دورية أكاديمية
Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended follow-up of a multicenter, retrospective real-world experience with 321 cases outside of controlled clinical trials.
| العنوان: | Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended follow-up of a multicenter, retrospective real-world experience with 321 cases outside of controlled clinical trials. |
|---|---|
| المؤلفون: | Martino EA; Department of Onco-hematology, Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy., Palmieri S; Hematology Unit, Ospedale Cardarelli, Napoli, Italy., Galli M; Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni, Bergamo, Italy., Derudas D; Department of Hematology, Businco Hospital, Cagliari, Italy., Mina R; Division of Hematology, AOU Città della Salute e della Scienza di Torino, University of Torino, Torino, Italy., Della Pepa R; Department of Clinical Medicine and Surgery, Hematology Unit, University of Naples 'Federico II', Naples, Italy., Zambello R; Department of Medicine, University of Padova, Hematology Unit, Padova, Italy.; Veneto Institute of Molecular Medicine, Padova, Italy., Vigna E; Department of Onco-hematology, Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy., Bruzzese A; Department of Onco-hematology, Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy., Mangiacavalli S; Division of Hematology, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy., Zamagni E; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', Bologna, Italy.; Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy., Califano C; Onco-Hematology Unit, 'A. Tortora' Hospital, Pagani, Italy., Musso M; Department of Oncology, Onco-Hematology Unit and TMO U.O.C., Palermo, Italy., Conticello C; Division of Hematology, Azienda Policlinico-S. Marco, University of Catania, Catania, Italy., Cerchione C; Hematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Mele G; Department of Hematology, Hospital Perrino, Brindisi, Italy., Di Renzo N; Department of Hematology, Hospital Vito Fazzi, Lecce, Italy., Offidani M; Hematology Unit, AOU delle Marche, Ancona, Italy., Tarantini G; Hematology Unit, 'Dimiccoli' Hospital, Barletta (BAT), Italy., Casaluci GM; Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy., Rago A; UOSD Ematologia, Rome, Italy., Ria R; Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro Medical School, Internal Medicine 'G. Baccelli'; CITEL, Bari, Italy.; Interdepartmental Centre for Research in Telemedicine, University of Bari Aldo Moro, Bari, Italy., Uccello G; Hematology Department, G. Garibaldi Hospital, Catania, Italy., Barilà G; Hematology Unit, Ospedale San Bortolo, Vicenza, Italy., Palumbo G; Department of Hematology, Hospital University Riuniti, Foggia, Italy., Pettine L; Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy., Vincelli ID; Department of Hemato-Oncology and Radiotherapy, Hematology Unit, Great Metropolitan Hospital 'Bianchi-Melacrino-Morelli', Reggio Calabria, Italy., Brunori M; Internal Medicine, Ospedale Santa Croce, Fano, Italy., Accardi F; Department of Hematology I, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy., Amico V; UOSD Ematologia, AORN San Pio, Benevento, Italy., Amendola A; Hematology Unit, Azienda Ospedaliera Regionale 'San Carlo', Potenza, Italy., Fontana R; Hematology and Transplant Center, University Hospital 'San Giovanni di Dio e Ruggi d'Aragona', Salerno, Italy., Bongarzoni V; Department of Hematology, San Giovanni-Addolorata Hospital, Rome, Italy., Rossini B; Hematology and Cell Therapy Unit, IRCCS Istituto Tumori 'Giovanni Paolo II' Bari, Bari, Italy., Cotzia E; Section of Hematology- Ospedale E. Muscatello-Augusta, Siracusa, Italy., Gozzetti A; Hematology, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy., Rizzi R; Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico Bari, Bari, Italy.; Department of Precision and Regenerative Medicine and Ionian Area, 'Aldo Moro' University School of Medicine, Bari, Italy., Sgherza N; Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico Bari, Bari, Italy., Reddiconto G; Department of Hematology, Hospital Vito Fazzi, Lecce, Italy., Maroccia A; Hematology Unit - Ospedale dell'Angelo Azienda ULSS n.3 Serenissima, Venezia Mestre, Italy., Franceschini L; Lymphoproliferative Diseases Unit, Tor Vergata University Hospital, Rome, Italy., Bertuglia G; Dipartimento di Oncologia ed Ematologia SC Ematologia 1 A.O. Citta' della Salute e della Scienza di Torino P.O. Molinette, Torino, Italy., Nappi D; Hematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Barbieri E; Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy., Gamberi B; Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy., Petrucci MT; Department of Translational and Precision Medicine, Hematology Azienda Policlinico Umberto I Sapienza University of Rome, Rome, Italy., Di Raimondo F; Division of Hematology, Azienda Policlinico-S. Marco, University of Catania, Catania, Italy., Neri A; Scientific Directorate, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy., Morabito F; Gruppo Amici Dell'Ematologia Foundation-GrADE, Reggio Emilia, Italy., Musto P; Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico Bari, Bari, Italy.; Department of Precision and Regenerative Medicine and Ionian Area, 'Aldo Moro' University School of Medicine, Bari, Italy., Gentile M; Department of Onco-hematology, Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.; Department of Pharmacy, Health and Nutritional Science, University of Calabria, Rende, Italy. |
