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Refractory Transformed Non-Hodgkin Lymphoma

MedGen UID:
1646098
•Concept ID:
C4682697
•
Neoplastic Process
Synonym: Refractory Transformed Lymphoma

Definition

An indolent non-Hodgkin lymphoma which has undergone histologic transformation to an aggressive non-Hodgkin lymphoma and has become resistant to treatment. [from NCI]

Professional guidelines

PubMed

Role of CD19 Chimeric Antigen Receptor T Cells in Second-Line Large B Cell Lymphoma: Lessons from Phase 3 Trials. An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy.
Perales MA, Anderson LD Jr, Jain T, Kenderian SS, Oluwole OO, Shah GL, Svoboda J, Hamadani M
Transplant Cell Ther 2022 Sep;28(9):546-559. Epub 2022 Jun 26 doi: 10.1016/j.jtct.2022.06.019. PMID: 35768052Free PMC Article
Treatment patterns and outcomes of patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy (LEO CReWE): a multicentre cohort study.
Casulo C, Larson MC, Lunde JJ, Habermann TM, Lossos IS, Wang Y, Nastoupil LJ, Strouse C, Chihara D, Martin P, Cohen JB, Kahl BS, Burack WR, Koff JL, Mun Y, Masaquel A, Wu M, Wei MC, Shewade A, Li J, Cerhan J, Flowers CR, Link BK, Maurer MJ
Lancet Haematol 2022 Apr;9(4):e289-e300. doi: 10.1016/S2352-3026(22)00033-3. PMID: 35358443Free PMC Article
NCCN Guidelines Insights: B-Cell Lymphomas, Version 3.2019.
Zelenetz AD, Gordon LI, Abramson JS, Advani RH, Bartlett NL, Caimi PF, Chang JE, Chavez JC, Christian B, Fayad LE, Glenn MJ, Habermann TM, Lee Harris N, Hernandez-Ilizaliturri F, Kaminski MS, Kelsey CR, Khan N, Krivacic S, LaCasce AS, Mehta A, Nademanee A, Rabinovitch R, Reddy N, Reid E, Roberts KB, Smith SD, Snyder ED, Swinnen LJ, Vose JM, Dwyer MA, Sundar H
J Natl Compr Canc Netw 2019 Jun 1;17(6):650-661. doi: 10.6004/jnccn.2019.0029. PMID: 31200358

Recent clinical studies

Etiology

Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial.
Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Maloney DG, Crotta A, Montheard S, Previtali A, Stepan L, Ogasawara K, Mack T, Abramson JS; TRANSFORM Investigators
Lancet 2022 Jun 18;399(10343):2294-2308. doi: 10.1016/S0140-6736(22)00662-6. PMID: 35717989
Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial.
Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, Kahl BS, Radford J, Solh M, Stathis A, Zinzani PL, Havenith K, Feingold J, He S, Qin Y, Ungar D, Zhang X, Carlo-Stella C
Lancet Oncol 2021 Jun;22(6):790-800. Epub 2021 May 11 doi: 10.1016/S1470-2045(21)00139-X. PMID: 33989558
Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study.
Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Albertson TM, Garcia J, Kostic A, Mallaney M, Ogasawara K, Newhall K, Kim Y, Li D, Siddiqi T
Lancet 2020 Sep 19;396(10254):839-852. Epub 2020 Sep 1 doi: 10.1016/S0140-6736(20)31366-0. PMID: 32888407
Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial.
Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS
Lancet Oncol 2019 Jan;20(1):31-42. Epub 2018 Dec 2 doi: 10.1016/S1470-2045(18)30864-7. PMID: 30518502Free PMC Article
Transformed follicular lymphoma.
Fischer T, Zing NPC, Chiattone CS, Federico M, Luminari S
Ann Hematol 2018 Jan;97(1):17-29. Epub 2017 Oct 18 doi: 10.1007/s00277-017-3151-2. PMID: 29043381

