{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T07:28:46Z","timestamp":1774510126070,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100003887","name":"International Myeloma Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100003887","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Although triplet regimens have been shown to be effective and safe in pivotal studies involving frail patients with multiple myeloma (MM), their use in frail patients is often avoided in real-world settings. As MM treatment progresses and options increase, it is crucial to clarify the efficacy and safety of triplet regimens in clinical practice. Methods: Patients who received anti-CD38 antibody-containing triplet regimens at our hospital from 2017 to 2024 were divided into frail and non-frail groups based on the IMWG simplified frailty scale and retrospectively analyzed. Results: In the 150 patients included, the median age was 76 years for the frail group and 69 years for the non-frail group. Daratumumab-containing triplet regimens were given to 108 (82 frail) patients, and isatuximab-containing triplet regimens were given to 42 patients (18 frail). Progression-free survival and overall survival for the frail and non-frail groups were 15.4 vs. 11.4 months and 45.6 vs. 40.7 months, respectively; the overall response rate was 76% vs. 68%, with no significant differences. Prognoses by regimen were also not significantly different. There were no significant differences in any adverse events and grade 3\u20134 hematological and non-hematological adverse events between the two groups. This analysis showed that, in frail MM patients who were eligible to receive triplet regimens, anti-CD38 antibody-containing triplet regimens were as effective and safe as in non-frail patients. Conclusions: In conclusion, these regimens may be viable options for frail patients, provided that appropriate management, including withdrawal of therapeutic agents, dose reduction, and infection control, is rigorously performed, as for non-frail patients.<\/jats:p>","DOI":"10.3390\/cancers18071048","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T12:58:59Z","timestamp":1774357139000},"page":"1048","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Anti-CD38 Antibody-Containing Triplet Regimens in Frail Patients with Multiple Myeloma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6970-9881","authenticated-orcid":false,"given":"Hirono","family":"Iriuchishima","sequence":"first","affiliation":[{"name":"Department of Clinical Research, NHO Shibukawa Medical Center, Shibukawa 377-0280, Gunma, Japan"},{"name":"Department of Hematology, NHO Shibukawa Medical Center, Shibukawa 377-0280, Gunma, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0314-2892","authenticated-orcid":false,"given":"Akio","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Hematology, NHO Shibukawa Medical Center, Shibukawa 377-0280, Gunma, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Mihara","sequence":"additional","affiliation":[{"name":"Department of Hematology, NHO Shibukawa Medical Center, Shibukawa 377-0280, Gunma, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhei","family":"Kanaya","sequence":"additional","affiliation":[{"name":"Department of Hematology, NHO Shibukawa Medical Center, Shibukawa 377-0280, Gunma, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Yoshizawa","sequence":"additional","affiliation":[{"name":"Department of Hematology, NHO Shibukawa Medical Center, Shibukawa 377-0280, Gunma, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Isoda","sequence":"additional","affiliation":[{"name":"Department of Hematology, NHO Shibukawa Medical Center, Shibukawa 377-0280, Gunma, Japan"},{"name":"Department of Hematology, Hoshi Clinic, Maebashi 379-2131, Gunma, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9791-0139","authenticated-orcid":false,"given":"Morio","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Hematology, NHO Shibukawa Medical Center, Shibukawa 377-0280, Gunma, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Padala, S.A., Barsouk, A., Barsouk, A., Rawla, P., Vakiti, A., Kolhe, R., Kota, V., and Ajebo, G.H. (2021). Epidemiology, Staging, and Management of Multiple Myeloma. Med. Sci., 9.","DOI":"10.3390\/medsci9010003"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41408-022-00779-2","article-title":"The Prevalence and Outcomes of Frail Older Adults in Clinical Trials in Multiple Myeloma: A Systematic Review","volume":"13","author":"Mian","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1182\/blood-2014-12-615187","article-title":"Geriatric Assessment Predicts Survival and Toxicities in Elderly Myeloma Patients: An International Myeloma Working Group Report","volume":"125","author":"Palumbo","year":"2015","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"910","DOI":"10.3324\/haematol.2016.162693","article-title":"A Concise Revised Myeloma Comorbidity Index as a Valid Prognostic Instrument in a Large Cohort of 801 Multiple Myeloma Patients","volume":"102","author":"Engelhardt","year":"2017","journal-title":"Haematologica"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1002\/ajh.24532","article-title":"N-Terminal Fragment of the Type-B Natriuretic Peptide (NT-proBNP) Contributes to a Simple New Frailty Score in Patients with Newly Diagnosed Multiple