From: Advances in CD30- and PD-1-targeted therapies for classical Hodgkin lymphoma
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 1.8Â mg/kg Q3W for up to 16Â cycles | ORR 75% (CR 34%, PR 40%) Median DOR 20.5Â months (CR patients) 3-year follow-up: Median PFS 9.3Â months, median OS 40.5Â 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 1.8Â mg/kg Q3W for 4Â 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 1.2Â mg/kg days 1, 8, 15 Q4W for 2Â 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 1.5Â mg/kg days 1, 8 Q3W in combination with ICE for 2Â 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 1.8Â mg/kg Q3W in combination with ESHAP for 3Â 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 1.8Â mg/kg for 2Â cycles, followed by ABVD for 3 or 6Â cycles, and radiation therapy if indicated | After 2Â 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 1.2Â mg/kg plus ECAPP or ECADD for 6Â 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 |