Risks and benefits of phase 1 clinical trials for patients with relapsed or refractory lymphoma, from 2008 to 2023

Introduction: Previous reviews of phase 1 trials in oncology have reported a treatment response rate 4%–6% and toxicity-related mortality 0.5%. These results may not reflect current Phase trial rates for patients with lymphoma. Methods: All non-pediatric relapsed or refractory (R/R) lymphoma approved by the Cancer Therapy Evaluation Program Institut Gustave Roussy between 2008 2023 (cut-off date 05 January 2023) were reviewed. We on overall survival (OS), rates, treatment-related deaths, number who benefit to received drug clinical which was further health authorities (FDA EMA). Results: analyzed 50 involving 447 participants (pts) R/R at least one dose treatment. assessed toxicity 382/447 (85%) response. The median (range) age 64.9 (19.2–88.5) years. treatments before entering 3 (1–13). main types DLBCL (n = 253; 56.6%), PTCL 45; 10.1%), Hodgkin 40; 8.9%) FL 39; 8.7%). (i.e complete partial responses) 23.6%. Drug classes included epigenetic modifiers 99 pts; 22.1%), Proteolysis Targeting Chimeras (PROTAC) 90; 20.1%), IO 77; 17.2%), anti-apoptotic inhibitor 50; 11.2%), molecular targeted therapy 46; 10.3%), T-Cell Engagers 23; 5.1%), antibody conjugated 20; 4.5%), monoclonal 17; 3.8%), cycle cellular 8; 1.8%), gamma secretase chemotherapy 5; 1.1%), antiangiogenic 4; 0.9%). Trials including involved 84/447 (18.8%) had an 32.9% (26/79 evaluable pts). deaths due toxic events 0.45% (2/447 OS 14.1 (CI95% 11.7–17.9) months, significant variation among (p < 0.0001) (Figure 1). Poor observed peripheral T-cell (8.9 months CI95% 6.9–9.6) Overall from 2023, according type (CLL Chronic lymphoid leukemia; Diffuse large B cell lymphoma; Follicular MCL Mantle MZL Marginal zone WD Waldenstrom disease; Peripheral T lymphoma). Conclusion: are higher than those oncology. Toxicity-related similar research funded by: Ideogen (funding data analysis) Keywords: Aggressive B-cell non-Hodgkin lymphoma, Indolent Conflicts interests pertinent abstract. J. M. Michot Honoraria: (clinical