Diagnosis

Treatment patterns and outcomes of patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy (LEO CReWE): a multicentre cohort study.
Casulo C, Larson MC, Lunde JJ, Habermann TM, Lossos IS, Wang Y, Nastoupil LJ, Strouse C, Chihara D, Martin P, Cohen JB, Kahl BS, Burack WR, Koff JL, Mun Y, Masaquel A, Wu M, Wei MC, Shewade A, Li J, Cerhan J, Flowers CR, Link BK, Maurer MJ
Lancet Haematol 2022 Apr;9(4):e289-e300. doi: 10.1016/S2352-3026(22)00033-3. PMID: 35358443Free PMC Article
High-risk follicular lymphoma: Treatment options.
Kahl B
Hematol Oncol 2021 Jun;39 Suppl 1:94-99. doi: 10.1002/hon.2853. PMID: 34105813
Ibrutinib plus lenalidomide and rituximab has promising activity in relapsed/refractory non-germinal center B-cell-like DLBCL.
Goy A, Ramchandren R, Ghosh N, Munoz J, Morgan DS, Dang NH, Knapp M, Delioukina M, Kingsley E, Ping J, Beaupre DM, Neuenburg JK, Ruan J
Blood 2019 Sep 26;134(13):1024-1036. Epub 2019 Jul 22 doi: 10.1182/blood.2018891598. PMID: 31331917Free PMC Article
Novel agents for relapsed and refractory follicular lymphoma.
Cheah CY, Fowler NH
Best Pract Res Clin Haematol 2018 Mar;31(1):41-48. Epub 2017 Nov 16 doi: 10.1016/j.beha.2017.11.003. PMID: 29452665
Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial.
Wang M, Fowler N, Wagner-Bartak N, Feng L, Romaguera J, Neelapu SS, Hagemeister F, Fanale M, Oki Y, Pro B, Shah J, Thomas S, Younes A, Hosing C, Zhang L, Newberry KJ, Desai M, Cheng N, Badillo M, Bejarano M, Chen Y, Young KH, Champlin R, Kwak L, Fayad L
Leukemia 2013 Sep;27(9):1902-9. Epub 2013 Apr 2 doi: 10.1038/leu.2013.95. PMID: 23545991

Therapy

Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial.
Hutchings M, Morschhauser F, Iacoboni G, Carlo-Stella C, Offner FC, Sureda A, Salles G, Martínez-Lopez J, Crump M, Thomas DN, Morcos PN, Ferlini C, Bröske AE, Belousov A, Bacac M, Dimier N, Carlile DJ, Lundberg L, Perez-Callejo D, Umaña P, Moore T, Weisser M, Dickinson MJ
J Clin Oncol 2021 Jun 20;39(18):1959-1970. Epub 2021 Mar 19 doi: 10.1200/JCO.20.03175. PMID: 33739857Free PMC Article
Recent advances in CAR-T cell engineering.
Huang R, Li X, He Y, Zhu W, Gao L, Liu Y, Gao L, Wen Q, Zhong JF, Zhang C, Zhang X
J Hematol Oncol 2020 Jul 2;13(1):86. doi: 10.1186/s13045-020-00910-5. PMID: 32616000Free PMC Article
Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors.
Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M, Nandivada V, Kaur I, Nunez Cortes A, Cao K, Daher M, Hosing C, Cohen EN, Kebriaei P, Mehta R, Neelapu S, Nieto Y, Wang M, Wierda W, Keating M, Champlin R, Shpall EJ, Rezvani K
N Engl J Med 2020 Feb 6;382(6):545-553. doi: 10.1056/NEJMoa1910607. PMID: 32023374Free PMC Article
Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial.
Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS
Lancet Oncol 2019 Jan;20(1):31-42. Epub 2018 Dec 2 doi: 10.1016/S1470-2045(18)30864-7. PMID: 30518502Free PMC Article
Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY
N Engl J Med 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10 doi: 10.1056/NEJMoa1707447. PMID: 29226797Free PMC Article

Prognosis

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial.
Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, Kahl BS, Radford J, Solh M, Stathis A, Zinzani PL, Havenith K, Feingold J, He S, Qin Y, Ungar D, Zhang X, Carlo-Stella C
Lancet Oncol 2021 Jun;22(6):790-800. Epub 2021 May 11 doi: 10.1016/S1470-2045(21)00139-X. PMID: 33989558
Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial.
Hutchings M, Morschhauser F, Iacoboni G, Carlo-Stella C, Offner FC, Sureda A, Salles G, Martínez-Lopez J, Crump M, Thomas DN, Morcos PN, Ferlini C, Bröske AE, Belousov A, Bacac M, Dimier N, Carlile DJ, Lundberg L, Perez-Callejo D, Umaña P, Moore T, Weisser M, Dickinson MJ
J Clin Oncol 2021 Jun 20;39(18):1959-1970. Epub 2021 Mar 19 doi: 10.1200/JCO.20.03175. PMID: 33739857Free PMC Article
Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial.
Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS
Lancet Oncol 2019 Jan;20(1):31-42. Epub 2018 Dec 2 doi: 10.1016/S1470-2045(18)30864-7. PMID: 30518502Free PMC Article
Transformed follicular lymphoma.
Fischer T, Zing NPC, Chiattone CS, Federico M, Luminari S
Ann Hematol 2018 Jan;97(1):17-29. Epub 2017 Oct 18 doi: 10.1007/s00277-017-3151-2. PMID: 29043381
Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY
N Engl J Med 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10 doi: 10.1056/NEJMoa1707447. PMID: 29226797Free PMC Article

