{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T23:34:45Z","timestamp":1788564885541,"version":"build-2803163510"},"reference-count":102,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>This review describes the dramatic transformation that has occurred in the last ten years in the therapeutic landscape for hematologic malignancies, such as leukemias, lymphomas, myelomas, and myelodysplastic syndromes. Treatment paradigms have quickly changed from depending solely on cytotoxic chemotherapy to embracing precision medicine, driven by a previously unprecedented understanding of disease biology and precise molecular changes. The development of powerful immunotherapies (such as CAR T-cell therapy and bispecific antibodies) and innovative targeted agents (like BTK inhibitors, BCL-2 inhibitors, and immunomodulatory medications) is at the heart of this revolution. In addition to evaluating new and synergistic combination strategies, this paper examines the clinical utility, efficacy, and recent developments of these novel agents. It also addresses important issues like managing acquired drug resistance, minimizing financial burden, and adapting clinical trial designs to keep pace with innovation. These advancements are collectively redefining clinical practice, leading to deeper and more durable responses, and significantly improving the prognosis and quality of life for patients.<\/jats:p>","DOI":"10.3390\/jcm14248896","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T14:36:53Z","timestamp":1765895813000},"page":"8896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Precision Revolution in Hematologic Malignancies: A Decade of Transformative Immunotherapies and Targeted Agents"],"prefix":"10.3390","volume":"14","author":[{"given":"Ghaith K.","family":"Mansour","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0024-3751","authenticated-orcid":false,"given":"Ahmad W.","family":"Hajjar","sequence":"additional","affiliation":[{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6082-3928","authenticated-orcid":false,"given":"Muhammad Raihan","family":"Sajid","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kaye, D., and Isidori, A. (2021). Current Challenges in Hematology: Awareness, Prevention, Equity. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.653020"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"595","DOI":"10.21037\/atm.2019.05.58","article-title":"Immunotherapy and Targeted Therapy-the New Roadmap in Cancer Treatment","volume":"7","author":"Shahid","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"oyae331","DOI":"10.1093\/oncolo\/oyae331","article-title":"Reinventing Chemotherapy","volume":"30","author":"Chabner","year":"2025","journal-title":"Oncologist"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7638","DOI":"10.1182\/blood-2024-208782","article-title":"Evaluating Recent Drug Approvals for Hematologic Malignancies Utilizing the New European Society of Medical Oncology Magnitude of Clinical Benefit Scale for Hematology (ESMO-MCBS:H)","volume":"144","author":"Hirsh","year":"2024","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7765","DOI":"10.1182\/blood-2024-210267","article-title":"Regulatory Considerations for Approval of Chimeric Antigen Receptor T Cell Therapies for Treatment of Hematological Malignancies","volume":"144","author":"Elmacken","year":"2024","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"20406207221116577","DOI":"10.1177\/20406207221116577","article-title":"Selecting the Optimal BTK Inhibitor Therapy in CLL: Rationale and Practical Considerations","volume":"13","author":"Lovell","year":"2022","journal-title":"Ther. Adv. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3832","DOI":"10.3324\/haematol.2024.286233","article-title":"Therapy for Acute Myeloid Leukemia in Older and Unfit Adults","volume":"109","author":"Forsberg","year":"2024","journal-title":"Haematologica"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bangolo, A., Amoozgar, B., Mansour, C., Zhang, L., Gill, S., Ip, A., and Cho, C. (2025). Comprehensive Review of Early and Late Toxicities in CAR T-Cell Therapy and Bispecific Antibody Treatments for Hematologic Malignancies. Cancers, 17.","DOI":"10.3390\/cancers17020282"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1182\/blood.2022018730","article-title":"Lisocabtagene Maraleucel as Second-Line Therapy for Large B-Cell Lymphoma: Primary Analysis of the Phase 3 TRANSFORM Study","volume":"141","author":"Abramson","year":"2023","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Khan, S.H., Choi, Y., Veena, M., Lee, J.K., and Shin, D.S. (2024). Advances in CAR T Cell Therapy: Antigen Selection, Modifications, and Current Trials for Solid Tumors. