High-grade B-cell lymphoma
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Tarsheen Sethi, MD, MSCI Yale University New Haven, CT, USA |
Note: High-grade B-cell lymphoma (HGBL) was not considered as a named entity until the 2016 revision of the WHO guidelines, and includes entities such as double-hit lymphoma and triple-hit lymphoma which were previously classified under diffuse large B-cell lymphoma. We will populate this page with relevant regimens over time.
7 regimens on this page
7 variants on this page
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Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - B-cell Lymphomas.
Untreated
Pola-R-CHP
Pola-R-CHP: Polatuzumab, Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Prednisone
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Tilly et al. 2021 (POLARIX) | 2017-2019 | Phase 3 (E-RT-switch-ooc) | R-CHOP | Superior PFS (primary endpoint) PFS24: 76.7% vs 70.2% (HR 0.73, 95% CI 0.57-0.95) |
Note: 26 patients in the experimental arm had double- or triple-hit lymphoma.
Antibody-drug conjugate therapy
- Polatuzumab vedotin (Polivy) as follows:
- Cycles 1 to 6: 1.8 mg/kg IV once on day 1
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 6: 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) as follows:
- Cycles 1 to 6: 50 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) as follows:
- Cycles 1 to 6: 100 mg PO once per day on days 1 to 5
21-day cycle for 8 cycles
References
- POLARIX: Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trněný M, Sharman JP, Herbaux C, Burke JM, Matasar M, Rai S, Izutsu K, Mehta-Shah N, Oberic L, Chauchet A, Jurczak W, Song Y, Greil R, Mykhalska L, Bergua-Burgués JM, Cheung MC, Pinto A, Shin HJ, Hapgood G, Munhoz E, Abrisqueta P, Gau JP, Hirata J, Jiang Y, Yan M, Lee C, Flowers CR, Salles G. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022 Jan 27;386(4):351-363. Epub 2021 Dec 14. link to original article contains dosing details in manuscript PubMed NCT03274492
R-CHOP
R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Tilly et al. 2021 (POLARIX) | 2017-2019 | Phase 3 (C) | Pola-R-CHP | Inferior PFS |
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 6: 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) as follows:
- Cycles 1 to 6: 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) as follows:
- Cycles 1 to 6: 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) as follows:
- Cycles 1 to 6: 100 mg PO once per day on days 1 to 5
21-day cycle for 8 cycles
References
- POLARIX: Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trněný M, Sharman JP, Herbaux C, Burke JM, Matasar M, Rai S, Izutsu K, Mehta-Shah N, Oberic L, Chauchet A, Jurczak W, Song Y, Greil R, Mykhalska L, Bergua-Burgués JM, Cheung MC, Pinto A, Shin HJ, Hapgood G, Munhoz E, Abrisqueta P, Gau JP, Hirata J, Jiang Y, Yan M, Lee C, Flowers CR, Salles G. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022 Jan 27;386(4):351-363. Epub 2021 Dec 14. link to original article contains dosing details in manuscript PubMed NCT03274492
Relapsed or refractory, subsequent lines of therapy
Axicabtagene ciloleucel monotherapy
Regimen
| FDA-recommended dose |
| Study | Dates of enrollment | Evidence | Efficacy |
|---|---|---|---|
| Locke et al. 2017 (ZUMA-1) | 2015-2016 | Phase 1/2 (RT), fewer than 20 patients in this subgroup | ORR: 83%; CR: 59%
Median OS: not reached Median PFS: 6 months Median duration of response: 11 months |
Preceding treatment
- Lymphodepletion with FC
Immunotherapy
- Axicabtagene ciloleucel (Yescarta) target dose of 2 × 106 CAR T cells/kg IV once on day 0
Supportive therapy
- Acetaminophen (Tylenol) 650 mg PO once on day 0, approximately 60 minutes prior to axi-cel
- Diphenhydramine (Benadryl) 12.5 mg IV or PO once on day 0, approximately 60 minutes prior to axi-cel
One course; patients with initial response and disease progression at least 3 months later could be retreated
References
- ZUMA-1: Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02348216
- Update: 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. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10. link to original article contains dosing details in manuscript link to PMC article PubMed
- Update: 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. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. Epub 2018 Dec 2. link to original article link to PMC article contains dosing details in manuscript PubMed
- Update: Neelapu SS, Jacobson CA, Ghobadi A, 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 AH, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Bot AA, Shen RR, Dong J, Singh K, Miao H, Kim JJ, Zheng Y, Locke FL. Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2023 May 11;141(19):2307-2315. link to original article PubMed
Epcoritamab monotherapy
Regimen
| Study | Dates of enrollment | Evidence |
|---|---|---|
| Hutchings et al. 2021 (EPCORE NHL-1) | 2020-06-19 to 2022-01-31 | Phase 1/2 (RT), fewer than 20 patients in this subgroup |
Note: dates of enrollment are based on the dose-expansion cohort.
