Studies (completed and ongoing) of brentuximab vedotin, as a single agent or in combination, in CD30-expressing mature T-cell neoplasms
| Studies . | Treatment . | Setting . | Study design . | No. patients . | PTCL subtypes . | Definition CD30+, % . | ORR . | CR rate . | OS . | PFS . |
|---|---|---|---|---|---|---|---|---|---|---|
| Completed | ||||||||||
| Younes et al46 ,* | Single-agent BV (0.1-3.6 mg/kg every 3 wk) | RR CD30+ malignancies | Phase 1, multicenter | 3* | sALCL (n = 2), AITL (n = 1) | ND | sALCL, 100%; AITL, 0% | sALCL, 100%; AITL, 0% | NR | NR |
| Pro et al47,48 | Single-agent BV (1.8 mg/kg every 3 wk) | RR sALCL | Phase 2, multicenter | 58 | sALCL (n = 58; 72% ALK−) | ND | 86% (range, 74.6-93.9) | 57% (range, 43.2-69.8) | 5-y, 60% | 5-y, 39% |
| Horwitz et al49 | Single-agent BV (1.8 mg/kg every 3 wk) | RR PTCL | Phase 2, multicenter | 35 | PTCL-NOS (n = 22), AITL (n = 13) | ≥1 | PTCL-NOS, 33% (range, 15-57); AITL, 54% (range, 25-81) | NR | mPFS: PTCL-NOS, 1.6 mo; AITL, 6.7 mo | |
| Fanale et al50,51 | (A) BV × 2 followed by CHOP; (B) BV-CHP. | Upfront CD30+ PTCL | Phase 1, multicenter | 39 | (A) ALCL (n = 13, 100%); (B) sALCL (n = 19, 73%; n = 6 ALK+) and non-ALCL (n = 7; 27%)† | ≥1 | (A) 85%; (B) 100% both sALCL and non-ALCL | (A) 62%; (B) sALCL, 84%; non-ALCL, 100% | (A) 1-y, 85%; (B) 5-y, 80% (sALCL, 79%; non-ALCL, 83%) | (A) 1-y, 77%; (B) 5-y, 52% (sALCL, 47%; non-ALCL, NE) |
| Horwitz et al52 | BV-CHP vs CHOP | Upfront CD30+ PTCL | Phase 3, randomized, double blind | 226 both arms (N = 452 total) | BV-CHP: sALCL, n = 162 (68%); non-ALCL, n = 64 (32%).‡ CHOP: sALCL, n = 154 (72%); non-ALCL, n = 72 (28%)§ | ≥10 | BV-CHP, 83% vs CHOP, 72% | BV-CHP, 68% vs CHOP, 56% | Median OS, NR vs 17.5 mo (HR, 0.66) | mPFS: BV-CHP, 48.0 mo vs CHOP, 20.8 mo (HR, 0.71) |
| Ongoing | ||||||||||
| NCT03496779 | Gemcitabine → BV maintenance | RR CD30+ PTCL | Phase 2, multicenter | 70 | ≥5 | |||||
| NCT03217643 | BV-CHP followed by ASCT | Upfront EATL, type 1 | Phase 2, single center | 25 | ≥10 | |||||
| NCT02588651 | Single-agent BV | RR CD30-low PTCL | Phase 2, multicenter | 31 | <10 | |||||
| NCT03409432 | BV + lenalidomide | RR PTCL | Phase 2, single center | 37 | 0-100 | |||||
| NCT03113500 | BV-CHEP → BV maintenance | Upfront PTCL | Phase 2, multicenter | 40 | ≥1 | |||||
| NCT02499627 | BV + bendamustine | RR HL and PTCL | Phase 2, multicenter | 60 | ND | |||||
| NCT03264131 | BV-CHEP → BV maintenance vs alloHCT | Upfront ATLL | Phase 2, multicenter | 28 | ND | |||||
| NCT03246750 | BV-MAD | Upfront ENKTCL | Phase 2, multicenter | 36 | ND |
| Studies . | Treatment . | Setting . | Study design . | No. patients . | PTCL subtypes . | Definition CD30+, % . | ORR . | CR rate . | OS . | PFS . |
|---|---|---|---|---|---|---|---|---|---|---|
| Completed | ||||||||||
| Younes et al46 ,* | Single-agent BV (0.1-3.6 mg/kg every 3 wk) | RR CD30+ malignancies | Phase 1, multicenter | 3* | sALCL (n = 2), AITL (n = 1) | ND | sALCL, 100%; AITL, 0% | sALCL, 100%; AITL, 0% | NR | NR |
