Table 2.

Summary of Treatment Recommendations for DLBCL

NCCN Guidelines7			ESMO Guidelines33,34
Classification		Treatment Options	Classification		Treatment Options
Ann Arbor stage I or II	Nonbulky	• R-CHOPa x 3 cycles + IFRT or • R-CHOPa x 6 cycles ± IFRT • IFRT for noncandidates for chemotherapy	Young	IPI low risk with no bulk	• R-CHOP21 x 6 cycles
	Bulky	• R-CHOPa x 6 cycles ± locoregional Rt		IPI low risk with bulk or low-intermediate risk	• R-ACVBP with sequential consolidation or • R-CHOP21 x 6 cycles + IFRT on bulk
Ann Arbor stage III or IV		• Clinical trials or • R-CHOP21 • Alternatives: DA-EPOCH + R or dose-dense R-CHOP14		IPI intermediate-high risk or high risk	• R-CHOP21 x 8 cycles or R-CHOP14 x 6 with 8 cycles R • More intensive regimens: R-CHOEP14 x 6 cycles or R-ACVBP + HDCT with ASCT or R-dose-dense (R-CHOP14—like) + R-HDCT with ASCT
For >80 year with comorbidities		• R-miniCHOP	Elderly	>60 year, healthy	• R-CHOP21 x 8 cycles • (R-CHOP21 x 6 cycles for IPI low risk) or • R-CHOP14 x 6 with 8 cycles R
For very frail or with poor LVF		• R-CEPP • R-CDOP • R-CNOP • DA-EPOCH + R • R-CEOP		>80 year without cardiac dysfunction	• Attenuated regimen: R-miniCHOP21 x 6 cycles
				Unfit/frail or >60 year with cardiac dysfunction	• R-C(X)OP21 x 6 cycles or • Palliative care
Relapse/refractory	Intend to proceed to high-dose therapy	Second-line and subsequent: • DHAP ± R • ESHAP ± R • GDP ± R • GemOx ± R • ICE ± R • MINE ± R	First relapse/progress	Eligible to transplant	•Salvage regimen with platinum-based chemotherapy regimens (ie, R-DHAP, R-IcE) • R-HDCT with ASCT for chemosensitive patients • Allogeneic transplantation for relapsed after R-HDCT with ASCT or with poor risk at relapse
	Noncandidates for high-dose therapy	Clinical trial or second and subsequent lines: • Bendamustine ± R • Brentuximab vedotin (for CD30+ disease) • CEPP ± R • CEOP ± R • DA-EPOCH ± R • GDP ± R • GemOx ± R • Lenalidomide ± R • R or • Palliative RT or • Best supportive care		Not eligible to transplant	•Platinum and/or gemcitabine-based regimens or • Clinical trials with novel drugs
			>2 relapse/progress	Eligible to transplant	• Allogeneic transplantation or • Clinical trials with novel drugs
				Not eligible to transplant	• Clinical trials with novel drugs or • Palliative care

Abbreviations: ACVBP = doxorubicin, vindesine, cyclophosphamide, bleomycin, and prednisolone; ASCT = autologous stem cell transplantation; CDOP = cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone; CEOP = cyclophosphamide, etoposide, vincristine, and prednisone; CEPP = cyclophosphamide, etoposide, prednisone, and procarbazine; CHOEP = cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone; CHOP=cyclophosphamide, doxorubicin, vincristine, and prednisone; CHOP14=cyclophosphamide, doxorubicin, vincristine, and prednisone dosed for 14 days; CHOP21 = cyclophosphamide, doxorubicin, vincristine, and prednisone dosed for 21 days; CNOP = cyclophosphamide, mitoxantrone, vincristine, and prednisone; DA-EPOCH = dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin; DHAP=dexamethasone, cisplatin, cytarabine; DLBCL=diffuse large B-cell lymphoma, ESHAP=etoposide, methylprednisolone, cytarabine, and cisplatin; ESMO = European Society for Medical Oncology; GDP = gemcitabine, dexamethasone, and cisplatin/carboplatin; GemOX = gemcitabine and oxaliplatin; HDCT = high-dose chemotherapy; ICE = ifosfamide, carboplatin, and etoposide; IFRT = involved-field radiation therapy; IPI = International Prognostic Index; LVF = left-ventricular function; MINE = mesna, ifosfamide, mitoxantrone, and etoposide; NCCN= National Comprehensive Cancer Network; R= rituximab; R-miniCHOP = rituximab plus reduced dose cyclophosphamide, doxorubicin, vincristine, and prednisone; RT = radiation therapy; X = doxorubicin substitution with etoposide, liposomal doxorubicin, others.

^aFor patients who are intolerant to anthracyclines, alternative chemoimmunotherapies include R-CEPP, R-CDOP, R-CNOP, DA-EPOCH plus rituximab, and R-CEOP, which are also recommended first-line therapy for patients with poor left ventricular function or very frail patients.