Table 1 Major clinical trials on brentuximab vedotin for treatment of Hodgkin lymphoma

Younes et al. 2010 [11]

1

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

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%)

Younes et al. 2012 [14,15,16]

2

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

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

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)

Chen et al. 2015 [22, 23]

2

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

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

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

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

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%

Younes et al. 2013 [29, 30]

1

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

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

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

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

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%

Park et al. 2016 [38, 39]

2

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

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

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

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

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

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