Among patients with extranodal natural killer/T cell lymphoma (ENKTCL), mitoxantrone hydrochloride liposome (PLM60) plus pegaspargase appears to have promising efficacy, particularly among patients with treatment-naïve disease, according to research presented at ESMO Congress 2022.
Patients with ENKTCL have limited treatment options and represent a population requiring currently unmet clinical needs. PLM60 plus pegaspargase has shown promise in preclinical study in this setting; for this phase 1/2 trial, researchers evaluated the safety and efficacy of this therapeutic combination among patients with ENKTCL.
All included patients had treatment-naïve or relapsed/refractory ENKTCL. Phase 1 had a 3+3 dose-escalation design; phase 2 was a dose expansion experiment using the recommended phase 2 dose as determined in phase 1. All patients included in phase 2 had treatment-naïve disease; the overall study’s primary endpoints were safety and pharmacokinetics.
Data cutoff was in February 2022; at this point, 21 patients had enrolled to phase 1 (12 treatment-naïve; 9 with relapsed/refractory disease) and 10 patients had enrolled to phase 2. Phase 1 showed 2 dose-limiting toxicities: grade 4 neutropenia and grade 3 abdominal pain with PLM60 24 mg/m2. The recommended phase 2 dose was PLM60 24 mg/m2 plus pegaspargase 2000 IU/m2.
Treatment-related adverse events occurred in 100% of patients in phases 1 and 2, 87.1% of which were at least grade 3. The most common grade 3 or worse events included neutropenia (77.4%), leucopenia (74.2%), anemia (54.8%), thrombocytopenia (45.2%), hypertriglyceridemia (22.6%), infectious pneumonia (16.1%), lymphocytopenia (16.1%), decreased fibrinogen level (16.1%), hypoglycemia (12.9%) and elevated bilirubin levels (12.9%).
Efficacy analysis suggested that the complete and overall response rates were 61.3% (95% CI, 42.2-78.2) and 87.1% (95% CI, 70.2-96.4), respectively, with median progression-free survival not reached.
Among 22 patients with treatment-naïve disease, the complete and overall response rates were 68.2% (95% CI, 45.1-86.1) and 90.9% (95% CI, 70.8-98.9), respectively. “PLM60 plus pegaspargase had an encouraging efficacy especially in treatment-naïve ENKTCL pts with manageable safety profiles,” the authors wrote in the abstract.
Huang Y, Wu T, Hu Y, et al. Combination of mitoxantrone hydrochloride liposome with pegaspargase in patients with extranodal NK/T-cell lymphoma: A phase I/II clinical trial. Presented at ESMO 2022; September 9-13, 2022. Abstract 625MO.