{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:34:30Z","timestamp":1777354470980,"version":"3.51.4"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019870","name":"Cancer Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019870","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Multiple myeloma (MM) is an incurable malignancy. The treatment mainly includes induction therapy, minimal residual disease (MRD) clearance therapy, and maintenance therapy. For high-risk\/ultra-high-risk (UHR) or relapsed\/refractory MM, optimizing the eradication of MRD and sustaining long-term suppression of MRD at low levels are a formidable challenge. Ixazomib (I) is a reversible proteasome inhibitor (PI) that is available orally as the prodrug ixazomib citrate. Lisaftoclax is a novel, potent, selective BCL-2 inhibitor under clinical development for the treatment of patients with hematologic malignancies or solid tumors and has shown clinical antitumor benefit. Herein, we report two patients with relapsed\/refractory UHR MM who achieved durable disease control with MRD negativity after receiving ixazomib, lisaftoclax, and dexamethasone (ILD) as maintenance therapy following B Cell Maturity Antigen BCMA\u2013chimeric antigen receptor (CAR)-T cell therapy. Regarding the treatment regimen, all drugs were administered orally: ixazomib 4 mg d1, d8, and d15; lisaftoclax 400 mg d1\u2013d14; and dexamethasone 20 mg d1, d8, and d15. One treatment cycle is defined as 28 days. Treatment will be discontinued in the event of uncontrollable active infection or organ injury. These cases demonstrate that the ILD combination therapy can optimize MRD eradication and sustain long-term MRD suppression, offering a promising therapeutic option for patients with limited treatment choices. Formal evaluations of this regimen in patients with high-risk\/ultra-high-risk or relapsed\/refractory MM may be meaningful. This study was supported by the China Cancer Foundation (Project No.: CFC2023WJZD003).<\/jats:p>","DOI":"10.3389\/fonc.2026.1784393","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:34:09Z","timestamp":1777350849000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lisaftoclax combined with ixazomib and dexamethasone after CAR-T for maintenance therapy in transplant-ineligible relapsed\/refractory ultra-high-risk multiple myeloma: two case reports and literature review"],"prefix":"10.3389","volume":"16","author":[{"given":"Weige","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Hematology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]},{"name":"Department of Hematology, The Second Affiliated Hospital of Xingtai Medical College","place":["Xing Tai, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linlin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingnan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaonan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shukai","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022017848","article-title":"Interventions and outcomes of patients with multiple myeloma receiving salvage therapy after BCMA-directed CAR T therapy","volume":"141","author":"Van Oekelen","year":"2023","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.26444\/aaem\/137788","article-title":"Efficacy of ixazomib-lenalidomide-dexamethasone in high-molecular-risk relapsed\/refractory multiple myeloma - case series and literature review","volume":"29","author":"Szudy-Szczyrek","year":"2022","journal-title":"Ann Agric Environ Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-22-3321","article-title":"Novel BCL-2 inhibitor Lisaftoclax in relapsed or refractory chronic lymphocytic leukemia and other hematologic Malignancies: First-in-human open-label trial","volume":"29","author":"Ailawadhi","year":"2023","journal-title":"Clin Cancer Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s40364-025-00803-0","article-title":"Emerging therapeutic agents in multiple myeloma: highlights from the 2024 ASH annual meeting","volume":"13","author":"Zhang","year":"2025","journal-title":"biomark Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2021.1970218","article-title":"Comprehensive meta-analysis of anti-BCMA chimeric antigen receptor T-cell therapy in relapsed or refractory multiple myeloma","volume":"53","author":"Zhang","year":"2021","journal-title":"Ann Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.70012","article-title":"Determinants of 15-year progression-free survival in multiple myeloma; real-world data from a single institution","volume":"100","author":"Dimopoulos","year":"2025","journal-title":"Am J Hematol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000524","article-title":"Long-term outcomes after autologous stem cell transplantation for multiple myeloma","volume":"4","author":"Nishimura","year":"2020","journal-title":"Blood