Background
CD30-targeted therapy
Monoclonal antibodies and mAb-immunotoxin conjugates
Brentuximab vedotin
Therapy for relapsed or refractory disease
Study | Phase |
N
| Setting | Treatment | Efficacy results |
---|---|---|---|---|---|
Younes et al. 2010 [11] | 1 | 42 | Relapsed or refractory | Bv 0.1 to 3.6 mg/kg Q3W MTD 1.8 mg/kg | All patients: ORR 36% (CR 21%, PR 14%) MTD only (n = 12): ORR 50% (CR 33%, PR 17%) |
Fanale et al. 2012 [12] | 1 | 38 | Relapsed or refractory | Bv 0.4 to 1.4 mg/kg on days 1, 8, and 15 of each 28-day cycle MTD 1.2 mg/kg | All evaluable (n = 35): ORR 54% (CR 29%, PR 26%) MTD only (n = 12): ORR 58% (CR 25%, PR 33%) |
2 | 102 | Relapsed or refractory after ASCT | Bv 1.8 mg/kg Q3W for up to 16 cycles | ORR 75% (CR 34%, PR 40%) Median DOR 20.5 months (CR patients) 3-year follow-up: Median PFS 9.3 months, median OS 40.5 months 5-year follow-up: 5-year PFS rate 22%, 5-year OS rate 41% | |
O’Connor et al. 2018 [19] | 2 | 37 | Relapsed or refractory | Bv 1.8 mg/kg day 1 and bendamustine 90 mg/m2 day 1–2 Q3W for up to 6 cycles | ORR 78% (CR 43%, PR 35%) Median PFS and median OS not reached |
Moskowitz et al. 2015 (AETHERA) [21] | 3 | 329 | Consolidation after ASCT | Bv 1.8 mg/kg vs placebo Q3W for 16 cycles | Bv (n = 165) vs placebo (n = 164): Median PFS 42.9 vs 24.1 months (HR = 0.57, P = 0.0013) |
2 | 37 | Relapsed after or refractory to frontline therapy | Bv 1.8 mg/kg Q3W for 4 cycles | ORR 68% (CR 35%, PR 32%) 18 patients directly proceeded to ASCT; 18 patients received additional salvage chemotherapy and 15 proceeded to ASCT 18-month post-transplant PFS rate 73% | |
Moskowitz et al. 2015 [24] | 2 | 45 | Relapsed after or refractory to frontline therapy | Bv 1.2 mg/kg days 1, 8, 15 Q4W for 2 cycles | 12 (27%) were PET negative and proceeded to ASCT; 32 received additional salvage chemotherapy and proceeded to ASCT 2-year EFS rate 80%, 2-year OS rate 95% |
Cassaday et al. 2017 [25] | 1/2 | 24 | Relapsed after or refractory to frontline therapy | Bv 1.2 or 1.5 mg/kg days 1, 8 Q3W in combination with ICE for 2 cycles | 20 (87%) of 23 evaluable patients achieved PET CR 19 had undergone ASCT |
Garcia-Sanz et al. 2016 [26] | 2 | 66 | Relapsed after or refractory to frontline therapy | Bv 1.8 mg/kg Q3W in combination with ESHAP for 3 cycles | Pre-ASCT ORR 96% (CR 70%, PR 26%) 61 had undergone an ASCT Projected 1-year post-transplant PFS rate 87%, OS rate 90% |
LaCasce et al. 2015 [27] | 1/2 | 53 | Relapsed after or refractory to frontline therapy | Bv 1.8 mg/kg Q3W plus bendamustine 90 mg/m2 days 1–2 Q3W for up to 6 cycles | ORR 93% (CR 74%, PR 19%) 37 had undergone ASCT Estimated 12-month PFS rate 80% |
