Efficacy and Safety of Isatuximab, Carfilzomib, and Dexamethasone (IsaKd) in Multiple Myeloma Patients at the First Relapse After Autologous Stem Cell Transplantation and Lenalidomide Maintenance: Results from the Multicenter, Real-Life AENEID Study

被引：1

作者：

Sgherza, Nicola ^{[1
]}

Battisti, Olga ^{[1
]}

Curci, Paola ^{[1
]}

Conticello, Concetta ^{[2
]}

Palmieri, Salvatore ^{[3
]}

Derudas, Daniele ^{[4
]}

Germano, Candida ^{[5
]}

Martino, Enrica Antonia ^{[6
]}

Mele, Giuseppe ^{[7
]}

Pepa, Roberta Della

Fazio, Francesca ^{[9
]}

Mele, Anna ^{[10
]}

Rossini, Bernardo ^{[11
]}

Palazzo, Giulia ^{[12
]}

Roccotelli, Daniela ^{[13
]}

Rasola, Simona ^{[14
]}

Petrucci, Maria Teresa ^{[9
]}

Pastore, Domenico ^{[7
]}

Tarantini, Giuseppe ^{[5
]}

Pane, Fabrizio ^{[8
]}

Gentile, Massimo ^{[6
,15
]}

Di Raimondo, Francesco ^{[2
,16
]}

Resta, Emanuela ^{[17
]}

Musto, Pellegrino ^{[1
,14
]}

机构：

[1] AOUC Policlin, Hematol & Stem Cell Transplantat Unit, I-70124 Bari, Italy

[2] Policlin G Rodolico San Marco, Div Hematol & Stem Cell Transplantat, I-95123 Catania, Italy

[3] Osped Cardarelli, Hematol Unit, I-80131 Naples, Italy

[4] Businco Hosp, Dept Hematol, I-09121 Cagliari, Italy

[5] Dimiccoli Hosp, Hematol Unit, I-70051 Barletta, Italy

[6] Azienda Osped Annunziata, Dept Oncohematol, Hematol Unit, I-87100 Cosenza, Italy

[7] Perrino Hosp, Hematol Unit, I-72100 Brindisi, Italy

[8] Univ Hosp Federico II, Dept Clin Med & Surg, Hematol, I-80131 Naples, Italy

[9] Sapienza Univ, Dept Translat & Precis Med Hematol, I-00185 Rome, Italy

[10] Cardinale Panico Hosp, Hematol Unit, I-70039 Tricase, Italy

[11] IRCCS Ist Tumori Giovanni Paolo II Bari, Hematol & Cell Therapy Unit, I-70124 Bari, Italy

[12] Osped G Moscati, Haematol Unit, I-74010 Taranto, Italy

[13] IRCSS Casa Sollievo Sofferenza, Dept Hematol & Bone Marrow Transplant, I-71013 Foggia, Italy

[14] Aldo Moro Univ, Sch Med, Dept Precis & Regenerat Med & Ionian Area, I-70121 Bari, Italy

[15] Univ Calabria, Dept Pharm Hlth & Nutr Sci, I-87036 Arcavacata Di Rende, Italy

[16] Univ Catania, Dept Gen Surg & Med Surg Specialties, Hematol Sect, I-95124 Catania, Italy

[17] Sapienza Univ, Dept Clin & Mol Med, I-00185 Rome, Italy

来源：

PHARMACEUTICALS | 2025年 / 18卷 / 04期

关键词：

first-relapsed multiple myeloma; second-line therapy; isatuximab-carfilzomib-dexamethasone; autologous stem cell transplantation; lenalidomide resistance; OPEN-LABEL; AUTO-SCT; DARATUMUMAB; BORTEZOMIB; OUTCOMES; THERAPY; ANTIBODY; ERA;

D O I：

10.3390/ph18040595

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Background: In the randomized, phase-3 IKEMA trial, the triplet isatuximab, carfilzomib, and dexamethasone (IsaKd) demonstrated superior clinical benefit compared to those of carfilzomib and dexamethasone alone in patients with relapsed/refractory multiple myeloma after 1-3 prior treatments. Methods: Our real-world, AENEID study aimed to evaluate the efficacy and safety of IsaKd in patients who relapsed after frontline lenalidomide treatment, poorly represented in the IKEMA trial. Specifically, in the present multicenter analysis, we enrolled eighty-two patients who received, between April 2022 and September 2024 and outside of clinical trials, at least one cycle of IsaKd as a second-line treatment at the first relapse after induction therapy, autologous stem cell transplantation (ASCT), and lenalidomide maintenance. Results: After a median follow-up time of 12.9 months (range, 1-77), the overall response rate, at least a very good partial response rate, and median progression-free survival time were 79.3%, 56.1%, and 24.4 months, respectively. This slightly lower performance compared to that in the IKEMA study may be attributed to the well-known poor prognostic impact of lenalidomide refractoriness (len-R), developed by all our patients during maintenance therapy, and to a higher proportion of patients with extramedullary disease present in our series, which was identified as the only factor significantly affecting the PFS in multivariable analysis. The median overall survival was not reached, as in the pivotal trial, while the 1-year survival probability was 85.1%. Regarding the safety profile, our findings were consistent with those of the IKEMA trial, with no new safety signals reported. Conclusions: These real-world data support the use of IsaKd as a valuable option for len-R MM patients relapsing after the first-line therapy, including ASCT and lenalidomide maintenance.