Adv"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02505-2","article-title":"Daratumumab\/lenalidomide\/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes","volume":"39","author":"Facon","year":"2025","journal-title":"Leukemia"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2023.283058","article-title":"Functional cure and long-term survival in multiple myeloma: how to challenge the previously impossible","volume":"109","author":"Engelhardt","year":"2024","journal-title":"Haematologica"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol30020179","article-title":"Relapsed\/refractory multiple myeloma: a review of available therapies and clinical scenarios encountered in myeloma relapse","volume":"30","author":"Bhatt","year":"2023","journal-title":"Curr Oncol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00277-022-05058-5","article-title":"The emerging therapeutic landscape of relapsed\/refractory multiple myeloma","volume":"102","author":"Tanenbaum","year":"2023","journal-title":"Ann Hematol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"36","DOI":"10.46989\/001c.141401","article-title":"Consensus guidelines and recommendations for the anti-CD38-based therapy in clinical practice for relapsed\/refractory multiple myeloma: from the Pan-Pacific Multiple Myeloma Working Group","volume":"7","author":"Chen","year":"2025","journal-title":"Clin Hematol Int"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17172727","article-title":"Safety and efficacy of bispecific antibody treatment in relapsed\/refractory multiple myeloma: a systematic review and meta-analysis of proportions from clinical trials","volume":"17","author":"Bakogeorgou","year":"2025","journal-title":"Cancers (Basel)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3371","DOI":"10.1038\/s41467-024-47801-8","article-title":"Bispecific CAR T cell therapy targeting BCMA and CD19 in relapsed\/refractory multiple myeloma: a phase I\/II trial","volume":"15","author":"Shi","year":"2024","journal-title":"Nat Commun"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2174\/0109298673268932230920063933","article-title":"CAR-T therapy in relapsed refractory multiple myeloma","volume":"31","author":"Ding","year":"2024","journal-title":"Curr Med Chem"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-025-06441-8","article-title":"Ixazomib-lenalidomid-dexamethasone (IRd) in relapsed refractory multiple myeloma (RRMM)-multicenter real-world analysis from Germany and comparative review of the literature","volume":"104","author":"L\u00f6ffler","year":"2025","journal-title":"Ann Hematol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1200\/jco.21.00972","article-title":"Final overall survival analysis of the TOURMALINE-MM1 phase III trial of ixazomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma","volume":"39","author":"Richardson","year":"2021","journal-title":"J Clin Oncol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s13256-020-02376-y","article-title":"Venetoclax in combination with carfilzomib and dexamethasone in relapsed\/refractory multiple myeloma harboring t(11,14)(q13;q32): two case reports and a review of the literature","volume":"14","author":"Abuelgasim","year":"2020","journal-title":"J Med Case Rep"},{"key":"B19","doi-asserted-by":"publisher","first-page":"89","DOI":"10.14740\/jh844","article-title":"Role of Venetoclax in the treatment of relapsed and refractory multiple myeloma","volume":"10","author":"Ehsan","year":"2021","journal-title":"J Hematol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1080\/16078454.2022.2045724","article-title":"Promising therapeutic approaches for relapsed\/refractory multiple myeloma","volume":"27","author":"Ni","year":"2022","journal-title":"Hematology"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(20)30525-8","article-title":"Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial","volume":"21","author":"Kumar","year":"2020","journal-title":"Lancet Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-21-4037","article-title":"Lisaftoclax (APG-2575) is a novel BCL-2 inhibitor with robust antitumor activity in preclinical models of hematologic Malignancy","volume":"28","author":"Deng","year":"2022","journal-title":"Clin Cancer Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/s41423-023-01112-y","article-title":"The BCL-2 inhibitor APG-2575 resets tumor-associated macrophages toward the M1 phenotype, promoting a favorable response to anti-PD-1 therapy via NLRP3 activation","volume":"21","author":"Luo","year":"2024","journal-title":"Cell Mol Immunol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1784393\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:34:18Z","timestamp":1777350858000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1784393\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,28]]},"references-count":23,"alternative-id":["10.3389\/fonc.2026.1784393"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1784393","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,28]]},"article-number":"1784393"}}