Selected clinical trials incorporating Bv and immunotherapy in early-stage HL
| Trial . | Trial design . | Disease stage . | N . | Median follow-up . | Outcomes . | PFS . | OS . |
|---|---|---|---|---|---|---|---|
| Pembrolizumab followed by AVD51 | Pembro × 3 ⟶ AVD × 4-6 (4 cycles for early stage, 6 cycles for advanced-stage or early-stage bulky) | Stage I/II unfavorable Stage III/IV | 30 | 22.5 months | CMR 55% with pembro alone, but reached 100% after AVD × 2 | Median PFS not reached, 2-year PFS 100% | Median OS not reached, 2-year OS 100% |
| Nivolumab and AVD54 | Nivo-AVD × 4 plus 30 Gy ISRT Sequential therapy: nivo × 4 doses ⟶ nivo-AVD × 2 ⟶ AVD × 2 plus 30 Gy ISRT | Early-stage unfavorable | 109 | 13 months | CMR Group 1: 83% Group 2: CR 84% | 12-month PFS: Group 1: 100% Group 2: 98% | 12-month OS 100% in both groups |
| Bv-AVD vs ABVD, followed by 30 Gy INRT53 | Bv-AVD × 4 or ABVD × 4 ⟶ 30 Gy INRT | Early-stage unfavorable | 170 | 45 months | CMR Bv-AVD 86.7% ABVD 78.9% | 2-year PFS: 97.3% with Bv-AVD vs 92.6% with ABVD | Median not reached |
| Bv-AD45 | Bv - AD × 2 ⟶ PET 1. If PET neg, then Bv - AD × 2 (total 4) 2. If PET pos, then Bv - AD × 4 (total 6) | Non-bulky early-stage favorable or unfavorable | 34 | 53 months | CMR 97% | Estimated 5-year PFS of 91% | Estimated 5-year OS of 96% |
| Bv-AVD +/- RT (4 cohorts)52 | BV-AVD × 4 ⟶ PET If PET neg, then 1. 30 Gy ISRT 2. 20 Gy ISRT 3. 30 consolidation volume radiotherapy 4. No radiotherapy | Early-stage unfavorable | 117 | 45.6 months | CMR 1. 93% 2. 100% 3. 93% 4. 97% | Overall 2-year PFS 94% 2-year PFS for 4 cohorts 1. 93.1% 2. 97% 3. 90% 4. 97% | Overall 2-year OS 99.1% |
| ABVD followed by Bv consolidation56 | ABVD × 2 ⟶PET Favorable and PET neg, then BV consolidation Favorable and PET pos or unfavorable and PET neg, then ABVD × 2 plus BV consolidation Unfavorable and PET pos, then ABVD × 4 plus BV consolidation | Nonbulky early-stage favorable and unfavorable | 41 | 47 months | CMR 95% | 3-year PFS of 92% 3-year PFS 100% for PET neg after Bv | OS was 97% 3 year OS 100% for PET neg after Bv |
| Trials with novel agents including patients older than 60 | |||||||
| Bv followed by AVD followed by Bv consolidation43 | Bv × 2 ⟶ AVD × 6 ⟶ Bv × 4 | Stage II-IV (age 60 or older) | 48 (9 stage II) | 23 months | CMR 90% after Bv-AVD | 2-year PFS of 84% | 2-year OS of 93% |
| Bv57 | Bv monotherapy × 16 cycles with PET after 4 cycles | Unfit for chemo Stage IIB or bulky, stage III/IV | 38 (7 stage II) | 36 months | CMR 25.8% | Median PFS 7.3 months | Median OS 19.5 months |
| Bv- DTIC vs Bv - bendamustine44 | Bv-DTIC × 12 Bv-benda × 6* *closed early due to toxicity | Stages I-IV | 42 | 21.6 months | CMR Bv-DTIC 62% Bv-benda 88% | Median PFS 17.9 months | Not reached |
| Pembrolizumab followed by AVD51 | Pembro × 3 ⟶ AVD × 4-6 (4 cycles for early stage, 6 cycles for advanced-stage or early-stage bulky) | Stage I/II unfavorable Stage III/IV | 30 (4 pts >60) | 22.5 months | CMR 55% with pembro alone, but reached 100% after AVD × 2 | Median PFS not reached, 2-year PFS 100% | Median OS not reached, 2-year OS 100% |
| BV plus nivolumab58 | Bv-nivo every 21 days × 8 cycles | Stages I, II, III, IV, ≥60 years or <60 and unsuitable for standard chemo | 46 | 21.2 months | CMR 48% | Median PFS 18.3 months | Median OS not reached |
| Trial . | Trial design . | Disease stage . | N . | Median follow-up . | Outcomes . | PFS . | OS . |
