The 9p24.1 chromosomal alteration in classical Hodgkin lymphoma (cHL) is associated with increased expression of programmed death ligand 1 (PD-L1)/PD-L2 and an immunosuppressive tumor microenvironment. Blockade of PD-L1/PD-1 interactions with avelumab (anti–PD-L1) is hypothesized to restore antitumor immunity. JAVELIN Hodgkins was a phase 1b, multiple-dose, open-label, randomized, parallel-arm trial of avelumab in patients with relapsed/refractory (R/R) cHL. Primary end points included avelumab target occupancy by dose/schedule in peripheral blood immune cells and pharmacokinetic parameters. Secondary end points included safety and antitumor activity. Four dose levels and 2 dosing schedules were investigated: 70, 350, and 500 mg administered every 2 weeks; 500 mg every 3 weeks; and 10 mg/kg every 2 weeks. Thirty-one patients with R/R cHL were randomized; 9 (29.0%) and 20 (64.5%) had received 3 or $4 prior anticancer treatments, respectively. Target occupancy of .90% was observed across all treatment arms, throughout the dosing interval. Avelumab pharmacokinetic data were similar to those previously reported. The most common treatment-related adverse events of any grade were infusion-related reaction (30.0%), nausea (20.0%), increased alanine aminotransferase and rash (16.7% each), and fatigue (13.3%). The objective response rate (ORR) in all randomized patients was 41.9%, with a complete response rate of 19.4%; ORR in those with prior allogeneic hematopoietic stem cell transplant (allo-HSCT) was 55.6%. Due to decreased use of allo-HSCT in patients with R/R cHL, the expansion phase enrolling post–allo-HSCT patients was terminated. Avelumab was tolerable and demonstrated antitumor activity in heavily pretreated patients with cHL, suggesting that PD-L1 blockade may be sufficient for therapeutic benefit in cHL. This trial was registered at www.clinicaltrials. gov as #NCT02603419.

Avelumab in relapsed/refractory classical hodgkin lymphoma: Phase 1b results from the JAVELIN hodgkins trial / Herrera A.F.; Burton C.; Radford J.; Miall F.; Townsend W.; Santoro A.; Zinzani P.L.; Lewis D.; Fowst C.; Brar S.; Huang B.; Thall A.; Collins G.P.. - In: BLOOD ADVANCES. - ISSN 2473-9529. - STAMPA. - 5:17(2021), pp. 3387-3396. [10.1182/BLOODADVANCES.2021004511]

Avelumab in relapsed/refractory classical hodgkin lymphoma: Phase 1b results from the JAVELIN hodgkins trial

Zinzani P. L.;
2021

Abstract

The 9p24.1 chromosomal alteration in classical Hodgkin lymphoma (cHL) is associated with increased expression of programmed death ligand 1 (PD-L1)/PD-L2 and an immunosuppressive tumor microenvironment. Blockade of PD-L1/PD-1 interactions with avelumab (anti–PD-L1) is hypothesized to restore antitumor immunity. JAVELIN Hodgkins was a phase 1b, multiple-dose, open-label, randomized, parallel-arm trial of avelumab in patients with relapsed/refractory (R/R) cHL. Primary end points included avelumab target occupancy by dose/schedule in peripheral blood immune cells and pharmacokinetic parameters. Secondary end points included safety and antitumor activity. Four dose levels and 2 dosing schedules were investigated: 70, 350, and 500 mg administered every 2 weeks; 500 mg every 3 weeks; and 10 mg/kg every 2 weeks. Thirty-one patients with R/R cHL were randomized; 9 (29.0%) and 20 (64.5%) had received 3 or $4 prior anticancer treatments, respectively. Target occupancy of .90% was observed across all treatment arms, throughout the dosing interval. Avelumab pharmacokinetic data were similar to those previously reported. The most common treatment-related adverse events of any grade were infusion-related reaction (30.0%), nausea (20.0%), increased alanine aminotransferase and rash (16.7% each), and fatigue (13.3%). The objective response rate (ORR) in all randomized patients was 41.9%, with a complete response rate of 19.4%; ORR in those with prior allogeneic hematopoietic stem cell transplant (allo-HSCT) was 55.6%. Due to decreased use of allo-HSCT in patients with R/R cHL, the expansion phase enrolling post–allo-HSCT patients was terminated. Avelumab was tolerable and demonstrated antitumor activity in heavily pretreated patients with cHL, suggesting that PD-L1 blockade may be sufficient for therapeutic benefit in cHL. This trial was registered at www.clinicaltrials. gov as #NCT02603419.
2021
Avelumab in relapsed/refractory classical hodgkin lymphoma: Phase 1b results from the JAVELIN hodgkins trial / Herrera A.F.; Burton C.; Radford J.; Miall F.; Townsend W.; Santoro A.; Zinzani P.L.; Lewis D.; Fowst C.; Brar S.; Huang B.; Thall A.; Collins G.P.. - In: BLOOD ADVANCES. - ISSN 2473-9529. - STAMPA. - 5:17(2021), pp. 3387-3396. [10.1182/BLOODADVANCES.2021004511]
Herrera A.F.; Burton C.; Radford J.; Miall F.; Townsend W.; Santoro A.; Zinzani P.L.; Lewis D.; Fowst C.; Brar S.; Huang B.; Thall A.; Collins G.P.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/866835
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