretta Annibali, Cirino Botta, Claudio De Magistris, Fortunato Morabito, Velia Bongarzoni, Raffaele Fontana, Francesco Di Raimondo, Anna Maria Cafro, Antonella Bruzzese, Antonino Neri, Silvia Mangiacavalli, Pellegrino Musto, Angela Amendola, Giuseppe Mele, Giuseppe Bertuglia, Katia Mancuso, Niccolò Bolli, Loredana Pettine, Valerio De Stefano, Elena Zamagni, Roberta Della Pepa, Anna Mele, Angela Rago, Daniele Derudas, Nicola Sgherza, Anna Furlan, Mónica Galli, Massimo Offidani, Ernesto Vigna, Paola Stefanoni, Sonia Morè, Maria Teresa Petrucci, Elena Rossi, Alessandro Corso
article en
9 citations

Abstract

This multicenter real-world analysis evaluated the efficacy of isatuximab, pomalidomide, and dexamethasone (IsaPd) in 51 patients with multiple myeloma (MM) who were refractory to daratumumab (Dara-R). The majority were under 70 years old (60.8%), predominantly female (56.9%), and heavily pretreated, with 74.5% being triple-class refractory (TCR); 32.1% of the 28 patients with cytogenetic data had high-risk abnormalities. The overall response rate (ORR) was 56.9%, including 3 patients with stringent complete response (sCR), 4 with CR, and 7 with very good partial response (VGPR). Neither age, number of prior therapies, TCR status, nor time from Dara refractoriness to IsaPd initiation significantly affected response rates. Median progression-free survival (PFS) was 5.8 months, with a 12-month PFS probability of 30.6%. Baseline hemoglobin (Hb) levels were a key predictor of PFS: patients with Hb < 11.8 g/L had a 3.5-fold increased risk of progression, with a median PFS of 4.6 months compared to 22 months in those with higher Hb. Median overall survival (OS) was 21.0 months, with a 12-month OS probability of 63.4%. Lower Hb levels (< 11 g/L) were associated with a tenfold increased risk of mortality. Among the 28 patients who underwent FISH analysis, while no significant difference in mortality risk was observed, those with high-risk cytogenetic abnormalities exhibited a nearly tenfold increased risk of disease progression. These results suggest that IsaPd offers a meaningful option for Dara-R patients, with Hb levels serving as a critical predictor of both PFS and OS. However, PFS remains modest, underscoring the need for novel combination therapies.

Hematological OncologyVol. 43(2)
University of Bergamo (IT), Marche Polytechnic University (IT), Azienda Ospedaliera San Giovanni Addolorata (IT), Agostino Gemelli University Polyclinic (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), University of Catania (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), ASL Roma (IT), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), Ospedale A. Perrino (IT), Federico II University Hospital (IT), Istituto di Ematologia di Bologna (IT), Istituto Tumori Bari (IT), Ospedale Annunziata di Cosenza (IT), Ospedali Riuniti San Giovanni di Dio e Ruggi d'Aragona (IT), Campus Bio Medico University Hospital (IT), Ca' Foncello Hospital (IT), Policlinico San Matteo Fondazione (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Azienda Sanitaria Locale Roma 3 (IT), Azienda Ospedaliera Ospedale Civile di Legnano (IT), University of Calabria (IT), University of Bari Aldo Moro (IT), University of Palermo (IT), University of Bologna (IT)
Good health and well-being
Openalex Percentile: Top 1%
Multiple Myeloma Research and Treatments
15.93
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