引用

页数：12

共 38 条

[1] Evaluation of isatuximab in patients with soft-tissue plasmacytomas: An analysis from ICARIA-MM and IKEMA [J].

Beksac, Meral ;

Spicka, Ivan ;

Hajek, Roman ;

Bringhen, Sara ;

Jelinek, Tomas ;

Martin, Thomas ;

Mikala, Gabor ;

Moreau, Philippe ;

Symeonidis, Argiris ;

Rawlings, Andreea M. ;

van de Velde, Helgi ;

Richardson, Paul G. .

LEUKEMIA RESEARCH, 2022, 122

[2] A Clinical and Correlative Study of Elotuzumab, Carfilzomib, Lenalidomide, and Dexamethasone (Elo-KRd) for Lenalidomide Refractory Multiple Myeloma in First Relapse [J].

Bhutani, Manisha ;

Foureau, David M. ;

Robinson, Myra ;

Guo, Fei ;

Fesenkova, Kateryna ;

Atrash, Shebli ;

Paul, Barry ;

Varga, Cindy ;

Friend, Reed ;

Pineda-Roman, Mauricio ;

Rigby, Katherine ;

Symanowski, James T. ;

Norek, Sarah ;

Tucker, Mallory R. ;

Druhan, Lawrence J. ;

Voorhees, Peter M. ;

Usmani, Saad Z. .

CLINICAL LYMPHOMA MYELOMA & LEUKEMIA, 2023, 23 (07) :535-+

[3] Treatment of Lenalidomide Exposed or Refractory Multiple Myeloma: Network Meta-Analysis of Lenalidomide-Sparing Regimens [J].

Botta, Cirino ;

Martino, Enrica Antonia ;

Conticello, Concetta ;

Mendicino, Francesco ;

Vigna, Ernesto ;

Romano, Alessandra ;

Palumbo, Giuseppe Antonio ;

Cerchione, Claudio ;

Martinelli, Giovanni ;

Morabito, Fortunato ;

Di Raimondo, Francesco ;

Gentile, Massimo .

FRONTIERS IN ONCOLOGY, 2021, 11

[4] Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study [J].

Cavo, Michele ;

Gay, Francesca ;

Beksac, Meral ;

Pantani, Lucia ;

Petrucci, Maria Teresa ;

Dimopoulos, Meletios A. ;

Dozza, Luca ;

van der Holt, Bronno ;

Zweegman, Sonja ;

Oliva, Stefania ;

van der Velden, Vincent H. J. ;

Zamagni, Elena ;

Palumbo, Giuseppe A. ;

Patriarca, Francesca ;

Montefusco, Vittorio ;

Galli, Monica ;

Maisnar, Vladimir ;

Gamberi, Barbara ;

Hansson, Markus ;

Belotti, Angelo ;

Pour, Ludek ;

Ypma, Paula ;

Grasso, Mariella ;

Croockewit, Alexsandra ;

Ballanti, Stelvio ;

Offidani, Massimo ;

Vincelli, Iolanda D. ;

Zambello, Renato ;

Liberati, Anna Marina ;

Andersen, Niels Frost ;

Broijl, Annemiek ;

Troia, Rossella ;

Pascarella, Anna ;

Benevolo, Giulia ;

Levin, Mark-David ;

Bos, Gerard ;

Ludwig, Heinz ;

Aquino, Sara ;

Morelli, Anna Maria ;

Wu, Ka Lung ;

Boersma, Rinske ;

Hajek, Roman ;

Durian, Marc ;

Borne, Peter A. von dem ;

di Toritto, Tommaso Caravita ;

Zander, Thilo ;

Specchia, Giorgina ;

Waage, Anders ;

Gimsing, Peter ;

Mellqvist, Ulf-Henrik .

LANCET HAEMATOLOGY, 2020, 7 (06) :E456-E468

[5] Additional copies of 1q negatively impact the outcome of multiple myeloma patients and induce transcriptomic deregulation in malignant plasma cells [J].