Myeloma","volume":"91","author":"Milani","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41375-019-0539-0","article-title":"A Simplified Frailty Scale Predicts Outcomes in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated in the FIRST (MM-020) Trial","volume":"34","author":"Facon","year":"2020","journal-title":"Leukemia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4621","DOI":"10.1200\/JCO.2009.27.9158","article-title":"Bortezomib plus Dexamethasone Is Superior to Vincristine plus Doxorubicin plus Dexamethasone as Induction Treatment Prior to Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: Results of the IFM 2005-01 Phase III Trial","volume":"28","author":"Harousseau","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1056\/NEJMoa1402551","article-title":"Lenalidomide and Dexamethasone in Transplant-Ineligible Patients with Myeloma","volume":"371","author":"Benboubker","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1038\/leu.2009.147","article-title":"Long-Term Follow-up on Overall Survival from the MM-009 and MM-010 Phase III Trials of Lenalidomide plus Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma","volume":"23","author":"Dimopoulos","year":"2009","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1056\/NEJMoa030288","article-title":"A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma","volume":"348","author":"Richardson","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/leu.2013.313","article-title":"Continued Improvement in Survival in Multiple Myeloma: Changes in Early Mortality and Outcomes in Older Patients","volume":"28","author":"Kumar","year":"2014","journal-title":"Leukemia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/S0140-6736(19)32956-3","article-title":"Overall Survival with Daratumumab, Bortezomib, Melphalan, and Prednisone in Newly Diagnosed Multiple Myeloma (ALCYONE): A Randomised, Open-Label, Phase 3 Trial","volume":"395","author":"Mateos","year":"2020","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1056\/NEJMoa1714678","article-title":"Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma","volume":"378","author":"Mateos","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1056\/NEJMoa1817249","article-title":"Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma","volume":"380","author":"Facon","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1016\/S0140-6736(19)32556-5","article-title":"Isatuximab plus Pomalidomide and Low-Dose Dexamethasone versus Pomalidomide and Low-Dose Dexamethasone in Patients with Relapsed and Refractory Multiple Myeloma (ICARIA-MM): A Randomised, Multicentre, Open-Label, Phase 3 Study","volume":"394","author":"Attal","year":"2019","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/S1470-2045(22)00019-5","article-title":"Isatuximab plus Pomalidomide and Low-Dose Dexamethasone versus Pomalidomide and Low-Dose Dexamethasone in Patients with Relapsed and Refractory Multiple Myeloma (ICARIA-MM): Follow-up Analysis of a Randomised, Phase 3 Study","volume":"23","author":"Richardson","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/S0140-6736(21)00592-4","article-title":"Isatuximab, Carfilzomib, and Dexamethasone in Relapsed Multiple Myeloma (IKEMA): A Multicentre, Open-Label, Randomised Phase 3 Trial","volume":"397","author":"Moreau","year":"2021","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41408-023-00797-8","article-title":"Isatuximab, Carfilzomib, and Dexamethasone in Patients with Relapsed Multiple Myeloma: Updated Results from IKEMA, a Randomized Phase 3 Study","volume":"13","author":"Martin","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1200\/JCO.22.00940","article-title":"Overall Survival with Daratumumab, Lenalidomide, and Dexamethasone in Previously Treated Multiple Myeloma (POLLUX): A Randomized, Open-Label, Phase III Trial","volume":"41","author":"Dimopoulos","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1200\/JCO.21.02734","article-title":"Overall Survival with Daratumumab, Bortezomib, and Dexamethasone in Previously Treated Multiple Myeloma (CASTOR): A Randomized, Open-Label, Phase III Trial","volume":"41","author":"Sonneveld","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1470-2045(21)00579-9","article-title":"Carfilzomib, Dexamethasone, and Daratumumab versus Carfilzomib and Dexamethasone for Patients with Relapsed or Refractory Multiple Myeloma (CANDOR): Updated Outcomes from a Randomised, Multicentre, Open-Label, Phase 3 Study","volume":"23","author":"Usmani","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.clml.2024.07.014","article-title":"Pomalidomide\/Daratumumab\/Dexamethasone in Relapsed or Refractory Multiple Myeloma: Final Overall Survival from MM-014","volume":"24","author":"Bahlis","year":"2024","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S1470-2045(21)00128-5","article-title":"Daratumumab plus Pomalidomide and Dexamethasone versus Pomalidomide and Dexamethasone Alone in Previously Treated Multiple Myeloma (APOLLO): An Open-Label, Randomised, Phase 3 Trial","volume":"22","author":"Dimopoulos","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1038\/s41375-021-01488-8","article-title":"Daratumumab plus Lenalidomide and Dexamethasone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Frailty Subgroup Analysis of MAIA","volume":"36","author":"Facon","year":"2022","journal-title":"Leukemia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.clml.2021.06.005","article-title":"Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Frailty