Immunotherapy
- Epcoritamab (Epkinly) as follows:
- Cycle 1: 0.16 mg SC once on day 1, then 0.8 mg SC once on day 8, then 48 mg SC once per day on days 15 & 22
- Cycles 2 & 3: 48 mg SC once per day on days 1, 8, 15, 22
- Cycles 4 to 9: 48 mg SC once per day on days 1 & 15
- Cycle 10 onwards: 48 mg SC once on day 1
Supportive therapy
- Prednisolone (Millipred) as follows:
- Cycle 1: 100 mg PO or IV once per day on days 1 to 4, 8 to 11, 15 to 18, 22 to 25, given 30 to 120 minutes prior to epcoritamab on treatment days 1, 8, 15, 22
- Diphenhydramine (Benadryl) as follows:
- Cycle 1: 50 mg PO or IV once per day on days 1, 8, 15, 22
- Acetaminophen (Tylenol) as follows:
- Cycle 1: 650 to 1000 mg PO once per day on days 1, 8, 15, 22
28-day cycles
References
- EPCORE NHL-1: Hutchings M, Mous R, Clausen MR, Johnson P, Linton KM, Chamuleau MED, Lewis DJ, Sureda Balari A, Cunningham D, Oliveri RS, Elliott B, DeMarco D, Azaryan A, Chiu C, Li T, Chen KM, Ahmadi T, Lugtenburg PJ. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet. 2021 Sep 25;398(10306):1157-1169. Epub 2021 Sep 8. link to original article PubMed NCT03625037
- Update: Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, Do YR, Feldman T, Gasiorowski R, Jurczak W, Kim TM, Lewis DJ, van der Poel M, Poon ML, Cota Stirner M, Kilavuz N, Chiu C, Chen M, Sacchi M, Elliott B, Ahmadi T, Hutchings M, Lugtenburg PJ. Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. J Clin Oncol. 2023 Apr 20;41(12):2238-2247. Epub 2022 Dec 22. link to original article link to PMC article contains dosing details in manuscript PubMed
Lisocabtagene maraleucel monotherapy
Regimen
| Study | Dates of enrollment | Evidence |
|---|---|---|
| Abramson et al. 2020 (TRANSCEND NHL-001) | 2016-01-11 to 2019-07-05 | Phase 1 (RT) |
Immunotherapy
- Lisocabtagene maraleucel (Breyanzi) target dose of 100 x 106 CAR T cells IV once on day 0
One course
References
- TRANSCEND NHL-001: 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. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839-852. Epub 2020 Sep 1. link to original article contains dosing details in abstract PubMed NCT02631044
Loncastuximab tesirine monotherapy
Regimen
| FDA-recommended dose |
| Study | Dates of enrollment | Evidence |
|---|---|---|
| Caimi et al. 2021 (LOTIS-2) | 2018-2019 | Phase 2 (RT) |
Antibody-drug conjugate therapy
- Loncastuximab tesirine (Zynlonta) as follows:
- Cycles 1 & 2: 0.15 mg/kg IV over 30 minutes once on day 1
- Cycles 3 to 18: 0.075 mg/kg IV over 30 minutes once on day 1
Supportive therapy
- Dexamethasone (Decadron) 4 mg IV or PO twice per day on days -1 to 2 (3 days total)
21-day cycle for up to 18 cycles (1 year)
References
- LOTIS-2: 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. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):790-800. Epub 2021 May 11. link to original article contains dosing details in abstract PubMed NCT03589469
Tisagenlecleucel monotherapy
Regimen
| FDA-recommended dose |
| Study | Dates of enrollment | Evidence | Efficacy |
|---|---|---|---|
| Schuster et al. 2018 (JULIET) | 2015-2017 | Phase 2 (RT), fewer than 20 patients in this subgroup | ORR: 59% (95% CI, 44-72) |
Note: The FDA-recommended range is 0.6 to 6 x 108 CTL019 transduced viable T-cells.
Preceding treatment
- Lymphodepletion with FC or Bendamustine
Immunotherapy
- Tisagenlecleucel (Kymriah) 1 to 5 x 108 CTL019 transduced viable T-cells IV once on day 0
One course
References
- JULIET: Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. Epub 2018 Dec 1. link to original article contains dosing details in supplement PubMed NCT02445248
- Update: Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, Waller EK, Jaglowski S, Bishop MR, Damon LE, Foley SR, Westin JR, Fleury I, Ho PJ, Mielke S, Teshima T, Janakiram M, Hsu JM, Izutsu K, Kersten MJ, Ghosh M, Wagner-Johnston N, Kato K, Corradini P, Martinez-Prieto M, Han X, Tiwari R, Salles G, Maziarz RT. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1403-1415. Epub 2021 Sep 10. link to original article PubMed