{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:42:07Z","timestamp":1766050927731,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Follicular lymphoma management is rapidly evolving with advanced cellular therapies. This review examines the optimal sequencing of autologous stem cell transplantation (autoSCT), allogeneic stem cell transplantation (alloSCT), and CAR T-cell therapy. AutoSCT is a crucial intervention for chemosensitive relapsed FL, prolonging progression-free survival, though not typically curative. AlloSCT, offering a potential cure via a graft-versus-lymphoma effect, carries significant risks like graft-versus-host disease and non-relapse mortality, thus primarily serving as a salvage option for high-risk or treatment-refractory cases after other modalities, including autoSCT. CAR T-cell therapy, utilizing genetically modified T cells targeting CD19, has revolutionized relapsed\/refractory FL. Products like axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel have demonstrated high response rates and durable remissions even in heavily pretreated patients with high-risk features. This potent therapy is increasingly considered a bridge between autoSCT and alloSCT, expanding treatment options. Additionally, bispecific antibodies such as mosunetuzumab, epcoritamab and odrenextamab provide convenient off-the-shelf options, exhibiting strong efficacy and favorable safety. However, their impact on subsequent CAR-T outcomes, especially with CD19-targeting bispecifics, remains an area of ongoing investigation and uncertainty. The complex interplay of these therapies necessitates individualized decisions, emphasizing patient characteristics and disease-specific factors to optimize outcomes in FL. Further research into predictive biomarkers and refined treatment algorithms is crucial for future management.<\/jats:p>","DOI":"10.3390\/cells14211671","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T02:50:48Z","timestamp":1761533448000},"page":"1671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sequencing Cellular Therapies in the Management of Follicular Lymphoma"],"prefix":"10.3390","volume":"14","author":[{"given":"\u00c1d\u00e1m","family":"J\u00f3na","sequence":"first","affiliation":[{"name":"Department of Hematology, Faculty of Medicine, University of Debrecen, Member of the ERN-EuroBloodNet (European Reference Network on Rare Haematological Diseases), H-4032 Debrecen, Hungary"},{"name":"Doctoral School of Clinical Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1rp\u00e1d","family":"Ill\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Hematology, Faculty of Medicine, University of Debrecen, Member of the ERN-EuroBloodNet (European Reference Network on Rare Haematological Diseases), H-4032 Debrecen, Hungary"},{"name":"Doctoral School of Clinical Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Clemente, M.B., Collazo-Lorduy, A., Yanguas-Cas\u00e1s, N., Calvo, V., and Provencio, M. (2022). Unveiling the Role of the Tumor Microenvironment in the Treatment of Follicular Lymphoma. Cancers, 14.","DOI":"10.3390\/cancers14092158"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1080\/17474086.2017.1326812","article-title":"Follicular Lymphomas and Their Transformation: Past and Current Research","volume":"10","author":"Torrente","year":"2017","journal-title":"Expert Rev. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.beha.2011.02.006","article-title":"Transformation of Follicular Lymphoma","volume":"24","author":"Lossos","year":"2011","journal-title":"Best Pract. Res. Clin. Haematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3960\/jslrt.22046","article-title":"Histologic Transformation of Follicular Lymphoma: Pathologists\u2019 Viewpoint","volume":"63","author":"Maeshima","year":"2023","journal-title":"J. Clin. Exp. Hematop."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e70070","DOI":"10.1002\/hon.70070","article-title":"Follicular Lymphoma: Current Therapeutic Landscape and Future Prospects","volume":"43","author":"Kumar","year":"2025","journal-title":"Hematol. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1111\/ejh.14401","article-title":"Relapsed\/Refractory Follicular Lymphoma: Current Advances and Emerging Perspectives","volume":"114","author":"Martino","year":"2025","journal-title":"Eur. J. Haematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/ejh.14335","article-title":"Comparative Analysis of Bispecific Antibodies and CAR T-Cell Therapy in Follicular Lymphoma","volume":"114","author":"Morabito","year":"2024","journal-title":"Eur. J. Haematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1182\/hematology.2024000667","article-title":"Sequencing Bispecific Antibodies and CAR T Cells for FL","volume":"2024","author":"Bartlett","year":"2024","journal-title":"Hematology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"257","DOI":"10.2147\/CMAR.S381493","article-title":"Targeted Treatment of Relapsed or Refractory Follicular Lymphoma: Focus on the Therapeutic Potential of Mosunetuzumab","volume":"15","author":"Lopedote","year":"2023","journal-title":"Cancer Manag. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1182\/hematology.2020000156","article-title":"How Do I Sequence Therapy for Follicular Lymphoma?","volume":"2020","author":"Salles","year":"2020","journal-title":"Hematology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.jtct.2024.06.025","article-title":"Clinical Practice Recommendations for Hematopoietic Cell Transplantation and Cellular Therapies in Follicular Lymphoma: A Collaborative Effort on Behalf of the American Society for Transplantation and Cellular Therapy and the European Society for Blood and Marrow Transplantation","volume":"30","author":"Iqbal","year":"2024","journal-title":"Transplant. Cell. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tomblyn, M., Ewell, M., Bredeson, C., Kahl, B.S., Goodman, S., Horowitz, M.M., Vose, J.M., Negrin, R.S., and Laport, G.G. (2010). Autologous versus Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Patients with Chemosensitive Follicular Non-Hodgkin Lymphoma beyond First Complete Response or First Partial Response. Biol. Blood Marrow Transplant., 17.","DOI":"10.1016\/j.bbmt.2010.11.004"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Jurinovi\u0107, V., Metzner, B., Pfreundschuh, M., Schmitz, N., Wandt, H., Keller, U., Dreger, P., Dreyling, M., Hiddemann, W., and Unterhalt, M. (2018). Autologous Stem Cell Transplantation for Patients with Early Progression of Follicular Lymphoma: A Follow-Up Study of 2 Randomized Trials from the German Low Grade Lymphoma Study Group. Biol. Blood Marrow Transplant., 24.","DOI":"10.1016\/j.bbmt.2018.03.022"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Casulo, C., Friedberg, J.W., Ahn, K.W., Flowers, C.R., DiGilio, A., Smith, S.M., Ahmed, S., Inwards, D.J., Aljurf, M., and Chen, A.I. (2017). Autologous Transplantation in Follicular Lymphoma with Early Therapy Failure: A National LymphoCare Study and Center for International Blood and Marrow Transplant Research Analysis. Biol. Blood Marrow Transplant., 24.","DOI":"10.1016\/j.bbmt.2017.12.771"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1182\/blood-2018-08-822148","article-title":"How I Treat Early-Relapsing Follicular Lymphoma","volume":"133","author":"Casulo","year":"2019","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s40487-021-00161-5","article-title":"Early Relapse in First-Line Follicular Lymphoma: A Review of the Clinical Implications and Available Mitigation and Management Strategies","volume":"9","author":"Rodgers","year":"2021","journal-title":"Oncol. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"03000605231221012","DOI":"10.1177\/03000605231221012","article-title":"Age and Lymphocyte\/Monocyte Ratio as Prognostic Factors for Autologous Transplantation in the Treatment of Patients with Follicular Lymphoma","volume":"52","author":"Kenyeres","year":"2024","journal-title":"J. Int. Med. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1093\/annonc\/mdw124","article-title":"Reduced Intensity Allogeneic Stem Cell Transplantation for Follicular Lymphoma Relapsing after an Autologous Transplant Achieves Durable Long-Term Disease Control: An Analysis from the Lymphoma Working Party of the EBMT","volume":"27","author":"Robinson","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.hoc.2020.02.006","article-title":"Cellular Therapy in Follicular Lymphoma: Autologous Stem Cell Transplantation, Allogeneic Stem Cell Transplantation, and Chimeric Antigen Receptor T-Cell Therapy","volume":"34","author":"Lenz","year":"2020","journal-title":"Hematol.\/Oncol. Clin."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1038\/bmt.2013.83","article-title":"The Outcome of Reduced Intensity Allogeneic Stem Cell Transplantation and Autologous Stem Cell Transplantation When Performed as a First Transplant Strategy in Relapsed Follicular Lymphoma: An Analysis from the Lymphoma Working Party of the EBMT","volume":"48","author":"Robinson","year":"2013","journal-title":"Bone Marrow Transplant."},{"key":"ref_21","unstructured":"(2020). Stem Cells and Cloning: Advances and Applications. Stem Cells Cloning Adv. Appl."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/s41409-022-01691-w","article-title":"Indications for Haematopoietic Cell Transplantation for Haematological Diseases, Solid Tumours and Immune Disorders: Current Practice in Europe, 2022","volume":"57","author":"Snowden","year":"2022","journal-title":"Bone Marrow Transplant."