Novel Salvage Therapy Options for Initial Treatment of Relapsed/Refractory Classical Hodgkin’s Lymphoma: So Many Options, How to Choose?
Abstract
:Simple Summary
Abstract
1. Background
2. Salvage Chemotherapy
3. Brentuximab Vedotin
Regimen | Trial | Inclusion | # Pts | ORR % | CR % | mPFS or PFS | OS % | Toxicity |
---|---|---|---|---|---|---|---|---|
BV-post ASCT | Younes [25] Chen [26] | R/R after ≥1 line therapy and ASCT | 102 | 75 | 34 | 9.3 mo | 5Y: 41 | Any grade neuropathy (15%) Nausea (35%) |
BV-pre ASCT | Chen et al. [27] | R/R HL after 1 line therapy | 37 | 68 | 35 | G3 neutropenia (5%) G1 neuropathy (49%) Rash (40%) | ||
BV → aug ICE pre ASCT | Moskowitz [29,30] | R/R after ≥1 line therapy | 65 | 76 | 76 | 6Y: 73% | 2Y: 95 6Y: 86 | G1–2 neuropathy (49%) |
BV → salvage pre ASCT | Herrera [28] | R/R HL after 1 line therapy | 56 | 75 | 43 | 2Y: 67% | 2Y: 93 | Any grade neuropathy (63%) * Any grade rash (50%) * |
BV + benda | LaCasce [31,32] | R/R HL after 1 line therapy | 53 | 93 | 74 | 2Y: 63% 3Y: 60% | 3Y: 92 | Infusion reactions (56%) Any grade neuropathy (54%) G3 Neuropathy (3.6%) |
BV + benda ** | O’Connor [33] | R/R HL after ≥ line therapy | 65 | 71 | 32 | G3–4 Neutropenia (25%) G3 lung infection (14%) | ||
BV + benda | Kalac [34] | Refractory after ≥1 line therapy + 90% prior auto | 10 | 100 | 90 | |||
BV + benda *** | Picardi [35] | R/R after ≥1 line therapy + 25% ASCT | 20 | 100 | 100 | 2Y: 94% | G3–4 Neutropenia (15%) CMV viremia (25%) | |
BV + benda | Broccoli [36] | 1st salvage No prior txp | 40 | 84 | 79 | 3Y:67% | 3Y: 88 | G3–4 Neutropenia (27%) Any grade skin rxn (28%) G1 neuropathy (1.8%) |
BV + benda − retrospective | Iannitto [37] | Refractory or 2nd relapse HL; 25% txp | 47 | 79 | 49 | 18 mo | 2Y: 72 | G3–4 Neutropenia (23%) G3–4 Neuropathy (11%) |
BV + ICE × 2 | Cassaday [38] | 1st salvage or primary refractory | 23 | 87 | G3–4 Sepsis/Neutropenic Fever (48%) Any grade neuropathy (30%) G3 neuropathy (4.3%) | |||
BV + ICE × 2–3 | Stamatoullas [39] | R/R after 1 line therapy | 39 | 69 | 1Y: 69% | G3–4 Hematologic Toxicity (71%) G3–4 Infection (21%) | ||
Dose-dense BV + ICE | Lynch [40] | R/R after 1 line therapy; no prior txp | 45 | 91 | 74 | G3–4 Neutropenia (73%) G3–4 Thrombocytopenia (80%) Sepsis (13%) G3 neuropathy (2%) | ||
BV + DHAP | Hagenbeek [41] Kersten [42] | R/R after 1 line therapy | 52 | 81 | 2Y: 74% | 2Y: 95 | G3–4 Neutropenia (65%) G3–4 Thrombocytopenia (76%) G3–4 infections (30%) | |
BV + ESHAP | Garcia-Sanz [43] | R/R after 1 line therapy | 66 | 91 | 70 | G3–4 neutropenia (32%) G3–4 thrombocytopenia (21%) | ||
Summary of Trials with Immunotherapy-based Agents in Relapsed/Refractory cHL. | ||||||||
Nivolumab | Ansell [44] | R/R after ≥1 line therapy (BV/chemo/ASCT) | 23 | 87 | 17 | Any grade rash (22%) Any grade thrombocytopenia (17%) Pancreatitis (4%) | ||
Nivolumab | Younes [45] | R/R after BV and ASCT | 80 | 66 | 9 | G1–2 fatigue (25%) G1–2 infusion-related rxn (20%) Any grade rash (16%) Pneumonitis (3%) | ||
Nivolumab | Armand [46] | R/R after ASCT; BV naïve, BV after ASCT, BV before/after ASCT | 243 | 69 | 14.7 mo | Any grade fatigue (23%) Diarrhea (15%) G3–4 elevated lipase (5%) G3–4 neutropenia (3%) | ||