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1489827"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/0115665232357078250331180413","article-title":"CRISPR\/Cas9 Technology for Modifying Immune Checkpoint in CAR-T Cell Therapy for Hematopoietic Malignancies","volume":"25","author":"Shams","year":"2025","journal-title":"Curr. Gene Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1182\/blood-2024-199723","article-title":"Real-World (RW) Outcomes of Lisocabtagene Maraleucel (Liso-Cel) as Second-Line (2L) Therapy in Patients (Pts) with Relapsed or Refractory (R\/R) Large B-Cell Lymphoma (LBCL): First Results from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry","volume":"144","author":"Bobillo","year":"2024","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Caimi, P.F., Pacheco Sanchez, G., Sharma, A., Otegbeye, F., Ahmed, N., Rojas, P., Patel, S., Kleinsorge Block, S., Schiavone, J., and Zamborsky, K. (2021). Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.745320"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.1182\/bloodadvances.2023012221","article-title":"BTK Inhibitors in CLL: Second-Generation Drugs and Beyond","volume":"8","author":"Tam","year":"2024","journal-title":"Blood Adv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1002\/hon.3164_341","article-title":"Zanubrutinib versus Ibrutinib in Relapsed\/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (R\/R CLL\/SLL): Impact on Health-related Quality of Life","volume":"41","author":"Eichhorst","year":"2023","journal-title":"Hematol. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ahn, I.E., and Brown, J.R. (2021). Targeting Bruton\u2019s Tyrosine Kinase in CLL. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.687458"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Frustaci, A.M., Deodato, M., Zamprogna, G., Cairoli, R., Montillo, M., and Tedeschi, A. (2023). Next Generation BTK Inhibitors in CLL: Evolving Challenges and New Opportunities. Cancers, 15.","DOI":"10.3390\/cancers15051504"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1182\/hematology.2022000344","article-title":"Novel Therapies and Combinations in CLL Refractory to BTK Inhibitors and Venetoclax","volume":"2022","year":"2022","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5833","DOI":"10.1182\/blood-2024-202909","article-title":"Bgb-16673, a Selective BTK Degrader, Exhibits Deeper Inhibition of Cancer Cell Signaling Pathways and Better Efficacy in MCL Models","volume":"144","author":"Wang","year":"2024","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1200\/JCO.23.01911","article-title":"Azacitidine, Venetoclax, and Gilteritinib in Newly Diagnosed and Relapsed or Refractory FLT3-Mutated AML","volume":"42","author":"Short","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1158\/2643-3230.BCD-22-0205","article-title":"A Phase Ib\/II Study of Ivosidenib with Venetoclax \u00b1 Azacitidine in IDH1-Mutated Myeloid Malignancies","volume":"4","author":"Lachowiez","year":"2023","journal-title":"Blood Cancer Discov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1080\/1120009X.2023.2247200","article-title":"Comparison of Venetoclax and Ivosidenib\/Enasidenib for Unfit Newly Diagnosed Patients with Acute Myeloid Leukemia and IDH1\/2 Mutation: A Network Meta-Analysis","volume":"36","author":"Wang","year":"2024","journal-title":"J. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s40259-025-00735-z","article-title":"Bispecific Antibodies in Hematologic Malignancies: Attacking the Frontline","volume":"39","author":"Shastri","year":"2025","journal-title":"BioDrugs"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tacchetti, P., Barbato, S., Mancuso, K., Zamagni, E., and Cavo, M. (2024). Bispecific Antibodies for the Management of Relapsed\/Refractory Multiple Myeloma. Cancers, 16.","DOI":"10.3390\/cancers16132337"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1158\/2643-3230.BCD-23-0176","article-title":"An Embarrassment of Riches: Three FDA-Approved Bispecific Antibodies for Relapsed Refractory Multiple Myeloma","volume":"4","author":"Firestone","year":"2023","journal-title":"Blood Cancer Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1158\/2643-3230.BCD-24-0354","article-title":"Real-World Experience with Teclistamab for Relapsed\/Refractory Multiple Myeloma from the US Myeloma Immunotherapy Consortium","volume":"6","author":"Razzo","year":"2025","journal-title":"Blood Cancer Discov."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Rees, M., Abdallah, N., Yohannan, B., and Gonsalves, W.I. (2024). Bispecific Antibody Targets and Therapies in Multiple Myeloma. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1424925"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1158\/1078-0432.CCR-23-3333","article-title":"T-Cell Characteristics Impact Response and Resistance to T-Cell-Redirecting Bispecific Antibodies in Multiple Myeloma","volume":"30","author":"Verkleij","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1182\/blood.2024026932","article-title":"BCMA Bispecifics: Breaking the Chains of Resistance","volume":"144","author":"Waldschmidt","year":"2024","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3390\/hematolrep16020024","article-title":"A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia","volume":"16","author":"Candoni","year":"2024","journal-title":"Hematol. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1200\/JCO.24.00826","article-title":"Menin Inhibition with Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101)","volume":"43","author":"Issa","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13045-023-01411-x","article-title":"Novel Agents and Regimens in Acute Myeloid Leukemia: Latest Updates from 2022 ASH Annual Meeting","volume":"16","author":"DiNardo","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Adriaanse, F.R.S., Schneider, P., Arentsen-Peters, S.T.C.J.M., da Fonseca, A.M.N., Stutterheim, J., Pieters, R., Zwaan, C.M., and Stam, R.W. (2024). Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116020"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/bjh.19519","article-title":"Combination Therapy with Novel Agents for Acute Myeloid Leukaemia: Insights into Treatment of a Heterogenous Disease","volume":"205","author":"Jen","year":"2024","journal-title":"Br. J. Haematol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1158\/1078-0432.CCR-21-3405","article-title":"Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Na\u00efve Acute Myeloid Leukemia","volume":"28","author":"Konopleva","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1056\/NEJMoa1614359","article-title":"Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation","volume":"377","author":"Stone","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1056\/NEJMoa1902688","article-title":"Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML","volume":"381","author":"Perl","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Cerchione, C., Romano, A., Daver, N., DiNardo, C., Jabbour, E.J., Konopleva, M., Ravandi-Kashani, F., Kadia, T., Martelli, M.P., and Isidori, A. (2021). IDH1\/IDH2 Inhibition in Acute Myeloid Leukemia. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.639387"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1182\/blood-2021-146507","article-title":"Updated Survival and Response Analyses from a Phase 1 Study of Ivosidenib or Enasidenib Combined with Induction and Consolidation Chemotherapy in Patients with Newly Diagnosed AML with an IDH1 or IDH2 Mutation","volume":"138","author":"Stein","year":"2021","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1158\/2159-8290.CD-18-0140","article-title":"A Novel MCL1 Inhibitor Combined with Venetoclax Rescues Venetoclax-Resistant Acute Myelogenous Leukemia","volume":"8","author":"Ramsey","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1182\/blood.2022017341","article-title":"Mechanisms of Resistance to Venetoclax","volume":"140","author":"Condoluci","year":"2022","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ejca.2016.06.009","article-title":"Next-generation personalised medicine for high-risk paediatric cancer patients\u2014The INFORM pilot study","volume":"65","author":"Worst","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1158\/2159-8290.CD-16-1396","article-title":"High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial","volume":"7","author":"Massard","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40364-022-00357-5","article-title":"Combining BTK Inhibitors with BCL2 Inhibitors for Treating Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma","volume":"10","author":"Zhang","year":"2022","journal-title":"Biomark. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/S1470-2045(20)30443-5","article-title":"Venetoclax plus Obinutuzumab versus Chlorambucil plus Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukaemia (CLL14): Follow-up Results from a Multicentre, Open-Label, Randomised, Phase 3 Trial","volume":"21","author":"Zhang","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3278","DOI":"10.1182\/blood.2021014488","article-title":"Fixed-Duration Ibrutinib plus Venetoclax for First-Line Treatment of CLL: Primary Analysis of the CAPTIVATE FD Cohort","volume":"139","author":"Tam","year":"2022","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6101","DOI":"10.1158\/1078-0432.CCR-17-0381","article-title":"Molecular Screening for Cancer Treatment Optimization (MOSCATO-01) in Pediatric Patients: A Single-Institutional Prospective Molecular Stratification Trial","volume":"23","author":"Harttrampf","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_48","first-page":"3059","article-title":"IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin\u2019s