1 | 51 | Newly diagnosed stage IIA bulky disease or stage IIB–IV | Bv 0.6, 0.9, or 1.2 mg/kg Q2W in combination with ABVD or AVD for up to 6 cycles (28-day) | Bv+ABVD arm (n = 25, dose escalation): CR 95% 5-year FFS rate 79%, OS rate 92% Bv+AVD arm (n = 26, 1.2 mg/kg only): CR 96% 5-year FFS rate 92%, OS rate 100% | |
Connors et al. 2018 (ECHELON-1) [31] | 3 | 1334 | Untreated stage III or IV | Bv 1.2 mg/kg Q2W in combination with AVD vs ABVD, for up to 6 cycles (28-day) | Bv+AVD vs ABVD: ORR 86 vs 83% CR 73 vs 70% 2-year modified PFS rate 82.1 vs 77.2% (HR = 0.77, P = 0.03) |
Abramson et al. 2015 [33] | 2 | 34 | Newly diagnosed non-bulky stage I–II | Bv 1.2 mg/kg Q2W for 1 cycle (28-day), followed by Bv+AVD for 4–6 cycles (28-day) | After first cycle of Bv: CR 53% After 2 cycles of Bv+AVD: CR 97% At the end of treatment: CR 88% PFS rate 90% and OS rate 97% (median follow-up 14 months) |
Kumar et al. 2016 [34] | 2 | 30 | Newly diagnosed stage I–II with unfavorable risk factors | Bv 1.2 mg/kg Q2W in combination with AVD for 4 cycles (28-day), followed by 30 Gy ISRT if PET negative | After 2 cycles: 90% PET negative After 4 cycles: 93% PET negative 1-year PFS rate 93.3% |
Evens et al. 2017 [37] | 2 | 48 | Newly diagnosed stage IIB–IV, age ≥ 60 years | Bv 1.8 mg/kg Q3W for 2 cycles, followed by AVD for 6 cycles, followed by 4 more cycles of Bv if responded | For evaluable patients (n = 41) After 2 cycles of Bv: ORR 87% (CR 30%) After completion of AVD: ORR 95% (CR 90%) At end of therapy: ORR 95% (CR 93%) 2-year PFS rate 90% |
2 | 41 | Untreated limited stage non-bulky | ABVD for 2–6 cycles, followed by Bv 1.8 mg/kg Q3W for 6 cycles | After 2 cycles of ABVD: 72% PET negative After completion of Bv: 90% PET negative Estimated 2-year PFS rate 92%, OS rate 97% | |
Federico et al. 2016 [40] | 2 | 12 | Untreated stages IA, IIA, and IIIA | Bv 1.8 mg/kg for 2 cycles, followed by ABVD for 3 or 6 cycles, and radiation therapy if indicated | After 2 cycles of Bv: ORR 92% (CR 83%, PR 8%) At the end of therapy: ORR 100% (CR 92%, PR 8%) 1-year PFS rate 92% |
Eichenauer et al. 2017 [41] | 2 | 104 | Newly diagnosed advanced stage | Bv 1.2 mg/kg plus ECAPP or ECADD for 6 cycles (21-day) | Bv+ECAPP arm (49 evaluable): CR 86%, 18-month PFS rate 95% Bv+ECADD arm (52 evaluable): CR 88%, 18-month PFS rate 89% |
Friedberg et al. 2017 [42] | 2 | 42 | Treat-naïve, age ≥ 60 years, ineligible for or declined standard frontline chemotherapies | Bv 1.8 mg/kg plus dacarbazine 375 mg/m2 Q3W for 12 cycles followed by Bv 1.8 mg/kg for 4 cycles or more, or Bv 1.8 mg/kg day 1 plus bendamustine 90 mg/m2 days 1–2 Q3W for 6 cycles followed by Bv 1.8 mg/kg for 10 cycles or more | Bv+dacarbazine arm (21 evaluable): ORR 100% (CR 62%, PR 38%) Median PFS 17.9 months Bv + bendamustine arm (20 evaluable): ORR 100% (CR 88%, PR 12%) Median PFS not reached |
