Table 1.

Current standard of care in Grade 1–2 follicular lymphoma: NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) 2017⁸

First-line therapy (in order of preference)		Second-line and subsequent therapy (in order of preference)
Suggested Treatment Regimens	Consolidation/Extended dosing (optional)	Suggested Treatment Regimens	Consolidation/Extended dosing (optional)
Elderly or infirm:
• R (375 mg/m2 weekly for 4 doses)15,62–64
• Single-agent alkylators (eg, chlorambucil or cyclophosphamide) ± R
• Radioimmunotherapy[a,b] (category 2B)
B + R17,18 (category 1)	R maintenance (375 mg/m2 every 8 weeks for 12 doses for patients with initial high tumor burden50 (category 1)*	Chemoimmunotherapy (same as first-line therapy)	R maintenance (375 mg/m2 every 12 weeks for 2 years)51,52 (category 1)
R-CHOP53,54 (category 1)	R consolidation (375 mg/m2 every 8 weeks for 4 doses)**	R50,55	O maintenance for rituximab-refractory disease (1 g every 8 weeks for a total of 12 doses)26
R-CVP56 (category 1)	Radioimmunotherapy (after induction with chemotherapy or chemoimmunotherapy)[a,b,c] 57–59	L ± R60,61	High-dose therapy with autologous stem cell rescue
R (375 mg/m2 weekly for 4 doses)*** 15,62–64		B + O26	Allogenic stem cell transplant for highly selected patients
L + R32,66 (category 2B)		Radioimmunotherapy[a,b]61 (category 1) I[d] 65 F[e] + R67 RFND [e,f]68 Second-Line regimens for DLBCL without regard to transplantability****

Notes:

^aSelection of patients requires adequate marrow cellularity >15% and <25% involvement of lymphoma in bone marrow, and platelets >100,000. In patients with prior autologous stem cell rescue, referral to a tertiary care center is highly recommended for radioimmunotherapy.

^bIf radioimmunotherapy is considered, bilateral cores are recommended and the pathologist should provide the % of overall cellular elements and the % of cellular elements involved in the bone marrow. Cytogenetics ± FISH for known MDS markers.

^cThe full impact of an induction regimen containing rituximab on RIT consolidation is unknown.

^dSpecial considerations for the use of small-molecule inhibitors (ibrutinib and idelalisib) available from NCCN.org.

^eFludarabine-containing regimens negatively impact stem cell mobilization for transplant.

^fRFND regimen may be associated with stem cell toxicity and secondary malignancies.

^*Based on the PRIMA study for patients with high tumor burden treatment with RCVP and RCHOP. No data following other regimens.

^**If initially treated with single agent rituximab.

^***Consider for low tumor burden.

^****Intention to proceed to high-dose therapy: DHAP (dexamethasone, cisplatin, cytarabine) ± rituximab; ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) ± rituximab; GDP (gemcitabine, dexamethasone, cisplatin) ± rituximab or (gemcitabine, dexamethasone, carboplatin) ± rituximab; GemOx (gemcitabine, oxaliplatin) ± rituximab; ICE (ifosfamide carboplatin, etoposide) ± rituximab; MINE (mesna, ifosfamide, mitoxantrone, etoposide) ± rituximab. Non-candidates for high-dose therapy: Bendamustine ± rituximab; Brentuximab vedotin for CD30+ disease (category 2B); CEPP (cyclophosphamide, etoposide, prednisone, procarbazine) ± rituximab – PO and IV; CEOP (cyclophosphamide, etoposide, vincristine, prednisone) ± rituximab; DA-EPOCH ± rituximab; GDP ± rituximab or (gemcitabine, dexamethasone, carboplatin) ± rituximab; GemOx ± rituximab; Gemcitabine, vinorelbine ± rituximab (category 3B); Lenalidomide ± rituximab (non-GCB DLBCL); Rituximab. For second-line and subsequent therapy: i. Inclusion of any anthracycline or anthracenedione in patients with impaired cardiac functioning should have more frequent cardiac monitoring; ii. If additional anthracycline is administered after a full course of therapy, careful cardiac monitoring is essential. Dexrazoxane may be added as a cardioprotectant; iii. Rituximab should be included as second-line therapy if there is relapse after a reasonable remission (>6 months); however, rituximab should often be omitted in patients with primary refractory disease. All recommendations are category 2A unless otherwise indicated. Category 1: high-level evidence, there is uniform NCCN consensus that the intervention is appropriate, Category 2A: lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate, Category 2B: lower-level evidence, there is NCCN consensus that the intervention is appropriate, Category 3: any level of evidence, there is major NCCN disagreement that the intervention is appropriate. Adapted with permission from National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. B-cell Lymphomas. Version 1. 2017. Fort Washington, PA: NCCN; 2017 [updated 2017]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Accessed February 9, 2017.⁸ © 2017 National Comprehensive Cancer Network, Inc.

Abbreviations: B, bendamustine, CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; CVP, cyclophosphamide, vincristine, and prednisone; DLBCL, diffuse large B-cell lymphoma; L, lenalidomide; I, idelalisib; F, fludarabine; FISH, fluorescence in situ hybridization, FND, fludarabine, mitoxantrone, and dexamethasone; MDS, myelodysplastic syndrome, NCCN, National Comprehensive Cancer Network, O, obinutuzumab; R rituximab; RIT, radioimmunotherapy; PO, oral; IV, intravenous; DA-EPOCH, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin; GCB, germinal center B-cell like.