lymphoma","volume":"89","author":"Maloney","year":"1997","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1056\/NEJMoa011795","article-title":"CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma","volume":"346","author":"Coiffier","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1056\/NEJMe2118899","article-title":"Chimeric Antigen Receptor T-Cell Therapy for Large B-Cell Lymphoma: Who, When, and How?","volume":"386","author":"Roschewski","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_51","first-page":"2277","article-title":"Brentuximab Vedotin for Treatment of Relapsed or Refractory Malignant Lymphoma: Results of a Systematic Review and Meta-Analysis of Prospective Studies","volume":"9","author":"Chen","year":"2015","journal-title":"Drug Des. Devel Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1182\/bloodadvances.2021005794","article-title":"Polatuzumab Vedotin plus Bendamustine and Rituximab in Relapsed\/Refractory DLBCL: Survival Update and New Extension Cohort Data","volume":"6","author":"Sehn","year":"2022","journal-title":"Blood Adv."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41591-018-0016-8","article-title":"Molecular Subtypes of Diffuse Large B Cell Lymphoma Are Associated with Distinct Pathogenic Mechanisms and Outcomes","volume":"24","author":"Chapuy","year":"2018","journal-title":"Nat. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1053\/j.seminhematol.2024.12.001","article-title":"Advancements in Bispecific Antibodies for Multiple Myeloma: What\u2019s New and What Lies Ahead","volume":"62","author":"Mouhieddine","year":"2025","journal-title":"Semin. Hematol."},{"key":"ref_55","doi-asserted-by":"crossref","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":"ref_56","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s13045-023-01489-3","article-title":"Bispecific Antibodies Targeting BCMA, GPRC5D, and FcRH5 for Multiple Myeloma Therapy: Latest Updates from ASCO 2023 Annual Meeting","volume":"16","author":"Zhao","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1056\/NEJMoa2209900","article-title":"GPRC5D-Targeted CAR T Cells for Myeloma","volume":"387","author":"Mailankody","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1056\/NEJMoa1609783","article-title":"Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia","volume":"376","author":"Kantarjian","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1056\/NEJMoa1509277","article-title":"Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia","volume":"375","author":"Kantarjian","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/S1470-2045(14)70243-8","article-title":"Augmented post-remission therapy for a minimal residual disease-defined high-risk subgroup of children and young people with clinical standard-risk and intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): A randomised controlled phase 3 trial","volume":"15","author":"Vora","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s40364-024-00589-7","article-title":"The CDK9 Inhibitor Enitociclib Overcomes Resistance to BTK Inhibition and CAR-T Therapy in Mantle Cell Lymphoma","volume":"12","author":"Jiang","year":"2024","journal-title":"Biomark. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1182\/blood.2020006783","article-title":"Resistance to Bruton Tyrosine Kinase Inhibitors: The Achilles Heel of Their Success Story in Lymphoid Malignancies","volume":"138","author":"Stephens","year":"2021","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1056\/NEJMoa2114110","article-title":"Mechanisms of Resistance to Noncovalent Bruton\u2019s Tyrosine Kinase Inhibitors","volume":"386","author":"Wang","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_64","first-page":"372","article-title":"Mechanisms of Resistance to CAR T Cell Therapy","volume":"16","author":"Shah","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Legato, L., Bisio, M., Fasano, F., Benevolo Savelli, C., Secreto, C., Dellacasa, C.M., Botto, B., Busca, A., Cerrano, M., and Freilone, R. (2025). Mechanisms of Resistance to CAR T-Cells and How to Overcome Them. Methods Protoc., 8.","DOI":"10.3390\/mps8050108"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"El Achi, H., and Kanagal-Shamanna, R. (2021). Biomarkers in Acute Myeloid Leukemia: Leveraging Next Generation Sequencing Data for Optimal Therapeutic Strategies. