Loncastuximab tesirine can produce durable responses in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), results from the LOTIS-2 trial suggest.
In this phase 2 trial, the median duration of response exceeded 1 year overall and was not reached among patients who achieved a complete response (CR). These results were published in Haematologica.
The LOTIS-2 trial (ClinicalTrials.gov Identifier: NCT03589469) was designed to evaluate loncastuximab tesirine — an anti-CD19 antibody conjugated to a pyrrolobenzodiazepine dimer — in patients with heavily pretreated DLBCL.
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The trial included 145 evaluable patients. Their median age at baseline was 66.0 years, and 58.6% were men. The patients had received a median of 3 prior therapies (range, 2-7), 20.0% had primary refractory disease, 61.4% had disease that was refractory to their last systemic therapy, 9.7% had previously received chimeric antigen receptor T-cell therapy, and 16.6% had received a transplant.
Patients received loncastuximab tesirine every 3 weeks at 0.15 mg/kg for the first 2 cycles and at 0.075 mg/kg thereafter for up to 1 year. The median follow-up was 7.8 months.
The overall response rate was 48.3%, and the CR rate was 24.8%. Of the 36 patients who achieved a CR, 16 (44%) were event-free for at least 1 year, and 11 (31%) were event-free for at least 2 years.
The median duration of response was 13.4 months overall and was not reached in patients who achieved a CR. Most patients who achieved a CR maintained a response for 1 year (82.8%) or 2 years (72.4%).
The median progression-free survival (PFS) was 4.9 months overall and was not reached in patients who achieved a CR. Among complete responders, the estimated PFS rate was 82.9% at 1 year and 72.5% at 2 years.
The median overall survival (OS) was 9.5 months overall and was not reached in patients who achieved a CR. Among complete responders, the estimated OS rate was 77.1% at 1 year and 68.2% at 2 years.
Treatment-emergent adverse events (TEAEs) were seen in 98.6% of patients. The most common TEAEs were increased gamma-glutamyl transferase (42%), neutropenia (40%), and thrombocytopenia (33%).
The rate of grade 3 or higher TEAEs was 73.8%. The most common of these were neutropenia (26%), thrombocytopenia (18%), increased gamma-glutamyl transferase (17%), and anemia (10%).
There were no treatment-related deaths and no cases of secondary malignancy or myelodysplastic syndrome.
“With additional follow-up, [loncastuximab tesirine] continued to demonstrate durable, long-term responses with manageable safety and tolerability in patients with CR,” the researchers concluded.
Disclosures: This research was supported by ADC Therapeutics SA. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Caimi PF, Ai WZ, Alderuccio JP, et al. Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: Long-term efficacy and safety from the phase 2 LOTIS-2 study. Haematologica. Published online August 31, 2023. doi:10.3324/haematol.2023.283459
