Loncastuximab Tesirine Plus Ibrutinib in Relapsed DLBCL Trends Favorably at LOTIS-3 Interim Analysis – NewsTVPK

An interim analysis of the ongoing phase 2 LOTIS-3 trial (NCT03684694), which was presented at the 2021 Annual Meeting of the American Society of Hematology (ASH), revealed promising efficacy and encouraging safety with the combination of ibrutinib (Imbruvica) plus loncastuximab thesis (Zynlonta) in patients with recurrent / resistant (R / R) diffuse large B-cell lymphoma (DLBCL).

These results led the study authors to change the study protocol to administer loncastuximab at each cycle of therapy to see if it together with ibrutinib improves outcomes in the patient population.

This interim analysis of the phase 2 open-label single-arm study identified a complete response rate (CRR) of 34.3% (95% CI, 19.1% –52.2%) among the total DLBCL cohort. Moreover, there was a 57.1% (95% CI, 39.4% -73.7%) overall response rate (ORR) in the total DLBCL cohort with a mean response time (DOR) of 5.49 months, while DOR was not reached in the non-germline center B-cell-like DLBCL (non-GCB DLBCL), and GCB DLBCL cohorts.

“In the overall DLBCL cohort, 57% of patients responded with a 34% complete response and a 22% partial response,” said lead author Carmelo Carlo-Stella, MD, a full professor of hematology at Humanitas University in Italy, discussing the ORR in virtual presentation of the provisional analysis data at ASH. “(Overall response) was 45% in the non-GCB cohort and 77% in the GCB DCBL cohort with 27% complete response in the non-GCB cohort and 46% complete response in the GCB cohort.”

The total DLBCL cohort, regardless of cell of origin, consisted of 35 patients while 22 of the patients had non-GCB DLBCL, and 13 patients had GCB DLBCL. In the overall DLBCL cohort, patients had a mean age of 72 years (range 19–82) and previously received a median of 3 previous therapies (range, 1–6). At the time of analysis, patients received a median of 2 cycles (range, 1–6) of loncastuximab and 4 cycles (range, 1–10) of ibrutinib.

Assessing the overall DLBCL cohort, mean DOR was different for each therapy with loncastuximab at 49 days (range, 1-246) and 97.5 days (range, 13-386) on ibrutinib. While DOR was not yet achieved in the other cohorts, patients in the non-GCB DLBCL cohort had a 3-month DOR during the first quartile of treatment. According to Carlo-Stella, who is also a principal investigator at the Cancer Experimental Therapy Laboratory at Humanitas Research Hospital, 6 patients in the GCB DLBCL cohort experienced a sustained response at the time of analysis, compared with 3 in the non-GCB DLBCL cohort. cohort.

Patients in this analysis were treated with 60 μg / kg of loncastuximab every 3 weeks for 2 cycles plus 560 mg / day of oral ibrutinib for up to 1 year. Patients who experienced a complete response, partial response, or stable disease received an additional dose of loncastuximab on day 1 of cycles 5, 6, 9, and 10. The primary objective of the study was to evaluate the CRR achieved with loncastuximab plus ibrutinib. with a security rating.

The safety findings, according to Carlo-Stella, were consistent with previous studies of the therapy with 94% of patients experiencing treatment-emergent adverse events (ASDs) of any grade. Thrombocytopenia was the most common ASD among all grades with 68.2% (n = 15) of patients in the non-GCB cohort experiencing it, 46.2% (n = 6) in the GCB cohort, and 60% (n = 21) in the cohort. general cohort. Dose reduction, discontinuation, or discontinuation due to ASDs was observed in 57.1% of all patients. Grade 3 or higher TEAEs were seen in 72.7% (16) of patients in the non-GCB cohort, 15.4% (2) in the GCB cohort, and 51.4% (18), in the total DLBCL cohort . The most common grade 3 or higher TEAE was neutropenia with 8 patients experiencing it, while 3 patients contracted COVID-19.

While Carlo-Stella said the low CRR in the non-GCB cohort was surprising, he realized it could be because the sample size was small. However, he said, researchers plan to add ibrutinib to more cycles of treatment and continue the study.

Reference

Carlo-Stella C, Zinzani P, Janakiram M, et al. Planned Interim Analysis of Phase 2 Study of Loncastuximab Tesirine Plus Ibrutinib in Patients with Advanced Diffuse Large B-Cell Lymphoma (LOTIS-3). Presented at: 63rd Annual Meeting and Exhibition Annual American Society of Hematology; December 11-14, 2021. Summary 54. Accessed December 11, 2021. bit.ly/3GGCalP

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