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.748250"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e390010","DOI":"10.1200\/EDBK_390010","article-title":"Using Measurable Residual Disease to Optimize Management of AML, ALL, and Chronic Myeloid Leukemia","volume":"43","author":"Dekker","year":"2023","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1182\/blood-2024-199813","article-title":"Circulating Tumor DNA (ctDNA) as an Early Outcome Predictor in Patients (Pts) with Second-Line (2L) Large B-Cell Lymphoma (LBCL) after Lisocabtagene Maraleucel (Liso-Cel) Versus Standard of Care (SOC) Treatment (Tx) from the Phase 3, Randomized Transform Study","volume":"144","author":"Stepan","year":"2024","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e981","DOI":"10.1097\/HS9.0000000000000981","article-title":"Prognostic Significance of Measurable Residual Disease Detection by Flow Cytometry in Autologous Stem Cell Apheresis Products in AML","volume":"7","author":"Tettero","year":"2023","journal-title":"Hemasphere"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"J\u00f3na, \u00c1., and Ill\u00e9s, \u00c1. (2025). Sequencing Cellular Therapies in the Management of Follicular Lymphoma. Cells, 14.","DOI":"10.3390\/cells14211671"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s11899-023-00700-z","article-title":"Relapsed\/Refractory Chronic Lymphocytic Leukemia (CLL)","volume":"18","author":"Odetola","year":"2023","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5516","DOI":"10.1182\/bloodadvances.2022007938","article-title":"International Consensus Statement on the Management of Cardiovascular Risk of Bruton\u2019s Tyrosine Kinase Inhibitors in CLL","volume":"6","author":"Awan","year":"2022","journal-title":"Blood Adv."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Mela, E., and Frountzas, M. (2025). Gastrointestinal Cancer: Outcomes and Therapeutic Management. J. Clin. Med., 14.","DOI":"10.3390\/jcm14217541"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Kamau, B., Shulimovich, M., and Samridhi, S. (2025). The Impact of Novel Therapies on Quality-of-Life in Triple-Negative Breast Cancer: A Systematic Review of Clinical Trials. Cancers, 17.","DOI":"10.3390\/cancers17203307"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4324","DOI":"10.1182\/blood-2024-211178","article-title":"Outcomes and Survival in Newly Diagnosed, Older, Acute Myeloid Leukemia Patients from the Beat AML Master Trial in the Venetoclax\/Azacitidine Age","volume":"144","author":"Borate","year":"2024","journal-title":"Blood"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"a001370","DOI":"10.1101\/mcs.a001370","article-title":"Integrating Functional Genomics to Accelerate Mechanistic Personalized Medicine","volume":"3","author":"Tyner","year":"2017","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"103798","DOI":"10.1016\/j.isci.2022.103798","article-title":"Machine Learning for Multi-Omics Data Integration in Cancer","volume":"25","author":"Cai","year":"2022","journal-title":"iScience"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1158\/1541-7786.MCR-21-0255","article-title":"A Functional Precision Oncology Approach to Identify Treatment Strategies for Myxofibrosarcoma Patients","volume":"20","author":"Pauli","year":"2022","journal-title":"Mol. Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1158\/0008-5472.CAN-22-3015","article-title":"Epigenetic-Metabolic Interplay in the DNA Damage Response and Therapeutic Resistance of Breast Cancer","volume":"83","author":"Das","year":"2023","journal-title":"Cancer Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e165694","DOI":"10.1172\/JCI165694","article-title":"Cotargeting of BTK and MALT1 Overcomes Resistance to BTK Inhibitors in Mantle Cell Lymphoma","volume":"133","author":"Jiang","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Zhang, M., Lam, K.-P., and Xu, S. (2023). Natural Killer Cell Engagers (NKCEs): A New Frontier in Cancer Immunotherapy. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1207276"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"In, H., Park, M., Lee, H., and Han, K.H. (2025). Immune Cell Engagers: Advancing Precision Immunotherapy for Cancer Treatment. Antibodies, 14.","DOI":"10.3390\/antib14010016"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1080\/21645515.2019.1571893","article-title":"CRISPR\/Cas9-Based Genome Editing in the Era of CAR T Cell Immunotherapy","volume":"15","author":"Kong","year":"2019","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Elmas, E., Saljoughian, N., de Souza Fernandes Pereira, M., Tullius, B.P., Sorathia, K., Nakkula, R.J., Lee, D.A., and Naeimi Kararoudi, M. (2022). CRISPR Gene Editing of Human Primary NK and T Cells for Cancer Immunotherapy. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.834002"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Hu, C., Lai, W., Tian, B., Xu, X., Xie, S., Zhong, W., Kang, H., Chen, X., Li, H., and Xu, J. (2025). Application and Prospects of Genetic Engineering in CAR-NK Cell Therapy. