Table 1.
Summary of phase I, II and III trials and retrospective studies in Hodgkin Lymphoma.
| Trial | Design | Study population | Study arms | Outcome |
|---|---|---|---|---|
| Frontline | ||||
| NU16H08 [74] | Phase II |
> 18 years N = 30 |
PEM followed by AVD |
After PEM: 37%, CMR 25%, >90% decrease MTV on PET-CT After AVD: All, CMR |
| NIVAHL [23] | Phase II |
18–60 years N = 110 |
Arm A: Nivo+AVD x4 Arm B: Nivo x4 then Nivo+AVD x2 then AVD x2 |
ORR: Arm A: 100%, B: 96% CR: Arm A: 81%, B: 86% 1-year PFS: 98% 1-year OS: 100% |
| Trial of the LYSA group [28] | Phase II |
> 60 years N = 89 |
PVAB x6 |
CMR: 77% 2-year OS: 84% 2-year PFS: 61% |
| HD14 [12] | Randomized parallel arm trial |
< 60 years Early stage, unfavourable N = 1112 |
BEACOPP x2 then ABVD x2 Or ABVD x4 |
10-years PFS: 91.2 vs 85.6%, p < 0.0001 10-years OS: 94% vs 94.1 |
| NCT01716806 [41] | Phase II |
> 60 years N = 19 |
BV + Nivo < 16 cycles | ORR: 100%, CR rate: 72%, PR rate: 28% |
| Salvage therapy | ||||
| Stamatoullas et al. [35] | Phase I/II | N = 42 | BV-ICE x2 then if CMR BV-ICE x1 then BV x1 then ASCT |
CMR: 69.2%, PR: 25.6% 1-year PFS: 69% |
| Herrera et al. [36] | Phase II | N = 39 |
Nivo x6 If CR - > ASCT If no CR - > Nivo-ICE x2 |
1-year OS: 97% 1-year PFS: 79% |
| Moskowitz et al. [37] | Phase II | N = 39 | PEM-GVHD x2-4 then ASCT |
ORR: 100%, CR rate: 95%, PR rate: 5% No relapse or death (median follow-up 11.2 months) |
| Herrera et al. [39, 40] | Phase I/II |
≥18 years N = 61 |
BV + Nivo x4 +/- ASCT |
ORR: 85%, CR: 67% 2-year PFS: 78% (if ASCT, 91%) 2-year OS: 93% |
| LaCasce [38] | Phase I/II | N = 53 | BvB <6 cycles then ASCT or BV x14 |
CR: 95% (if ASCT, 94%) 2-year PFS: 69.8% (if ASCT, 63%) |
| Checkmate 205 [75] | Phase II | N = 276 |
Nivo after ASCT Cohort A: BV naïve N = 60 Cohort B: Failure of BV post-ASCT N = 60 Cohort C: After BV before and/or after ASCT failure |
ORR/CR: Overall: 69%/16% Cohort A: 65%/29% Cohort B: 68%/13% Cohort C: 73%/12% Median PFS: Overall: 14.7 m Cohort A: 18.3 m Cohort B: 14.7 m Cohort C: 11.9 m |
| Primary refractory disease | ||||
| KEYNOTE-024 [58] | Phase III |
≥18 years N = 304 |
PEM vs BV | mPFS: 13.2 vs 8.3 m |
| CPI before allo-HCT | ||||
| Merryman et al. [62, 76] | Retrospective |
Pts treated with anti-PD1 mAb before transplant N = 150 |
TT: Nivo N = 118, PEM N = 31, avelumab N = 1 Transplant: Haplo (47%), MSD (19%), MUD (26%), MMUD (5%), CB (1%), unknown (1%) |
2-year PFS: 65% 2-year OS: 79% 2-year NRM: 14% 6-m CI of grade 2-4 aGVHD: 39% 6-m CI of grade 3-4 aGVHD: 16% 2-year CI of cGVHD: 45% |
| Manson et al. [62] | Retrospective |
Pts treated with Nivo with a cohort of allo-SCT N = 17 |
TT: Nivo Transplant |
1-year PFS: 76% 1-year OS: 82% 1-year TRM: 17.6% Grade 2-4 aGVHD: 82% cGVHD: 29% |
| El Cheikh et al. [77] | Retrospective |
Nivo followed by allo-SCT N = 9 |
TT: Nivo N = 9 Transplant: Haplo (67%) MSD (33%) |
Grade 2-4 aGVHD: 100% cGVHD: 33% |
| CPI for relapse after allo-HCT | ||||
| Herbaux et al. [69] | Retrospective |
Relapse after allo-SCT N = 20 |
Nivo |
ORR: 95%, CR: 42%, PR: 52% 1-year PFS: 58% 1-year OS:79% GvHD: 30% of pts |
| Haverkos et al. [70] | Retrospective |
Relapse after allo-SCT N = 31 |
Nivo or PEM | GvHD: 55% of pts (59% aGvHD, 41% cGvHD) |
| Ibrutinib for relapse after allo-SCT | ||||
| Badar et al. [71] | Retrospective |
≥18 years N = 7 |
Ibrutinib | ORR: 57%, CR: 43%, PR: 14% |
PEM pembrolizumab, AVD Adriamycin, Vincristine, Dacarbazine, CMR complete metabolic response, MTV metabolic tumour volume, PET-CT positron emission tomography/computed tomography, Nivo Nivolumab, PFS progression free survival, OS overall survival, PVAB prednisone, vinblastine, doxorubicin and bendamustine, ABVD Adriamycin, Bleomycin, Vincristine, Dacarbazine, BV brentuximab vedotin, ORR overall response rate, CR complete response, PR partial response, ICE ifosfamide, mesna, carboplatin, etoposide, ASCT autologous stem cell transplantation, BvB brentuximab vedotin, bendamustin, mPFS median progression free survival, m months, CPI check point inhibitors, allo-HCT allogeneic hematopoietic stem cell transplantation, TT treatment, Haplo haploidentical transplant, MSD matched sibling donor, MUD matched unrelated donor, MMUD mismatched unrelated donor, CI cumulative incidence, GVHD graft versus host disease, aGVHD acute GVHD, cGVHD chronic GVHD, pts patients, eBEACOPP bleomycin, etoposide, doxorubicin (aka adriamycin), cyclophosphamide, vincristine (aka oncovin), procarbazine, prednisolone.