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s40164-024-00551-1","article-title":"Current and Future Therapies for Follicular Lymphoma","volume":"13","author":"Zinzani","year":"2024","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e593","DOI":"10.1016\/S2352-3026(24)00166-2","article-title":"Epcoritamab Monotherapy in Patients with Relapsed or Refractory Follicular Lymphoma (EPCORE NHL-1): A Phase 2 Cohort of a Single-Arm, Multicentre Study","volume":"11","author":"Linton","year":"2024","journal-title":"Lancet Haematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1182\/blood.2023021243","article-title":"Three-Year Follow-up Analysis of Axicabtagene Ciloleucel in Relapsed\/Refractory Indolent Non-Hodgkin Lymphoma (ZUMA-5)","volume":"143","author":"Neelapu","year":"2023","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1182\/blood.2023021567","article-title":"Durable Response after Tisagenlecleucel in Adults with Relapsed\/Refractory Follicular Lymphoma: ELARA Trial Update","volume":"143","author":"Dreyling","year":"2024","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1038\/s41591-024-02986-9","article-title":"Lisocabtagene Maraleucel in Follicular Lymphoma: The Phase 2 TRANSCEND FL Study","volume":"30","author":"Morschhauser","year":"2024","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s40164-025-00610-1","article-title":"Matching-Adjusted Indirect Comparison of Efficacy and Safety of Lisocabtagene Maraleucel and Mosunetuzumab for the Treatment of Third-Line or Later Relapsed or Refractory Follicular Lymphoma","volume":"14","author":"Nastoupil","year":"2025","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/S1470-2045(22)00335-7","article-title":"Safety and Efficacy of Mosunetuzumab, a Bispecific Antibody, in Patients with Relapsed or Refractory Follicular Lymphoma: A Single-Arm, Multicentre, Phase 2 Study","volume":"23","author":"Budde","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1182\/blood.2024025454","article-title":"Long-Term 3-Year Follow-up of Mosunetuzumab in Relapsed or Refractory Follicular Lymphoma after \u22652 Prior Therapies","volume":"145","author":"Sehn","year":"2024","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e240_70094","DOI":"10.1002\/hon.70094_240","article-title":"Epcoritamab Monotherapy Demonstrates Deep and Durable Responses at 3-Year Follow-Up in Patients with Relapsed\/Refractory Follicular Lymphoma","volume":"43","author":"Linton","year":"2025","journal-title":"Hematol. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.annonc.2024.08.2239","article-title":"Safety and Efficacy of Odronextamab in Patients with Relapsed or Refractory Follicular Lymphoma","volume":"35","author":"Kim","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3754","DOI":"10.1182\/bloodadvances.2024015274","article-title":"Indirect Comparison of Epcoritamab vs Chemoimmunotherapy, Mosunetuzumab, or Odronextamab in Follicular Lymphoma","volume":"9","author":"Danilov","year":"2025","journal-title":"Blood Adv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1182\/blood-2023-178786","article-title":"Matching-Adjusted Indirect Comparison (MAIC) of Effcacy and Safety of Lisocabtagene Maraleucel (Liso-Cel) and Mosunetuzumab for the Treatment (Tx) of Third Line or Later (3L+) Relapsed or Refractory (R\/R) Follicular Lymphoma (FL)","volume":"142","author":"Nastoupil","year":"2023","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"885-e1","DOI":"10.1016\/j.jtct.2024.06.016","article-title":"Matching-Adjusted Indirect Comparisons of Axicabtagene Ciloleucel to Mosunetuzumab for the Treatment of Relapsed\/Refractory Follicular Lymphoma","volume":"30","author":"Ray","year":"2024","journal-title":"Transplant. Cell. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5082","DOI":"10.1182\/blood-2023-186548","article-title":"Cost-Effectiveness of Axicabtagene Ciloleucel Versus Mosunetuzumab in Relapsed\/Refractory Follicular Lymphoma in the US","volume":"142","author":"Oluwole","year":"2023","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Sun, L., and Romancik, J.T. (2025). The Development and Application of Bispecific Antibodies in B-Cell Non-Hodgkin Lymphoma. J. Pers. Med., 15.","DOI":"10.3390\/jpm15020051"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Omer, M.H., Shafqat, A., Ahmad, O., Alkattan, K., Yaqinuddin, A., and Damlaj, M. (2023). Bispecific Antibodies in Hematological Malignancies: A Scoping Review. Cancers, 15.","DOI":"10.3390\/cancers15184550"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Jacobs, R., and Jacobson, C.A. (2024). The Treatment of Follicular Lymphoma with CD19-Directed Chimeric Antigen Receptor T-Cell Therapy. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1384600"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41571-023-00754-1","article-title":"Long-Term Outcomes Following CAR T Cell Therapy: What We Know so Far","volume":"20","author":"Cappell","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/21\/1671\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T02:57:20Z","timestamp":1761533840000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/21\/1671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,25]]},"references-count":40,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["cells14211671"],"URL":"https:\/\/doi.org\/10.3390\/cells14211671","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,25]]}}}