Relevance, Risks, and Benefits of Early-Phases Clinical Trials Participations for Patients With Hematological Malignancies From 2008 to 2023

Matteo Guerra; Emily Alouani; Thomas Hueso; Kaissa Ouali; Alina Danu; Antoine Hollebecque; Rastislav Bahleda; Christophe Willekens; Anas Gazzah; Capucine Baldini; Sophie Postel-Vinay; Jean-Baptiste Micol; Christophe Massard; Stéphane De Botton; Vincent Ribrag; Jean-Marie Michot

doi:10.1111/ejh.14307

Relevance, Risks, and Benefits of Early-Phases Clinical Trials Participations for Patients With Hematological Malignancies From 2008 to 2023

Eur J Haematol. 2024 Sep 21. doi: 10.1111/ejh.14307. Online ahead of print.

Authors

Matteo Guerra¹, Emily Alouani¹, Thomas Hueso¹, Kaissa Ouali¹, Alina Danu², Antoine Hollebecque¹, Rastislav Bahleda¹, Christophe Willekens², Anas Gazzah¹, Capucine Baldini¹, Sophie Postel-Vinay^{1

3}, Jean-Baptiste Micol², Christophe Massard^{1

4}, Stéphane De Botton^{2

4

5}, Vincent Ribrag^{1

2

5}, Jean-Marie Michot^{1

2

5}

Affiliations

¹ Département des Innovations Thérapeutiques et des Essais Précoces (DITEP), Gustave Roussy, Villejuif, France.
² Département d'Hématologie, Gustave Roussy, Villejuif, France.
³ INSERM U981, Gustave Roussy, Villejuif, France.
⁴ Université Paris-Saclay, Villejuif, France.
⁵ INSERM U1170, Gustave Roussy, Villejuif, France.

PMID: 39305190
DOI: 10.1111/ejh.14307

Abstract

Background: Early-phases clinical trials (Phases 1 and 2) have evolved from a traditional assessment of toxicity to an adaptive approach based on patients' medical needs and access to effective new therapies. The global risks, benefits, and relevance of early-phases clinical trials participation for patients with hematological malignancies remain poorly evaluated.

Patients and methods: All early-phases clinical trials participations for patients with hematological malignancies, from 2008 to 2023, in a tertiary academic center in Europe, were reviewed. Patient's demographics, tumor type categories, therapeutic responses, mortality, overall survival (OS), and investigational product (IP) were assessed.

Results: Over the period 2008-2023, 736 patients participating in 92 different early-phases clinical trials, were analyzed. The most common tumor categories were diffuse large B-cell lymphoma (n = 253; 34.4%), acute myeloid leukemia/myelodysplastic syndrome (n = 164; 22.3%) and multiple myeloma (n = 100; 13.6%). The median OS was 14.8 (95% CI: 12.4-17.9) months and response rate 31.9%, including complete responses in 13.5% of patients. By tumor categories, the highest and lowest median duration of OS were observed for patients with Hodgkin lymphoma (99.8; [95% CI: 47.0-not reached] months) and peripheral T-cell lymphoma (8.9 [95% CI: 5.3-12.0] months), respectively. The on-protocol and treatment-related mortality rates were 5.43% and 0.54%, respectively. Overall response rate was 29.1% including 13.5% of complete response. Overall, 202 (27.5%) patients received an IP later approved by the health authorities, and those patients had better OS (18.2 months vs. 12.1 months HR: 1.160 [95% CI; 0.6977-1.391], p = 0.0283).

Conclusion: In conclusion, patients with hematologic malignancies who have participated in early-phases clinical trials over the past 15 years have achieved variable therapeutic response rates, acceptable risk/benefit ratio and potentially significant therapeutic advantages. This study provides framework material for hematologists to further discuss clinical trial participation with their patients.

Keywords: Phase 1; benefit risk assessment; clinical protocols; clinical trial; hematological malignancies; survival analysis.