Subgroup Analysis of ALCYONE","volume":"21","author":"Mateos","year":"2021","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"E423","DOI":"10.1002\/ajh.26319","article-title":"Isatuximab plus Pomalidomide and Dexamethasone in Frail Patients with Relapsed\/Refractory Multiple Myeloma: ICARIA-MM Subgroup Analysis","volume":"96","author":"Schjesvold","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1038\/s41591-024-03485-7","article-title":"Daratumumab plus Bortezomib, Lenalidomide and Dexamethasone for Transplant-Ineligible or Transplant-Deferred Newly Diagnosed Multiple Myeloma: The Randomized Phase 3 CEPHEUS Trial","volume":"31","author":"Usmani","year":"2025","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1056\/NEJMoa2400712","article-title":"Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma","volume":"391","author":"Facon","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1056\/NEJMoa2024850","article-title":"Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma","volume":"384","author":"Munshi","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e136","DOI":"10.1002\/hem3.136","article-title":"Long-Term Survival and Safety of Elranatamab in Patients with Relapsed or Refractory Multiple Myeloma: Update from the MagnetisMM-3 Study","volume":"8","author":"Tomasson","year":"2024","journal-title":"Hemasphere"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1056\/NEJMoa2203478","article-title":"Teclistamab in Relapsed or Refractory Multiple Myeloma","volume":"387","author":"Moreau","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1056\/NEJMoa2204591","article-title":"Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma","volume":"387","author":"Chari","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1200\/JCO.2015.61.2267","article-title":"Revised International Staging System for Multiple Myeloma: A Report from International Myeloma Working Group","volume":"33","author":"Palumbo","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5571","DOI":"10.1182\/blood-2019-131114","article-title":"Real World Treatment Patterns and Toxicity Among Elderly Patients with Multiple Myeloma","volume":"134","author":"Heisler","year":"2019","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.3324\/haematol.2017.173617","article-title":"Treat or Palliate: Outcomes of Very Elderly Myeloma Patients","volume":"103","author":"Panitsas","year":"2018","journal-title":"Haematologica"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Huynh, L., Birsen, R., Mora, L., Couderc, A.-L., Mitha, N., Farcet, A., Chebib, A., and Chaibi, P. (2022). Multiple Myeloma in Patients over 80: A Real World Retrospective Study of First Line Conservative Approach with Bortezomib Dexamethasone Doublet Therapy and Mini-Review of Literature. Cancers, 14.","DOI":"10.3390\/cancers14194741"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Tyczy\u0144ska, A., Krzempek, M.K., Cortez, A.J., Jurczyszyn, A., Godlewska, K., Ciep\u0142uch, H., Subocz, E., Ha\u0142ka, J., Kulikowska de Na\u0142\u0119cz, A., and Wi\u015bniewska, A. (2023). The Real-World Evidence on the Fragility and Its Impact on the Choice of Treatment Regimen in Newly Diagnosed Patients with Multiple Myeloma over 75 Years of Age. Cancers, 15.","DOI":"10.20944\/preprints202305.2138.v1"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1080\/10428194.2024.2340052","article-title":"Prevalence of Geriatric Impairments and Frailty Categorization among Real-World Patients with Multiple Myeloma: A Prospective Cohort Study (MFRAIL)","volume":"65","author":"Haider","year":"2024","journal-title":"Leuk. Lymphoma"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6275","DOI":"10.1182\/bloodadvances.2023011019","article-title":"More Intensive Therapy Has a Better Effect for Frail Parents with Multiple Myeloma","volume":"7","author":"DuMontier","year":"2023","journal-title":"Blood Adv."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1182\/bloodadvances.2025015968","article-title":"Clinical Outcomes in Older Adults Treated Outside Clinical Studies: Highlighting the Octogenarian Experience","volume":"9","author":"Shpitzer","year":"2025","journal-title":"Blood Adv."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Palmer, D.B. (2013). The Effect of Age on Thymic Function. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00316"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e13671","DOI":"10.1111\/acel.13671","article-title":"Age-Related Thymic Involution: Mechanisms and Functional Impact","volume":"21","author":"Liang","year":"2022","journal-title":"Aging Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1182\/blood-2015-12-687749","article-title":"Daratumumab Depletes CD38+ Immune Regulatory Cells, Promotes T-Cell Expansion, and Skews T-Cell Repertoire in Multiple Myeloma","volume":"128","author":"Krejcik","year":"2016","journal-title":"Blood"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/7\/1048\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T05:23:10Z","timestamp":1774502590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/7\/1048"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,24]]},"references-count":43,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["cancers18071048"],"URL":"https:\/\/doi.org\/10.3390\/cancers18071048","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,24]]}}}