High-grade B-cell lymphoma

Section editor
	Tarsheen Sethi, MD, MSCI Yale University New Haven, CT, USA LinkedIn

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.

6 regimens on this page 6 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any article published 5+ years ago to be for historical purposes, only.

NCCN

• NCCN does not 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

1. 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

1. 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
   1. 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
   2. 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
   3. 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)

References

1. 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
   1. 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 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

1. 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 cycles for up to 18 cycles (1 year)

References

1. 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 range given is the FDA-recommended dose used in JULIET.

Preceding treatment

• Lymphodepleting therapy with FC or Bendamustine

Immunotherapy

• Tisagenlecleucel (Kymriah) 0.6 to 6 x 10⁸ CTL019 transduced viable T-cells IV once on day 0

One course

References

1. 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 PubMed NCT02445248
   1. 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