| Pro et al47,48 | Single-agent BV (1.8 mg/kg every 3 wk) | RR sALCL | Phase 2, multicenter | 58 | sALCL (n = 58; 72% ALK−) | ND | 86% (range, 74.6-93.9) | 57% (range, 43.2-69.8) | 5-y, 60% | 5-y, 39% |
| Horwitz et al49 | Single-agent BV (1.8 mg/kg every 3 wk) | RR PTCL | Phase 2, multicenter | 35 | PTCL-NOS (n = 22), AITL (n = 13) | ≥1 | PTCL-NOS, 33% (range, 15-57); AITL, 54% (range, 25-81) | NR | mPFS: PTCL-NOS, 1.6 mo; AITL, 6.7 mo | |
| Fanale et al50,51 | (A) BV × 2 followed by CHOP; (B) BV-CHP. | Upfront CD30+ PTCL | Phase 1, multicenter | 39 | (A) ALCL (n = 13, 100%); (B) sALCL (n = 19, 73%; n = 6 ALK+) and non-ALCL (n = 7; 27%)† | ≥1 | (A) 85%; (B) 100% both sALCL and non-ALCL | (A) 62%; (B) sALCL, 84%; non-ALCL, 100% | (A) 1-y, 85%; (B) 5-y, 80% (sALCL, 79%; non-ALCL, 83%) | (A) 1-y, 77%; (B) 5-y, 52% (sALCL, 47%; non-ALCL, NE) |
| Horwitz et al52 | BV-CHP vs CHOP | Upfront CD30+ PTCL | Phase 3, randomized, double blind | 226 both arms (N = 452 total) | BV-CHP: sALCL, n = 162 (68%); non-ALCL, n = 64 (32%).‡ CHOP: sALCL, n = 154 (72%); non-ALCL, n = 72 (28%)§ | ≥10 | BV-CHP, 83% vs CHOP, 72% | BV-CHP, 68% vs CHOP, 56% | Median OS, NR vs 17.5 mo (HR, 0.66) | mPFS: BV-CHP, 48.0 mo vs CHOP, 20.8 mo (HR, 0.71) |
| Ongoing | ||||||||||
| NCT03496779 | Gemcitabine → BV maintenance | RR CD30+ PTCL | Phase 2, multicenter | 70 | ≥5 | |||||
| NCT03217643 | BV-CHP followed by ASCT | Upfront EATL, type 1 | Phase 2, single center | 25 | ≥10 | |||||
| NCT02588651 | Single-agent BV | RR CD30-low PTCL | Phase 2, multicenter | 31 | <10 | |||||
| NCT03409432 | BV + lenalidomide | RR PTCL | Phase 2, single center | 37 | 0-100 | |||||
| NCT03113500 | BV-CHEP → BV maintenance | Upfront PTCL | Phase 2, multicenter | 40 | ≥1 | |||||
| NCT02499627 | BV + bendamustine | RR HL and PTCL | Phase 2, multicenter | 60 | ND | |||||
| NCT03264131 | BV-CHEP → BV maintenance vs alloHCT | Upfront ATLL | Phase 2, multicenter | 28 | ND | |||||
| NCT03246750 | BV-MAD | Upfront ENKTCL | Phase 2, multicenter | 36 | ND |
alloHCT, allogeneic hematopoietic cell transplant; BV, brentuximab vedotin; BV-CHEP, BV in combination with cyclophosphamide, doxorubicin, etoposide, and prednisone; BV-CHP, BV in combination with cyclophosphamide, doxorubicin, and prednisone; BV-MAD, BV in combination with methotrexate, L-asparaginase, and dexamethasone; CR, complete response; ENKTCL, extranodal natural killer/T-cell lymphoma; HR, hazard ratio; mPFS, median PFS; ND, not defined; NE, not estimable; NR, not reported; ORR, overall response rate; RR, relapsed and/or refractory; sALCL, systemic ALCL.
Eligible patients included those with any CD30+ lymphoma; a total of 45 patients was enrolled, but only the outcomes for subjects with PTCL are reported.
PTCL-NOS, n = 2; angioimmunoblastic T-cell lymphoma, n = 2; enteropathy-associated T-cell lymphoma, n = 1; adult T-cell leukemia/lymphoma, n = 2.
Non-ALCL: PTCL-NOS, 13% (n = 29); AITL, 13% (n = 30); ATLL, 2% (n = 4); EATL, <1% (n = 1).
Non-ALCL: PTCL-NOS, 19% (n = 43); AITL, 11% (n = 24); ATLL, 1% (n = 3); EATL, 1% (n = 2).