Forero-Torres et al. 2015 [44] | 2 | 27 | Treat-naïve, age ≥ 60 years, ineligible for or declined conventional combination treatment | Bv 1.8 mg/kg Q3W for up to 16 cycles; additional cycles allowed in those with clinical benefit | ORR 92% (CR 73%, PR 19%) Median PFS 10.5 months |
Gibbs et al. 2017 (BREVITY) [45] | 2 | 38 | Untreated, unfit for standard treatment | Bv 1.8 mg/kg Q3W for up to 16 cycles | For evaluable patients (n = 31): CMR after 4 cycles 26% ORR 84% Median PFS 7.4 months |
Consolidation therapy after ASCT
Salvage therapy after frontline therapy
Frontline therapy
Bispecific antibodies
CD30 CAR-T cells
PD-1-targeted immunotherapy
Study | Trial name | Phase |
N
| Setting | Treatment | Efficacy results |
---|---|---|---|---|---|---|
Ansell et al. 2015 [52] | CheckMate 039 (arm 1, expansion cohort) | 1 | 23 | Relapsed or refractory | Nivolumab 3 mg/kg Q2W for up to 2 years | ORR 87% (CR 17%, PR 70%) PFS rate at 24 weeks 86% |
CheckMate 205 (cohort B) | 2 | 80 | Relapsed or refractory after ASCT and brentuximab vedotin | Nivolumab 3 mg/kg Q2W | ORR 68% (CR 13%, PR 55%) 12-month PFS rate 54.6%, OS rate 94.9% Median PFS 14.7 months | |
Armand et al. 2018 [56] | CheckMate 205 (cohorts A and C) | 2 | Cohort A: 63 Cohort C: 100 | Cohort A: relapsed or refractory, brentuximab vedotin naïve Cohort C: relapsed or refractory after brentuximab vedotin | Nivolumab 3 mg/kg Q2W | Cohort A: ORR 65% (CR 29%) Median DOR 20.3 months Median PFS 18.3 months Cohort C: ORR 73% (CR 12%) Median DOR 14.5 months Median PFS 11.9 months |
Herbaux et al. 2017 [58] | 20 | Relapsed after Allo-SCT | Nivolumab 3 mg/kg Q2W | ORR 95% (CR 42%, PR 52%) 1-year PFS rate 58.2%, OS rate 78.7% | ||
Ramchandren et al. 2017 [59] | CheckMate 205 (cohort D) | 2 | 51 | Newly diagnosed advanced stage | Nivolumab 240 mg biweekly for 4 doses, followed by nivolumab plus AVD for 6 cycles | ORR 84% (CR 80%, PR 4%) Modified PFS rate at 9 months 94% |
Ansell et al. 2016 [60] | CheckMate 039 (arm 2) | 1 | 31 | Relapsed or refractory | Nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W for 4 cycles, followed by nivolumab 3 mg/kg Q2W for up to 2 years | ORR 74% (CR 19%, PR 55%) |
Herrera et al. 2017 [62] | 1/2 | 62 | Relapsed after or refractory to frontline therapy | Nivolumab 3 mg/kg plus brentuximab vedotin 1.8 mg/kg Q3W for up to 4 cycles | ORR 83% (CR 62%) | |
KEYNOTE-013 | 1b | 31 | Relapsed or refractory after brentuximab vedotin | Pembrolizumab 10 mg/kg Q2W for up to 2 years | ORR 65% (CR 16%, PR 48%) median PFS 11.4 months 6-month PFS rate 66%, OS rate 100% 12-month PFS rate 48%, OS rate 87% | |
Chen et al. 2017 [65] | KEYNOTE-087 | 2 | 210 | Relapsed or refractory after ASCT and/or brentuximab vedotin | Pembrolizumab 200 mg Q3W for up to 2 years | ORR 69.0% (CR 22.4%, PR 46.7%) 6-month PFS rate 72.4%, OS rate 99.5% 9-month PFS rate 63.4%, OS rate 97.5% |