Lacutamab in patients with advanced mycosis fungoides (mf): efficacy results according to updated lymph node (ln) classification in the tellomak study

Introduction: Cutaneous T-cell lymphoma (CTCL) is a rare form of non-Hodgkin lymphoma. The most common type is Mycosis Fungoides (MF) accounting for 50%–60% of cases with 25% of patients (pts) having advanced disease (median survival of 1–4 years). KIR3DL2 is a killer immunoglobulin-like receptor, expressed in 50% of MF. Lacutamab is a humanized first-in-class monoclonal antibody targeting KIR3DL2-expressing cells. Global response evaluation is based on 4 compartments: skin, blood, lymph nodes (LN) and viscera (Olsen 2011). LN assessment is an important component of staging and response assessment. The radiologic criteria have recognized limitations in CTCL given their adaptation from guidelines for primary nodal lymphomas. However, recent cooperative group collaboration resulted in a clarification of the guidelines. In MF and SS the pathological assessment of nodal lymphoma should fulfil the criteria for N3 designation (Olsen, 2022), highlighting the importance of utilizing relevant and updated guidelines for accurate assessment of activity. Methods: TELLOMAK is an open-label, phase II trial with multiple cohorts (NCT03902184). Eligible pts received at least 2 prior systemic therapies. MF pts are allocated to one of two cohorts: KIR3DL2 ≥1% MF (Cohort 2) and KIR3DL2 <1% MF (Cohort 3). Lacutamab is administered until progression or unacceptable toxicity. Primary endpoint is Objective Response Rate (ORR). Secondary endpoints include additional efficacy endpoints, safety and quality of life. The MF cohorts follow a Simon 2-stage design. Stage 1 results were presented at EORTC-CL 2022. Per protocol, Stage N0 LNs were not considered as clinically abnormal and Stage N1, N2, N3 or Nx were considered as clinically abnormal at baseline. Here, we present activity data for the same population with the same data cut-off (DCO), but according to these updated recommendations where the criteria for N3 designation are fulfilled. Results: At the DCO of March 04 2022, stage 1 recruitment to cohort 2 and 3 was complete, with 39 pts enrolled, median follow-up was 12.2 months (range: 1–25), median number of previous therapies was 4 (range: 2–15). In cohort 2, among the 21 pts, there were 10 (47.6%) N0, 2 (9.5%) N1, 2 (9.5%) N2, and 7 (33.3%) Nx pts. Global ORR was 28.6% [13.8; 50.0] according to the original classification. According to the updated classification, Global ORR is 42.9% (95% CI [24.5; 63.5]. In cohort 3, among the 18 pts, there were 9 (50%) N0, 3 (16.7%) N1, 1 (5.5%) N2, and 5 (27.8%) Nx pts. Global ORR is 11.1% [3.1; 32.8] according to both classifications. Conclusion: Within the heavily pre-treated MF population enrolled in TELLOMAK, Lacutamab shows clinical activity in KIR3DL2 expressing MF pts, with higher global ORR according to updated LN evaluation. The future adoption of the revised guidelines is welcomed by the CTCL community. Reference: Olsen et al. Blood 2022, 140 (5):419–437. The research was funded by: Innate Pharma Keywords: cutaneous non-Hodgkin lymphoma, molecular targeted therapies Conflicts of interests pertinent to the abstract J. Viotti Employment or leadership position: Employment C. Paiva Employment or leadership position: Employment A. Boyer-Chammard Employment or leadership position: Employment