D'Agostino, Mattia ;

Rota-Scalabrini, Delia ;

Belotti, Angelo ;

Bertamini, Luca ;

Arigoni, Maddalena ;

De Sabbata, Giovanni ;

Pietrantuono, Giuseppe ;

Pascarella, Anna ;

Tosi, Patrizia ;

Pisani, Francesco ;

Pescosta, Norbert ;

Ruggeri, Marina ;

Rogers, Jennifer ;

Olivero, Martina ;

Garzia, Mariagrazia ;

Galieni, Piero ;

Annibali, Ombretta ;

Monaco, Federico ;

Liberati, Anna Marina ;

Palmieri, Salvatore ;

Stefanoni, Paola ;

Zamagni, Elena ;

Bruno, Benedetto ;

Calogero, Raffaele Adolfo ;

Boccadoro, Mario ;

Musto, Pellegrino ;

Gay, Francesca .

BLOOD CANCER JOURNAL, 2024, 14 (01)

[6] Clinical Efficacy of Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients [J].

De Novellis, Danilo ;

Derudas, Daniele ;

Vincelli, Donatella ;

Fontana, Raffaele ;

Della Pepa, Roberta ;

Palmieri, Salvatore ;

Accardi, Fabrizio ;

Rotondo, Francesco ;

Morelli, Emanuela ;

Gigliotta, Emilia ;

Roccotelli, Daniela ;

Marano, Luana ;

Barone, Maria Lucia ;

Cetani, Giusy ;

Esposito, Daniela ;

Lazzaro, Antonio ;

Delle Cave, Giuseppe ;

Serio, Bianca ;

Morini, Denise ;

Porrazzo, Marika ;

Urciuoli, Eleonora ;

Masucci, Chiara ;

Fanelli, Fulvia ;

Rizzo, Michela ;

Arcamone, Manuela ;

Trastulli, Fabio ;

Rocco, Stefano ;

Leone, Aldo ;

Bianco, Rosario ;

Salvatore, Flavia ;

Idato, Aurora ;

Sicari, Maria ;

Tosi, Patrizia ;

Rascato, Maria Gabriella ;

Di Perna, Maria ;

Falcone, Antonietta Pia ;

Morello, Lucia ;

Carlisi, Melania ;

Svanera, Gino ;

Annunziata, Mario ;

Frigeri, Ferdinando ;

Califano, Catello ;

Carella, Angelo Michele ;

Marcacci, Gianpaolo ;

Pane, Fabrizio ;

Risitano, Antonio Maria ;

Giudice, Valentina ;

Botta, Ciro ;

Selleri, Carmine .

EUROPEAN JOURNAL OF HAEMATOLOGY, 2025, 114 (01) :105-114

[7] SAR650984, A Novel Humanized CD38-Targeting Antibody, Demonstrates Potent Antitumor Activity in Models of Multiple Myeloma and Other CD38+ Hematologic Malignancies [J].

Deckert, Jutta ;

Wetzel, Marie-Cecile ;

Bartle, Laura M. ;

Skaletskaya, Anna ;

Goldmacher, Victor S. ;

Vallee, Francois ;

Zhou-Liu, Qing ;

Ferrari, Paul ;

Pouzieux, Stephanie ;

Lahoute, Charlotte ;

Dumontet, Charles ;

Plesa, Adriana ;

Chiron, Marielle ;

Lejeune, Pascale ;

Chittenden, Thomas ;

Park, Peter U. ;

Blanc, Veronique .

CLINICAL CANCER RESEARCH, 2014, 20 (17) :4574-4583

[8] Pomalidomide, bortezomib, and dexamethasone for multiple myeloma previously treated with lenalidomide (OPTIMISMM): outcomes by prior treatment at first relapse [J].

Dimopoulos, Meletios ;

Weisel, Katja ;

Moreau, Philippe ;

Anderson, Larry D., Jr. ;

White, Darrell ;

San-Miguel, Jesus ;

Sonneveld, Pieter ;

Engelhardt, Monika ;

Jenner, Matthew ;

Corso, Alessandro ;

Duerig, Jan ;

Pavic, Michel ;

Salomo, Morten ;

Casal, Eva ;

Srinivasan, Shankar ;

Yu, Xin ;

Nguyen, Tuong Vi ;

Biyukov, Tsvetan ;

Peluso, Teresa ;

Richardson, Paul .

LEUKEMIA, 2021, 35 (06) :1722-1731

[9]

Dimopoulos MA, 2021, LANCET ONCOL, V22, P801, DOI 10.1016/S1470-2045(21)00128-5

[10] Multiple Myeloma: EHA-ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up [J].

Dimopoulos, Meletios A. ;

Moreau, Philippe ;

Terpos, Evangelos ;

Mateos, Maria-Victoria ;

Zweegman, Sonja ;

Cooks, Gordon ;

Delforge, Michel ;

Hajek, Roman ;

Schjesvold, Fredrik ;

Cavo, Michele ;

Goldschmidt, Hartmut ;

Facon, Thierry ;

Einsele, Hermann ;

Boccadoro, Mario ;

San-Miguel, Jesus ;

Sonneveld, Pieter ;

Mey, Ulrich .

HEMASPHERE, 2021, 5 (02)

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