Résumé
Introduction
Cutaneous T cell lymphomas (CTCL) are a heterogeneous group of T cell derived extranodal non-Hodgkin lymphomas that, primarily affect the skin and blood. The most frequent subtype of CTCL is mycosis fungoides (MF), accounting for about 60% of all cases, whilst Sézary syndrome (SS) is much rarer and more aggressive.
Patients (pts) with advanced and heavily pretreated relapsed/refractory CTCL have worse health-related quality of life (HRQoL) than those at earlier stages of the disease and have limited treatment options. CTCL pts suffer from debilitating itching and recurrent skin infections which, together with their underlying disease has a profound effect on social wellbeing and a major impact on quality of life.
Lacutamab, a novel KIR3DL2 monoclonal antibody which depletes the KIR3DL2+ tumor cells, has shown deep and durable responses in the TELLOMAK study (NCT03902184) in pts with CTCL after at least 2 prior systemic lines of treatment. Here, we report patient-reported outcomes (PROs) on HRQoL in SS and MF pts treated with lacutamab from the TELLOMAKstudy.
Methods
TELLOMAK is an open-label, multi-cohort Phase 2 single-arm trial designed to evaluate lacutamab in relapsed/refractory (R/R) SS and MF pts after at least 2 prior systemic therapies. Consistent with recent trials in this setting, HRQoL was assessed using PROs based on the validated Skindex-29 questionnaire that inquiries about how often (Never, Rarely, Sometimes, Often, All the time) during the previous 4 weeks the pt experienced the effect described in each item. All responses are transformed to a linear scale varying from 0 (never) up to 100 (effect experienced all the time). The presence and severity of pruritus was assessed using a 10 point visual analogue scale (VAS) ranging from 0 (no itch) to 10 (worst imaginable itch). Here we report HRQoL results, both in terms of summary at all timepoints and change from baseline.
Results
At the time of data cut-off, for the 56 SS pts enrolled in the TELLOMAK trial, median age was 69, 60.7% were males, median prior lines of systemic therapy was 5, 67.9% of pts had confluence of erythema covering ≥ 80% body surface area (T4). Median follow-up was 14.4 months. At baseline, median VAS was 6.2 and median Skindex-29 global score was 52.7. Treatment with lacutamab was associated with an early decrease of itch intensity starting from W5 with a clinically meaningful decrease of ≥2 points in VAS scale from W13 (VAS≤4) for SS pts that was maintained over time. We also observed an early decrease of Skindex-29 global scores starting from W5 (Skindex 38.7) with a continuous and deep decrease over time (i.e. Skindex 27.8 at W13 then 14.4 at W45) for SS pts.
For the 107 MF pts enrolled, median age was 62 years, 67.3% were male, median prior lines of systemic therapy was 4, 15.9% of pts were T4. Median follow-up was 11.8 months. At baseline, median VAS was 6.0 and median Skindex-29 global score was 56.3. We observed an early and slight improvement in itch intensity from W5 (VAS 5) then later deeper decrease with VAS≤4 from W37. We also observed an early slight decrease of Skindex-29 starting from W5 (Skindex 46.3) then later a deeper decrease (i.e. Skindex 38.8 at W29).
Description of subgroups according to clinical response and KIR3DL2 levels expression will be further presented.
Conclusion
Meaningful improvements from baseline in CTCL overall HRQoL and in pruritus intensity were observed in the TELLOMAK trial assessing lacutamab monotherapy, with durable improvements from Week 5. These favorable HRQoL results compliment the established efficacy and safety profile of lacutamab, highlighting its potential as a compelling future treatment option for CTCL patients with unmet need.
Bagot:Recordati: Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees; Innate-Pharma: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Kim:Mundipharma: Membership on an entity's Board of Directors or advisory committees; Innate-Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kyowa Kirin Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Soligenix: Research Funding; Galderma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trillium: Research Funding; Secura Bio: Honoraria, Membership on an entity's Board of Directors or advisory committees; Elorac: Research Funding; Eisai: Research Funding; DrenBio: Research Funding; CRISPR Therapeutics: Research Funding; Pfizer/Seattle Genetics: Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Portola/Alexion Pharma: Research Funding. Dalle:BMS: Other: congress invitation, Research Funding; Pierre Fabre: Research Funding; Astra Zeneca: Research Funding; Sanofi: Current equity holder in publicly-traded company, Other: Spouse of employee; MSD: Other: congress invitation, Research Funding. Mehta-Shah:Dizal Pharmaceuticals: Research Funding; Genetech/Roche: Consultancy, Research Funding; Morphosys: Research Funding; Johnson & Johnson/Janssen: Consultancy; Innate Pharmaceuticals: Research Funding; Verastem Oncology: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Celgene: Research Funding; Yingli Pharmaceuticals: Research Funding; Secura Bio: Consultancy, Research Funding; Pfizer: Consultancy; C4 Therapeutics: Consultancy, Research Funding; Bristol Myers-Squibb: Research Funding; Astra Zeneca: Consultancy, Research Funding; Corvus Pharmaceuticals: Research Funding; Kyowa Hakko Kirin, Karyopharm Therapeutics: Consultancy. Huen:Blueprint Medicines: Consultancy; Kyowa Kirin: Research Funding; CRISPR: Research Funding; Kymera Therapeutics: Research Funding; Innate Pharma: Research Funding; Scitech: Research Funding; Trillium Therapeutics: Research Funding. Poligone:Astex Pharmaceuticals: Research Funding; Bioniz: Research Funding; Helsinn: Research Funding, Speakers Bureau; Innate-Pharma: Research Funding; Kyowa Hakko Kirin: Consultancy, Honoraria, Research Funding, Speakers Bureau; Miragen: Research Funding; Regeneron: Consultancy, Speakers Bureau; Soligenix: Research Funding; Stemline Therapeutics: Consultancy, Speakers Bureau. Zinzani:CELLTRION: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KYOWA KIRIN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC THERAPEUTICS: Membership on an entity's Board of Directors or advisory committees; ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TAKEDA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ASTRAZENECA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANDOZ: Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SECURA BIO: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN-CILAG: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSAPHARMA: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; INCYTE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BEIGENE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Geskin:Mallinckrodt: Research Funding; Kyowa Kirin: Research Funding. Sokol:Kyowa Kirin, Inc: Consultancy, Research Funding; CRISPR Therapeutics: Consultancy; EUSA: Research Funding. Beylot-Barry:Almirall: Consultancy, Research Funding; Kyowa: Consultancy, Research Funding. Khodadoust:Nutcracker Therapeutics: Research Funding; CRISPR Therapeutics: Research Funding. Battistella:Cerba Research: Consultancy; Recordati: Consultancy; Bristol Myers Squibb: Consultancy, Speakers Bureau; Kyowa kirin: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Innate-Pharma: Consultancy. Gru:Innate-Pharma: Consultancy. Viotti:Innate-Pharma: Current Employment, Current equity holder in publicly-traded company. Paiva:Innate Pharma: Current Employment, Current equity holder in publicly-traded company. Boyer Chammard:Innate Pharma: Current Employment, Current equity holder in publicly-traded company. Porcu:Viracta therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; SOBI: Consultancy, Honoraria, Speakers Bureau; ONO: Consultancy, Research Funding; Innate-Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; DAIICHI: Consultancy, Honoraria; Teva: Consultancy, Research Funding; Kiowa Kirin: Honoraria, Research Funding.