| المصدر: | Hematological oncology [Hematol Oncol] 2024 Jul; Vol. 42 (4), pp. e3290. |
| نوع المنشور: | Journal Article; Multicenter Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 8307268 Publication Model: Print Cited Medium: Internet ISSN: 1099-1069 (Electronic) Linking ISSN: 02780232 NLM ISO Abbreviation: Hematol Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford, England : Wiley-Blackwell, c1983- |
| مواضيع طبية MeSH: | Multiple Myeloma*/drug therapy , Multiple Myeloma*/mortality , Multiple Myeloma*/pathology , Dexamethasone*/administration & dosage , Dexamethasone*/adverse effects , Dexamethasone*/therapeutic use , Antibodies, Monoclonal, Humanized*/administration & dosage , Antibodies, Monoclonal, Humanized*/therapeutic use , Antibodies, Monoclonal, Humanized*/adverse effects , Antineoplastic Combined Chemotherapy Protocols*/therapeutic use , Antineoplastic Combined Chemotherapy Protocols*/adverse effects , Thalidomide*/analogs & derivatives , Thalidomide*/administration & dosage , Thalidomide*/adverse effects , Thalidomide*/therapeutic use, Humans ; Male ; Female ; Aged ; Middle Aged ; Retrospective Studies ; Follow-Up Studies ; Aged, 80 and over ; Adult ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/pathology ; Drug Resistance, Neoplasm ; Survival Rate |
| مستخلص: | The ELOQUENT-3 trial demonstrated the superiority of the combination of elotuzumab, pomalidomide, and dexamethasone (EloPd) in terms of efficacy and safety, compared to Pd in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor. The present study is an 18-month follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloPd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 17.7 months, 213 patients (66.4%) experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 7.5 and 19.2 months, respectively. The updated multivariate analysis showed a significant reduction of PFS benefit magnitude both in advanced International Staging System (ISS) (II and III) stages and previous exposure to daratumumab cases. Instead, advanced ISS (II and III) stages and more than 2 previous lines of therapy maintained an independent prognostic impact on OS. Major adverse events included grade three-fourths neutropenia (24.9%), anemia (13.4%), lymphocytopenia (15.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 19.3% and 8.7%, respectively. A slight increase in the incidence of neutropenia and lymphocytopenia was registered with longer follow-up. In conclusion, our real-world study still confirms that EloPd is a safe and possible therapeutic choice for RRMM. Nevertheless, novel strategies are desirable for those patients exposed to daratumumab. (© 2024 John Wiley & Sons Ltd.) |
| References: | Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28(5):1122‐1128. https://doi.org/10.1038/leu.2013.313. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111(5):2516‐2520. https://doi.org/10.1182/blood‐2007‐10‐116129. Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA‐ESMO Clinical Practice Guidelines for diagnosis, treatment and follow‐up (dagger). Ann Oncol. 2021;32(3):309‐322. https://doi.org/10.1016/j.annonc.2020.11.014. Nooka AK, Kaufman JL, Hofmeister CC, et al. Daratumumab in multiple myeloma. Cancer. 2019;125(14):2364‐2382. https://doi.org/10.1002/cncr.32065. Bruzzese A, Martino EA, Vigna E, et al. Elotuzumab in multiple myeloma. Expert Opin Biol Ther. 2023;23(1):7‐10. https://doi.org/10.1080/14712598.2022.2145882. Durer C, Durer S, Lee S, et al. Treatment of relapsed multiple myeloma: evidence‐based recommendations. Blood Rev. 2019;31:100616. https://doi.org/10.1016/j.blre.2019.100616. Collins SM, Bakan CE, Swartzel GD, et al. Elotuzumab directly enhances NK cell cytotoxicity against myeloma via CS1 ligation: evidence for augmented NK cell function complementing ADCC. Cancer Immunol Immunother. 2013;62(12):1841‐1849. https://doi.org/10.1007/s00262‐013‐1493‐8. Hsi ED, Steinle R, Balasa B, et al. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res. 2008;14(9):2775‐2784. https://doi.org/10.1158/1078‐0432.ccr‐07‐4246. Balasa B, Yun R, Belmar NA, et al. Elotuzumab enhances natural killer cell activation and myeloma cell killing through interleukin‐2 and TNF‐α pathways. Cancer Immunol Immunother. 2015;64(1):61‐73. https://doi.org/10.1007/s00262‐014‐1610‐3. Dimopoulos MA, Lonial S, Betts KA, et al. Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended 4‐year follow‐up and analysis of relative progression‐free survival from the randomized ELOQUENT‐2 trial. Cancer. 2018;124(20):4032‐4043. https://doi.org/10.1002/cncr.31680. Gentile M, Specchia G, Derudas D, et al. Elotuzumab, lenalidomide, and dexamethasone as salvage therapy for patients with multiple myeloma: Italian, multicenter, retrospective clinical experience with 300 cases outside of controlled clinical trials. Haematologica. 2021;106(1):291‐294. https://doi.org/10.3324/haematol.2019.241513. Bruzzese A, Derudas D, Galli M, et al. Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended 3‐year follow‐up of a multicenter, retrospective clinical experience with 319 cases outside of controlled clinical trials. Hematol Oncol. 2022;40(4):704‐715. https://doi.org/10.1002/hon.3031. Morabito F, Zamagni E, Conticello C, et al. Adjusted comparison between elotuzumab and carfilzomib in combination with lenalidomide and dexamethasone as salvage therapy for multiple myeloma patients. Eur J Haematol. 2022;108(3):178‐189. https://doi.org/10.1111/ejh.13723. Morabito F, Zamagni E, Conticello C, et al. Survival risk scores for real‐life relapsed/refractory multiple myeloma patients receiving elotuzumab or carfilzomib in combination with lenalidomide and dexamethasone as salvage therapy: analysis of 919 cases outside clinical trials. Front Oncol. 2022;12:890376. https://doi.org/10.3389/fonc.2022.890376. Lopez‐Girona A, Mendy D, Ito T, et al. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia. 2012;26(11):2326‐2335. https://doi.org/10.1038/leu.2012.119. Uccello G, Petrungaro A, Mazzone C, et al. Pomalidomide in multiple myeloma. Expert Opin Pharmacother. 2017;18(2):133‐137. https://doi.org/10.1080/14656566.2016.1274973. Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab plus pomalidomide and dexamethasone for relapsed/refractory multiple myeloma: final overall survival analysis from the randomized phase II ELOQUENT‐3 trial. J Clin Oncol. 2023;41(3):568‐578. https://doi.org/10.1200/jco.21.02815. Gentile M, Vigna E, Palmieri S, et al. Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: a multicenter, retrospective, real‐world experience with 200 cases outside of controlled clinical trials. Haematologica. 2024;109(1):245‐255. https://doi.org/10.3324/haematol.2023.283251. European Medicines. Agency Empliciti, INN‐Elotuzumab. Accessed on 20 January 2024. https://www.ema.europa.eu/en/documents/product‐information/emplicitiepar‐product‐information_it.pdf. Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20(9):1467‐1473. https://doi.org/10.1038/sj.leu.2404284. Rajkumar SV, Harousseau JL, Durie B, et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011;117(18):4691‐4695. https://doi.org/10.1182/blood‐2010‐10‐299487. Parikh RH, Lonial S. Chimeric antigen receptor T‐cell therapy in multiple myeloma: a comprehensive review of current data and implications for clinical practice. CA Cancer J Clin. 2023;73(3):275‐285. https://doi.org/10.3322/caac.21771. Martino EA, Bruzzese A, Labanca C, et al. Teclistamab‐cqyv in multiple myeloma. Eur J Haematol. 2023;112(3):320‐327. https://doi.org/10.1111/ejh.14121. Martino EA, Bruzzese A, Iaccino E, et al. Belantamab mafodotin in multiple myeloma. Expert Opin Biol Ther. 2023;23(11):1043‐1047. https://doi.org/10.1080/14712598.2023.2218543. Ziccheddu B, Giannotta C, D'Agostino M, et al. Genomic and immune determinants of resistance to anti‐CD38 monoclonal antibody‐based therapy in relapsed refractory multiple myeloma. medRxiv. 2023. 12.04.23299287. Chng WJ, Dispenzieri A, Chim CS, et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014;28(2):269‐277. https://doi.org/10.1038/leu.2013.247. A Study of Iberdomide (CC‐220) in Combination with Elotuzumab and Dexamethasone for Relapsed/Refractory Multiple Myeloma (CC‐220). ClinicalTrials.Gov Identifier: NCT 05560399. Isatuximab P. Elotuzumab and Dexamethasone in Relapsed And/or Refractory Multiple Myeloma (IMPEDE). ClinicalTrials.Gov Identifier: NCT 04835129. Novel Combination of Belantamab Mafodotin and Elotuzumab to Enhance Therapeutic Efficacy in Multiple Myeloma ClinicalTrials.Gov Identifier: NCT 05002816. |
| معلومات مُعتمدة: | Progetto Ricerca Finalizzata PNRR-MAD-2022-12375673, Italian Ministry of Health, Rome, Italy. |
| فهرسة مساهمة: | Keywords: dexamethasone; elotuzumab; multiple myeloma; pomalidomide; salvage therapy |
| المشرفين على المادة: | D2UX06XLB5 (pomalidomide) 7S5I7G3JQL (Dexamethasone) 0 (Antibodies, Monoclonal, Humanized) 1351PE5UGS (elotuzumab) 4Z8R6ORS6L (Thalidomide) |
| تواريخ الأحداث: | Date Created: 20240531 Date Completed: 20240531 Latest Revision: 20240531 |
| رمز التحديث: | 20240531 |
| DOI: | 10.1002/hon.3290 |
| PMID: | 38818978 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1099-1069 |
|---|---|
| DOI: | 10.1002/hon.3290 |