Pembrolizumab | Chen [47,48] | R/R post-ASCT + BV, chemo-resistant w/o ASCT, ASCT-BV | 210 | 72 | 28 | 13.7 mo | G3 Neutropenia (2.4%) G3 Diarrhea (1.4%) | |
BV + Nivolumab | Advani [49] | R/R after 1 line therapy (pre ASCT) | 91 | 85 | 67 | 3Y: 91% | G4 Pneumonitis (3%) G3–4 Neutropenia (5%) Guillain Barre syndrome (1%) | |
BV + Nivolumab + Ipilimumab | Diefenbach [50] | R/R after ≥1 line of therapy; regardless of prior txp | 61 | 76 (ipi) 89 (nivo) 82 (triplet) | 1.2 yr (ipi) | G3–4 rash (9–26%) Grade 5 dyspnea (5%) * triplet G4 Stevens Johnson syndrome (5%) * triplet | ||
Nivolumab → ICE | Herrera [51] | R/R after 1 line therapy (pre ASCT) | 39 | 89 | 86 | 1Y: 79 | 1Y: 97 | Grade 3 thrombocytopenia (3%) * Nivo alone Grade 4 altered mental status (3%) * Nivo alone Grade 3–4 neutropenia (3%) * NICE |
Pembrolizumab + GVD | Moskowitz [52,53] | R/R after 1 line therapy (pre ASCT) | 38 | 100 | 95 | G3 elevated LFTs (10%) G3 Neutropenia (10%) G3 mucositis (5%) | ||
Pembro vs. BV (KEYNOTE 204) | Kuruvilla [54] | R/R (post ASCT) or txp ineligible | 304 | 66% (pembro) vs. 54% (BV) | 13.2 mo (pembro) vs. 8.3 mo (BV) | G3–5 pneumonitis (1–4%) G3–5 neutropenia (2–7%) |
4. BV Combinations
5. Immunotherapy
6. BV and Immunotherapy Combinations
7. Immunotherapy and Chemotherapy Combinations
8. Transplant Ineligible
9. Post-Transplant Maintenance/Consolidation
10. Salvage Radiation
11. Discussion
12. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Regimen | Trial | # Pts | ORR (%) | CR (%) | |
---|---|---|---|---|---|
ESHAP | Etoposide, cytarabine, cisplatin, methylprednisolone | Aparicio [10] | 22 | 73 | 41 |
ASHAP | Adriamycin, solumedrol, high-dose cytarabine, cisplatin | Rodriguez [11] | 56 | 70 | 34 |
DHAP | Dexamethasone, cytarabine, cisplatin | Josting [12] | 281 | NR | 72 |
ICE | Ifosfamide, carboplatin, etoposide | Moskowitz [13] | 65 | 88 | 26 |
ICE | Ifosfamide, carboplatin, etoposide | Hertzberg [14] | 6 | 100 | 67 |
IVOx | Ifosfamide, etoposide, oxaliplatin | Sibon [15] | 34 | 76 | 32 |
GDP | Gemcitabine, dexamethasone, cisplatin | Baetz [16] | 23 | 69 | 17 |
GEM-P | Gemcitabine, cisplatin, methylprednisolone | Chau [17] | 21 | 80 | 24 |
IGEV | Ifosfamide, gemcitabine, vinorelbine, prednisone | Santoro [18] | 91 | 81 | 54 |
BeGEV | Bendamustine, gemcitabine, vinorelbine | Santoro [19] | 59 | 75 |
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Takiar, R.; Karimi, Y. Novel Salvage Therapy Options for Initial Treatment of Relapsed/Refractory Classical Hodgkin’s Lymphoma: So Many Options, How to Choose? Cancers 2022, 14, 3526. https://doi.org/10.3390/cancers14143526
Takiar R, Karimi Y. Novel Salvage Therapy Options for Initial Treatment of Relapsed/Refractory Classical Hodgkin’s Lymphoma: So Many Options, How to Choose? Cancers. 2022; 14(14):3526. https://doi.org/10.3390/cancers14143526
Chicago/Turabian StyleTakiar, Radhika, and Yasmin Karimi. 2022. "Novel Salvage Therapy Options for Initial Treatment of Relapsed/Refractory Classical Hodgkin’s Lymphoma: So Many Options, How to Choose?" Cancers 14, no. 14: 3526. https://doi.org/10.3390/cancers14143526