Table 3 Novel targeted post-ASCT consolidative options in development or approved for use in R/R HL
Targeted agent | Treatment setting | Efficacy | Safety |
|---|---|---|---|
ADCs | |||
Brentuximab vedotin (anti-CD30; monotherapy) | Consolidation therapy after ASCT in patients with HL at high risk of progression or relapse (n = 165 brentuximab vedotin arm) | • 2-year PFS rate: 63% • 5-year PFS rate: 59% | • Grade 3/4 AEs: 16% • Peripheral neuropathy: 67% (90% of which had improved or completely resolved after 5 years’ follow-up) |
Camidanlumab tesirine (anti-CD25; monotherapy) phase I study (NCT00516217) [66] | R/R HL (median 5 prior lines; n = 26) | • ORR 81% • CR 50% | • Grade ≥ 3 treatment-emergent adverse events: 62% |
Histone deacetylase inhibitors | |||
Panobinostat (monotherapy) phase III (NCT01034163) [67] | Consolidation therapy after HDC and ASCT in patients with HL at high risk of relapse (n = 27 panobinostat arm) | Study discontinued early due to poor accrual (41/367 planned patients enrolled), so efficacy not formally evaluated | • Grade 3/4 AEs: 65%. Most frequent: - Neutropenia (27%) - Thrombocytopenia (15%) - Diarrhea, vomiting, fatigue (12%) |
Monoclonal antibodies | |||
Nivolumab (anti-PD-1; monotherapy) phase II CheckMate 205 study (NCT02181738) [68, 69] | R/R cHL after ASCT and brentuximab vedotin | • ORR 69% | • Grade 3/4 AEs were low |
Pembrolizumab (anti-PD-1; monotherapy) (NCT02362997) [70] | Post-ASCT consolidation therapy in patients with R/R cHL who had achieved a CR or PR with salvage chemotherapy (N = 31) | • PFS rate at 18 months: 82% • OS rate at 18 months: 100% | • Grade ≥ 2 AEs: 80% • Grade ≥ 3 AEs: 30% • Immune-related AEs: 43% |
Galiximab (anti-CD80) phase II CALGB 50602 study (NCT00516217) [71] | R/R HL; median 3 prior regimens (n = 29) | • ORR 10.3% • Median PFS 1.6 months | • Minimal grade 3/4 toxicities |
Lucatumumab (anti-CD40) phase Ia/II study (NCT00670592) [72] | R/R HL (n = 37) | • ORR 13.5% | • Grade 3/4 AEs: 65% (HL and NHL) |
TNX-650 (anti-IL-13) phase I/II study (NCT00441818) | Refractory HL | • Study in progress | |
Relatlimib (anti-LAG-3) phase I/II study with/without nivolumab (NCT02061761) | R/R HL | • Study in progress | |
AMG655 (anti-TRAIL) with bortezomib or vorinostat phase Ib study (NCT00791011) | R/R Lymphoma | • No longer in development | |
RFT5-SPMT-dgA (anti-CD25) | R/R HL | • No longer in development | |
Alemtuzumab (anti-CD52) phase II study with dose-adjusted-EPOCH regimen (NCT01030900) | R/R HL | • Study in progress (monotherapy failed) | |
Bispecific antibody | |||
AFM13 (anti-CD30/CD16a; monotherapy) phase I study complete; phase II ongoing (NCT02321592) [73] | Heavily-pretreated R/R HL (n = 28) | • ORR 11.5% | • Grade ≥ 3 AEs: 29% |
AFM13 (anti-CD30/CD16a; plus pembrolizumab) phase Ib KEYNOTE-206 study (NCT02665650) [74] | R/R HL (failed brentuximab vedotin; n = 30) | • ORR 88% • CR 46% • 6-month PFS 77% | • Grade 3/4 AEs included infusion-related reactions in 13% |
CAR-T cells | |||
Anti-CD30 RELY-30 phase I study (NCT02917083) [75] | R/R HL Median 5 prior therapies (n = 14) | • CR 58% | • Not reported |
Phase Ib/II study [76] | R/R HL Median 7.5 prior therapies (n = 22) | • CR 53% | • Not reported |
Phase I study (NCT02259556) [77] | R/R HL Heavily pretreated patients (n = 18) | • ORR 39% • Median PFS 6 months | • Grade ≥ 3 AEs in 2 patients |
Anti-LMP1/2 phase I study (NCT00671164) [78] | R/R HL/NHL (n = 25) | • 2-year EFS 50% • ORR 62% • CR 52% | • Not reported |