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

Eur J Haematol. 2025 Jan;114(1):89-97. doi: 10.1111/ejh.14307. Epub 2024 Sep 21.

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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Clinical Trials as Topic*
  • Female
  • Hematologic Neoplasms* / drug therapy
  • Hematologic Neoplasms* / mortality
  • Hematologic Neoplasms* / therapy
  • Humans
  • Male
  • Middle Aged
  • Risk Assessment
  • Treatment Outcome
  • Young Adult