Diffuse Large B Cell Lymphoma (DLBCL) (Non-Hodgkin Lymphoma)

Regimen Options

Last Updated: 11/03/2025 See Details

NOTE: FOR RITUXIMAB, THE USE OF A BIOSIMILAR OR THE REFERENCE PRODUCT IS ON PATHWAY

	Evolent Pathways	Febrile Neutropenic Risk	Emetogenic Risk	References
DLBC LYMPHOMA
Primary/Initial Therapy	R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)	Intermediate	High	NCCN Guidelines® for B-Cell Lymphomas V.4.2017. Coiffier B, et al. N Engl J Med. 2002;346(4):235-42. Pfreundschuh M, et al. Lancet Oncol. 2008;9(2):105-16. Brusamolino E, et al. Haematologica. 2006;91(4):496-502.
Relapsed/Refractory	R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)	Intermediate	High	NCCN Guidelines® for B-Cell Lymphomas V.4.2017. Friedberg JW, et al. ASH Education Book. 2011.Vol.1.498-505. Lalit SR, et al. South Asian J Cancer. 2014;3(1):66-70. Coiffier B, et al. N Engl J Med. 2002;346(4):235-42. Pfreundschuh M, et al. Lancet Oncol. 2008;9(2):105-16. Brusamolino E, et al. Haematologica. 2006;91(4):496-502.
	R-CEOP (rituximab, cyclophosphamide, etoposide, vincristine and prednisone)	Low	Moderate	NCCN Guidelines® for B-Cell Lymphomas V.4.2017. Moccia AA, et al. Blood. 2009;114(22):abstr408.
	R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin hydrochloride)	Intermediate	High	NCCN Guidelines® for B-Cell Lymphomas V.4.2017. Wilson WH, et al. J Clin Oncol. 2008;26(16):52717-24. Wilson WH, et al. Blood. 2002;99(8):2685-93. Malecek MK, et al. Am J Hematol. 2017. Alinari L, et al. Am J Hematol. 2016;91(4):395-9.
	Dose adjusted R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin)	Intermediate	Moderate	NCCN Guidelines® for B-Cell Lymphomas V.4.2017. Purroy N, et al. Br J Haematol. 2015;169(2). Wilson WH, et al. J Clin Oncol. 2008.26(16):2717-24a. Wilson WH, et al. Blood. 2002:99(8):2685-93.
	R-ICE (rituximab, ifosfamide, carboplatin and etoposide)	High	High	NCCN Guidelines® for B-Cell Lymphomas V.4.2017. Kewalramani T, et al. Blood. 2004;103(10):3684-88.
	R-DHAP (rituximab, dexamethasone, cytarabine and cisplatin)	High	High	NCCN Guidelines® for B-Cell Lymphomas V.4.2017. Velasquez WS, et al. Blood. 1988;71(1):117-22. Mey UJ, et al. Cancer Invest. 2006;24(6):593-600.
	R-ESHAP (rituximab, etoposide, methylprednisolone, high-dose cytarabine, cisplatin)	High	High	NCCN Guidelines® for B-Cell Lymphomas V.4.2017. Velasquez WS, et al. J Clin Oncol. 1994;12(6):1169-76. Martin A, et al. Haematologica. 2008;93(12):1829-36.
	GemOx (gemcitabine, oxaliplatin)	Low	Moderate	NCCN Guidelines® for B-Cell Lymphomas V.4.2017. Lopez A, et al. Eur J Haematol. 2008;80(2):127-32. Rodriguez J, et al. Leuk Lymphoma. 2007;48(11):2172-8.
	R-GemOx (rituximab, gemcitabine and oxaliplatin)	Low	Moderate	NCCN Guidelines® for B-Cell Lymphomas V.4.2017. Lopez A, et al. Eur J Haematol. 2008;80(2):127-32. Rodriguez J, et al. Leuk Lymphoma. 2007;48(11):2172-8.
	GDP (gemcitabine, dexamethasone, cisplatin)	Intermediate	High	NCCN Guidelines® for B-Cell Lymphomas V.4.2017. Gopal Ak, et al. Leuk Lymphoma. 2010;51(8):1523-9.
	R-GDP (rituximab, gemcitabine, dexamethasone and cisplatin)	Intermediate	High	NCCN Guidelines® for B-Cell Lymphomas V.4.2017. Gopal Ak, et al. Leuk Lymphoma. 2010;51(8):1523-9.
CAR T-cell Candidates: 2nd Line	axicabtagene ciloleucel (Yescarta)	Low	Low	NCCN Guidelines® for B-Cell Lymphomas V.3.2025. Locke, FL et al. N Engl J Med 2022;386:640-654
	lisocabtagene maraleucel (Breyanzi)	Low	Low	NCCN Guidelines® for B-Cell Lymphomas V.3.2025. Abramson, JS et al. Blood (2023) 141 (14): 1675–1684.
Not CAR T-cell Candidates: 2nd Line	epcoritamab-bysp (Epkinly), gemcitabine and oxaliplatin	Low	Moderate	NCCN Guidelines® for B-Cell Lymphomas V.3.2025. Brody, JD et al. Blood (2025) 145 (15): 1621–1631.
	glofitamab-gxbm (Columvi), gemcitabine and oxaliplatin	Low	Moderate	NCCN Guidelines® for B-Cell Lymphomas V.3.2025. Abramson, JS et al. DOI: 10.1016/S0140-6736(24)01774-4
3rd & Subsequent Therapy	axicabtagene ciloleucel (Yescarta)	Low	Low	NCCN Guidelines® for B-Cell Lymphomas V.3.2025. Locke, FL et al. N Engl J Med 2022;386:640-654
	lisocabtagene maraleucel (Breyanzi)	Low	Low	NCCN Guidelines® for B-Cell Lymphomas V.3.2025. Abramson, JS et al. Blood (2023) 141 (14): 1675–1684.
	tisagenlecleucel (Kymriah)	Intermediate	Low	NCCN Guidelines® for B-Cell Lymphomas V.3.2025. Schuster, SJ et al. N Engl J Med. 2019 Jan 3;380(1):45-56.
	epcoritamab-bysp (Epkinly)	Low	Low	NCCN Guidelines® for B-Cell Lymphomas V.3.2025. Linton, KM et al. DOI: 10.1016/S2352-3026(24)00166-2
	glofitamab-gxbm (Columvi)	Low	Minimal	NCCN Guidelines® for B-Cell Lymphomas V.3.2025. Dickinson MJ, et al. N Engl J Med 2022;387:2220-2231
	Best Supportive Care or Clinical Trial	Not Applicable	Not applicable	1. NCCN Guidelines® for Supportive Care.
DOUBLE/TRIPLE HIT LYMPHOMA
	Dose adjusted R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin)	Intermediate	Moderate	NCCN Guidelines® for B-Cell Lymphomas V.4.2017. Purroy N et al. Br J Haematol . 2015 Apr;169(2):188-98.
	R-HyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin and dexamethasone)	High	Moderate	NCCN Guidelines® for B-Cell Lymphomas V.4.2017. Tsai J et al. https://doi.org/10.1182/blood.V122.21.4361.4361

