Table 2 Frontline treatment for localized and advanced-stage indolent lymphoma
From: How we treat mature B-cell neoplasms (indolent B-cell lymphomas)
Drug | Histology | N | Follow-up (y) | Responseˆ†: PFS**, OS, ORR, CRR | Toxicities†and comments |
|---|---|---|---|---|---|
Localized | |||||
 RT (40–45 Gy) versus low-dose RT (24 Gy) [29] (BNLI) | FL, MZL | 361 | 6 | RT: 5yOS 73%, ORR 93%, CRR 79% Low-dose RT: 5yOS 74%, ORR 92%, CRR 82% PFS: NS, OS: NS | Low-dose RT: trend for reduced toxicity (Table 1) |
 RT (24 Gy) versus VLDRT (4 Gy) [125] (FORT)‡‡ | FL, MZL | 548 | 2 | RT: ORR 91%, CRR 68% VLDRT: ORR 81%, CRR 49% | RT: G3–4 3% VLDRT: G3–4 1% (Table 1) |
 IFRT ± RCVP [64] | FL | 150 | 10 | IFRT: 10yPFS 41%; 10yOS 87% (NS) IFRT + RCVP: 10yPFS 59%; 10yOS 95% (NS) | IFRT: G3–4 2%; RCVP: G3–4 51% HT: 19% overall (NS) Staging: CT and BM |
 R + IFRT [240]  Rx8 + RT(30–40 Gy) | FL | 85 | 5.5 | 5yPFS 78%; 5yOS 96% | G3–4 AEs: 5% 14/17 relapses outside RT field |
 R versus CIT ± RT versus RT versus WW [37] | FL | 206 | 5 | RT: PFS 72 m WW/R/CIT/CIT + RT: PFS NR | Not reported Staging: CT and BM ± PET |
 RT versus RT + CIT versus CIT (or R alone) versus WW [20] | FL | 365 | 4 | RT: 5yPFS 68%, 5yOS 93% RT + CIT: 5yPFS 72%, 5yOS 95% CIT (or R alone): 5yPFS 86%, 5yOS 91% WW: similar OS to other groups, lower PFS | In-field relapse: RT 1.7%, CIT 5.0%, CIT + RM 0% Distant relapse: RT 20.4%, CIT 10.0%, CIT + RM 4.1% Staging: PET and BM |
Early stage (not meeting GELF criteria) | |||||
 R + RM versus RR [76] (RESORT) | FL | 289 | 4.5 | RR: 3yPFS 50%; TTF 4y (NS); 3y TTNT 84% MR: 3yPFS 78%, TTF 4y (NS); 3y TTNT 95% 5yOS 94% both groups | RR: HT 8 patients MR: HT 6 patients; 1 death PML |
Advanced stage (meeting GELF criteria) | |||||
 BR versus R-CHOP [96] (StiL) | FL, MCL, MZL, LPL, SLL, Other | 514 | 4 | BR: PFS 70 m; OS NS R-CHOP: PFS 31 m; OS NS *MZL: PFS difference NS | BR: lower alopecia (0% vs. 100%), hematologic (30% vs. 68%), infection (37% vs. 50%), neuropathy (7% vs. 29%), stomatitis (6% vs. 19%); higher skin tox (16% vs. 9%) |
FL, MCL, MZL, LPL | 447 | 5 | BR: 5yPFS 66%, OS NS, ORR 97%, CRR 31% R-CHOP: 5yPFS 56%, OS NS, ORR 91%, CRR 25% | As above (StiL) | |
 R2 versus R-chemo (CHOP/B/CVP) [104] (RELEVANCE) | FL | 1030 | 3 | R2: 3yPFS 77%, ORR 86% (NS); CR 48% R-chemo: 3yPFS 78%, ORR 92% (NS), CRR 53% OS: NS | R2: G3–4 cutaneous (7% vs. 1%) R-chemo: G3–4 neutropenia (32 vs. 50%), febrile neutropenia (2 vs. 7%) 20% of patients not evaluable, PFS may be underestimated |
 G-chemo (CHOP/CVP/B) versus R-chemo [91] (GALLIUM) | FL | 1202 | 3 | G-chemo: 3yPFS 80% R-chemo: 3yPFS 73% OS: NS | G-chemo: G3–5 74.6%, SAE 46.1% R-chemo: G3–5 67.8%, SAE 39.9% PFS driven by younger patients treated with BG versus BR |
 R ± chlorambucil versus chlorambucil [109] | Extra-nodal MZL (MALT) | 401 | 7 | R-chlor: 5yPFS 72%, 5yEFS 68%, ORR 94.7% R: 5y PFS57%, 5yEFS 50%, ORR 78% Chlor: 5yPFS 59%, 5yEFS 51%, ORR 86% OS: NS | HT: 10 patients total (2 chlor, 6 R-chlor, 2 R alone) AEs: no unexpected differences |
 R ± R maintenance (RM) [107] | NLPHL | 39 | 10 (R), 5 (RM) | R: 5yPFS‡ 39.1%, 5yOS‡ 95.7% R + RM: 5yPFS‡ 58.9% (NS), 5yOS‡ 85.7% | HT: 9 of 23 pts with relapse (39%) |
 Ibrutinib-R versus placebo-R [111] (iNNOVATE) | WM (1st line and relapse) | 150 | 2 | Ibrutinib-R: 30mPFS 82%, 30mOS 94% (NS), ORR 92%, CR/VGPR/PR 72% | Ibrutinib-R AEs: diarrhea, arthralgia, nausea; bleeding (51% vs. 21%) Ibrutinib-R G3–4 AEs: HTN (13% vs. 4%), afib (12% vs. 1%) |