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1600411"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7578","DOI":"10.1182\/blood-2024-206129","article-title":"Financial Toxicity of FDA-Approved Hematologic Malignancy Drugs: An Epidemiological Analysis of Cost","volume":"144","author":"Weeks","year":"2024","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"200980","DOI":"10.1016\/j.omton.2025.200980","article-title":"Cost-Effective Strategies for CAR-T Cell Therapy Manufacturing","volume":"33","author":"Abdo","year":"2025","journal-title":"Mol. Ther. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"lsae030","DOI":"10.1093\/jlb\/lsae030","article-title":"Accelerating Biosimilar Market Access: The Case for Allowing Earlier Standing","volume":"12","author":"Tu","year":"2025","journal-title":"J. Law. Biosci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1377\/hlthaff.2010.1147","article-title":"Risk-Sharing Arrangements That Link Payment for Drugs to Health Outcomes Are Proving Hard to Implement","volume":"30","author":"Neumann","year":"2011","journal-title":"Health Aff."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1016\/j.ymthe.2021.05.024","article-title":"Collaborative Science to Advance Gene Therapies in Resource-Limited Parts of the World","volume":"29","author":"McCune","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1093\/cid\/cix907","article-title":"Adaptive Designs for Clinical Trials: Application to Healthcare Epidemiology Research","volume":"66","author":"Huskins","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"405","DOI":"10.21037\/jgo.2016.11.15","article-title":"Predictive and Prognostic Biomarkers in Personalized Gastrointestinal Cancer Treatment","volume":"8","author":"Verdaguer","year":"2017","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1158\/2643-3230.BCD-23-0067","article-title":"Synergistic Drug Combinations Promote the Development of Resistance in Acute Myeloid Leukemia","volume":"5","author":"Pomeroy","year":"2024","journal-title":"Blood Cancer Discov."},{"key":"ref_94","first-page":"1208","article-title":"Next-Generation CAR-T: In Vivo Engineering with Lipid Nanoparticles","volume":"5","author":"Siddiqui","year":"2025","journal-title":"J. Clin. Med. Surg."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e55918","DOI":"10.2196\/55918","article-title":"Telemedicine with Wearable Technologies in Patients Undergoing Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapy (TEL-HEMATO Study): Prospective Noninterventional Single-Center Study","volume":"8","author":"Hurtado","year":"2024","journal-title":"JMIR Form. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/clinchem\/hvad196","article-title":"Looking to the Future of Early Detection in Cancer: Liquid Biopsies, Imaging, and Artificial Intelligence","volume":"70","author":"Foser","year":"2024","journal-title":"Clin. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Reis, M.E., Bettencourt, A., and Ribeiro, H.M. (2022). The Regulatory Challenges of Innovative Customized Combination Products. Front. Med., 9.","DOI":"10.3389\/fmed.2022.821094"},{"key":"ref_98","first-page":"49","article-title":"Adaptive Clinical Trial Designs in Oncology","volume":"3","author":"Zang","year":"2014","journal-title":"Chin. Clin. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e23010","DOI":"10.1200\/JCO.2025.43.16_suppl.e23010","article-title":"Master Protocols in Oncology: Opportunities, Challenges, and Strategic Approaches to Design and Implementation","volume":"43","author":"Confeld","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e70117","DOI":"10.1002\/pds.70117","article-title":"Real-World Data and Real-World Evidence in Regulatory Decision Making: Report Summary from the Council for International Organizations of Medical Sciences (CIOMS) Working Group XIII","volume":"34","author":"Hennessy","year":"2025","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s40264-017-0526-1","article-title":"Evaluation of Pre-Marketing Factors to Predict Post-Marketing Boxed Warnings and Safety Withdrawals","volume":"40","author":"Schick","year":"2017","journal-title":"Drug Saf."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.32628\/CSEIT251112118","article-title":"Regulatory Harmonization: Streamlining Global Pharmaceutical Validation Practices","volume":"11","author":"Rajpuriya","year":"2025","journal-title":"Int. J. Sci. Res. Comput. Sci. Eng. Inf. Technol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/24\/8896\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T05:34:28Z","timestamp":1766036068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/24\/8896"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,16]]},"references-count":102,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["jcm14248896"],"URL":"https:\/\/doi.org\/10.3390\/jcm14248896","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,16]]}}}