Clinical prediction guides

Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial.
Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Maloney DG, Crotta A, Montheard S, Previtali A, Stepan L, Ogasawara K, Mack T, Abramson JS; TRANSFORM Investigators
Lancet 2022 Jun 18;399(10343):2294-2308. doi: 10.1016/S0140-6736(22)00662-6. PMID: 35717989
Treatment patterns and outcomes of patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy (LEO CReWE): a multicentre cohort study.
Casulo C, Larson MC, Lunde JJ, Habermann TM, Lossos IS, Wang Y, Nastoupil LJ, Strouse C, Chihara D, Martin P, Cohen JB, Kahl BS, Burack WR, Koff JL, Mun Y, Masaquel A, Wu M, Wei MC, Shewade A, Li J, Cerhan J, Flowers CR, Link BK, Maurer MJ
Lancet Haematol 2022 Apr;9(4):e289-e300. doi: 10.1016/S2352-3026(22)00033-3. PMID: 35358443Free PMC Article
Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial.
Hutchings M, Morschhauser F, Iacoboni G, Carlo-Stella C, Offner FC, Sureda A, Salles G, Martínez-Lopez J, Crump M, Thomas DN, Morcos PN, Ferlini C, Bröske AE, Belousov A, Bacac M, Dimier N, Carlile DJ, Lundberg L, Perez-Callejo D, Umaña P, Moore T, Weisser M, Dickinson MJ
J Clin Oncol 2021 Jun 20;39(18):1959-1970. Epub 2021 Mar 19 doi: 10.1200/JCO.20.03175. PMID: 33739857Free PMC Article
Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study.
Italiano A, Soria JC, Toulmonde M, Michot JM, Lucchesi C, Varga A, Coindre JM, Blakemore SJ, Clawson A, Suttle B, McDonald AA, Woodruff M, Ribich S, Hedrick E, Keilhack H, Thomson B, Owa T, Copeland RA, Ho PTC, Ribrag V
Lancet Oncol 2018 May;19(5):649-659. Epub 2018 Apr 9 doi: 10.1016/S1470-2045(18)30145-1. PMID: 29650362
PD-1 expression and clinical PD-1 blockade in B-cell lymphomas.
Xu-Monette ZY, Zhou J, Young KH
Blood 2018 Jan 4;131(1):68-83. Epub 2017 Nov 8 doi: 10.1182/blood-2017-07-740993. PMID: 29118007Free PMC Article

Recent systematic reviews

A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells.
Fergusson NJ, Adeel K, Kekre N, Atkins H, Hay KA
Front Immunol 2023;14:1178403. Epub 2023 Apr 27 doi: 10.3389/fimmu.2023.1178403. PMID: 37180149Free PMC Article
Clinical outcomes in patients relapsed/refractory after ≥2 prior lines of therapy for follicular lymphoma: a systematic literature review and meta-analysis.
Kanters S, Ball G, Kahl B, Wiesinger A, Limbrick-Oldfield EH, Sudhindra A, Snider JT, Patel AR
BMC Cancer 2023 Jan 23;23(1):74. doi: 10.1186/s12885-023-10546-6. PMID: 36690960Free PMC Article
A Matching-Adjusted Indirect Comparison of Single-Arm Trials in Patients with Relapsed or Refractory Follicular Lymphoma Who Received at Least Two Prior Systemic Treatments: Tazemetostat was Associated with a Lower Risk for Safety Outcomes Versus the PI3-Kinase Inhibitors Idelalisib, Duvelisib, Copanlisib, and Umbralisib.
Proudman D, Nellesen D, Gupta D, Adib D, Yang J, Mamlouk K
Adv Ther 2022 Apr;39(4):1678-1696. Epub 2022 Feb 14 doi: 10.1007/s12325-022-02054-z. PMID: 35157216Free PMC Article
Chimeric antigen receptor T-cell therapy in adults with B-cell acute lymphoblastic leukemia.
Grover P, Veilleux O, Tian L, Sun R, Previtera M, Curran E, Muffly L
Blood Adv 2022 Mar 8;6(5):1608-1618. doi: 10.1182/bloodadvances.2020003482. PMID: 34610109Free PMC Article
Yttrium 90 ibritumomab tiuxetan in lymphoma.
Cheung MC, Haynes AE, Stevens A, Meyer RM, Imrie K; Members of the Hematology Disease Site Group of the Cancer Care Ontario Program in Evidence-Based Care
Leuk Lymphoma 2006 Jun;47(6):967-77. doi: 10.1080/10428190600572582. PMID: 16840185

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