|---|---|---|---|---|---|---|---|
| Pembrolizumab followed by AVD51 | Pembro × 3 ⟶ AVD × 4-6 (4 cycles for early stage, 6 cycles for advanced-stage or early-stage bulky) | Stage I/II unfavorable Stage III/IV | 30 | 22.5 months | CMR 55% with pembro alone, but reached 100% after AVD × 2 | Median PFS not reached, 2-year PFS 100% | Median OS not reached, 2-year OS 100% |
| Nivolumab and AVD54 | Nivo-AVD × 4 plus 30 Gy ISRT Sequential therapy: nivo × 4 doses ⟶ nivo-AVD × 2 ⟶ AVD × 2 plus 30 Gy ISRT | Early-stage unfavorable | 109 | 13 months | CMR Group 1: 83% Group 2: CR 84% | 12-month PFS: Group 1: 100% Group 2: 98% | 12-month OS 100% in both groups |
| Bv-AVD vs ABVD, followed by 30 Gy INRT53 | Bv-AVD × 4 or ABVD × 4 ⟶ 30 Gy INRT | Early-stage unfavorable | 170 | 45 months | CMR Bv-AVD 86.7% ABVD 78.9% | 2-year PFS: 97.3% with Bv-AVD vs 92.6% with ABVD | Median not reached |
| Bv-AD45 | Bv - AD × 2 ⟶ PET 1. If PET neg, then Bv - AD × 2 (total 4) 2. If PET pos, then Bv - AD × 4 (total 6) | Non-bulky early-stage favorable or unfavorable | 34 | 53 months | CMR 97% | Estimated 5-year PFS of 91% | Estimated 5-year OS of 96% |
| Bv-AVD +/- RT (4 cohorts)52 | BV-AVD × 4 ⟶ PET If PET neg, then 1. 30 Gy ISRT 2. 20 Gy ISRT 3. 30 consolidation volume radiotherapy 4. No radiotherapy | Early-stage unfavorable | 117 | 45.6 months | CMR 1. 93% 2. 100% 3. 93% 4. 97% | Overall 2-year PFS 94% 2-year PFS for 4 cohorts 1. 93.1% 2. 97% 3. 90% 4. 97% | Overall 2-year OS 99.1% |
| ABVD followed by Bv consolidation56 | ABVD × 2 ⟶PET Favorable and PET neg, then BV consolidation Favorable and PET pos or unfavorable and PET neg, then ABVD × 2 plus BV consolidation Unfavorable and PET pos, then ABVD × 4 plus BV consolidation | Nonbulky early-stage favorable and unfavorable | 41 | 47 months | CMR 95% | 3-year PFS of 92% 3-year PFS 100% for PET neg after Bv | OS was 97% 3 year OS 100% for PET neg after Bv |
| Trials with novel agents including patients older than 60 | |||||||
| Bv followed by AVD followed by Bv consolidation43 | Bv × 2 ⟶ AVD × 6 ⟶ Bv × 4 | Stage II-IV (age 60 or older) | 48 (9 stage II) | 23 months | CMR 90% after Bv-AVD | 2-year PFS of 84% | 2-year OS of 93% |
| Bv57 | Bv monotherapy × 16 cycles with PET after 4 cycles | Unfit for chemo Stage IIB or bulky, stage III/IV | 38 (7 stage II) | 36 months | CMR 25.8% | Median PFS 7.3 months | Median OS 19.5 months |
| Bv- DTIC vs Bv - bendamustine44 | Bv-DTIC × 12 Bv-benda × 6* *closed early due to toxicity | Stages I-IV | 42 | 21.6 months | CMR Bv-DTIC 62% Bv-benda 88% | Median PFS 17.9 months | Not reached |
| Pembrolizumab followed by AVD51 | Pembro × 3 ⟶ AVD × 4-6 (4 cycles for early stage, 6 cycles for advanced-stage or early-stage bulky) | Stage I/II unfavorable Stage III/IV | 30 (4 pts >60) | 22.5 months | CMR 55% with pembro alone, but reached 100% after AVD × 2 | Median PFS not reached, 2-year PFS 100% | Median OS not reached, 2-year OS 100% |
| BV plus nivolumab58 | Bv-nivo every 21 days × 8 cycles | Stages I, II, III, IV, ≥60 years or <60 and unsuitable for standard chemo | 46 | 21.2 months | CMR 48% | Median PFS 18.3 months | Median OS not reached |
ABVD, doxorubicin hydrochloride, bleomycin, vinblastine sulfate, dacarbazine (DTIC); Bv, brentuximab vedotin; CMR, complete metabolic response; INRT, involved nodal radiotherapy; ISRT, involved site radiotherapy; OS, overall survival; PFS, progression free survival.