DLBC LYMPHOMA

Primary/Initial Therapy

Evolent Pathways

R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)

Febrile Neutropenic Risk

intermediate

Emetogenic Risk

high

References

Relapsed/Refractory

Evolent Pathways

R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)

Febrile Neutropenic Risk

intermediate

Emetogenic Risk

high

References

Evolent Pathways

R-CEOP (rituximab, cyclophosphamide, etoposide, vincristine and prednisone)

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

Evolent Pathways

R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin hydrochloride)

Febrile Neutropenic Risk

intermediate

Emetogenic Risk

high

References

Evolent Pathways

Dose adjusted R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin)

Febrile Neutropenic Risk

intermediate

Emetogenic Risk

moderate

References

Evolent Pathways

R-ICE (rituximab, ifosfamide, carboplatin and etoposide)

Febrile Neutropenic Risk

high

Emetogenic Risk

high

References

Evolent Pathways

R-DHAP (rituximab, dexamethasone, cytarabine and cisplatin)

Febrile Neutropenic Risk

high

Emetogenic Risk

high

References

Evolent Pathways

R-ESHAP (rituximab, etoposide, methylprednisolone, high-dose cytarabine, cisplatin)

Febrile Neutropenic Risk

high

Emetogenic Risk

high

References

Evolent Pathways

GemOx (gemcitabine, oxaliplatin)

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

Evolent Pathways

R-GemOx (rituximab, gemcitabine and oxaliplatin)

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

Evolent Pathways

GDP (gemcitabine, dexamethasone, cisplatin)

Febrile Neutropenic Risk

intermediate

Emetogenic Risk

high

References

Evolent Pathways

R-GDP (rituximab, gemcitabine, dexamethasone and cisplatin)

Febrile Neutropenic Risk

intermediate

Emetogenic Risk

high

References

CAR T-cell Candidates: 2nd Line

Evolent Pathways

axicabtagene ciloleucel (Yescarta)

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

lisocabtagene maraleucel (Breyanzi)

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Not CAR T-cell Candidates: 2nd Line

Evolent Pathways

epcoritamab-bysp (Epkinly), gemcitabine and oxaliplatin

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

Evolent Pathways

glofitamab-gxbm (Columvi), gemcitabine and oxaliplatin

Febrile Neutropenic Risk

low

Emetogenic Risk

moderate

References

3rd & Subsequent Therapy

Evolent Pathways

axicabtagene ciloleucel (Yescarta)

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

lisocabtagene maraleucel (Breyanzi)

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

tisagenlecleucel (Kymriah)

Febrile Neutropenic Risk

intermediate

Emetogenic Risk

low

References

Evolent Pathways

epcoritamab-bysp (Epkinly)

Febrile Neutropenic Risk

low

Emetogenic Risk

low

References

Evolent Pathways

glofitamab-gxbm (Columvi)

Febrile Neutropenic Risk

low

Emetogenic Risk

minimal

References

Evolent Pathways

Best Supportive Care or Clinical Trial

Febrile Neutropenic Risk

Emetogenic Risk

References

DOUBLE/TRIPLE HIT LYMPHOMA

Evolent Pathways

Dose adjusted R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin)

Febrile Neutropenic Risk

intermediate

Emetogenic Risk

moderate

References

Evolent Pathways

R-HyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin and dexamethasone)

Febrile Neutropenic Risk

high

Emetogenic Risk

moderate

References

	Regimen	Alternative
LOW VALUE REGIMENS (NON-PATHWAY) WITH SUPERIOR ALTERNATIVES
	lenalidomide maintenance	Alternative: no maintenance therapy
	rituximab maintenance (continuation of single-agent rituximab after completion of initial chemotherapy)	Alternative: no maintenance therapy

LOW VALUE REGIMENS (NON-PATHWAY) WITH SUPERIOR ALTERNATIVES

Regimen

** lenalidomide maintenance **

Regimen

** rituximab maintenance (continuation of single-agent rituximab after completion of initial chemotherapy) **

Pathways and Low-Value Regimens

Diffuse Large B Cell Lymphoma (DLBCL) (Non-Hodgkin Lymphoma)