Efficacy outcomes of phase 1 trials in hematologic malignancies have improved in recent years, but rates of fatal toxicities have remained stable, according to a study published in the Journal of Clinical Oncology.

“This study provides broad experience that physicians can use when discussing the potential outcomes for patients with hematologic malignancy considering participating in phase 1 trials,” the researchers wrote.

They evaluated data from 3308 patients enrolled in 161 phase 1 trials of 106 different agents between 2000 and 2019. Most trials (78%) included only patients with hematologic malignancies, but 22% included patients with solid tumors as well.

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Multiple types of agents were assessed in the trials, including cytotoxic chemotherapy, targeted therapies, and immunotherapies, as single agents or in combination.

Fatal Toxicity Over Time

The rate of grade 5 treatment-related toxicities was 1.81% overall and was similar regardless of study activation year.

The risk of grade 5 toxicity was significantly associated with baseline age (odds ratio [OR], 1.02; 95% CI, 1.01-1.04; P =.007 for each 1-year increase), performance status of 2 or higher (OR, 2.76; 95% CI, 1.42-5.37; P =.006), and participation in a disease-specific trial (OR, 1.87; 95% CI, 1.01-3.47; P =.046).

Lymphoma was associated with a lower risk of grade 5 toxicity when acute myeloid leukemia was used as the reference (OR, 0.31; 95% CI, 0.11-0.87).

Efficacy Over Time

Unlike toxicity, efficacy outcomes improved over time. The objective response rate (ORR) increased from 18.5% in trials activated between 2000 and 2005 to 50.6% in trials activated between 2013 and 2019 (P <.001).

The ORR varied across disease types, with the lowest ORR seen in trials of myelodysplastic syndromes (MDS; 0%) and the highest rate in trials of chronic lymphocytic leukemia (78%), acute lymphoblastic leukemia (ALL; 75%), and myeloma (75%).

Complete response (CR) rates also significantly improved over time, from 10.5% in trials activated between 2000 and 2005 to 26.0% in trials activated between 2013 and 2019 (P =.001).

For trials activated between 2013 and 2019, trials of MDS demonstrated the lowest CR rate (0%), and trials of ALL demonstrated the highest CR rate (62.5%).

“These results suggest that physicians and patients should be encouraged to consider phase 1 studies, as meaningful therapeutic outcome can be clearly observed in hematologic malignancies,” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Chihara D, Huang EP, Finnigan SR, et al. Trends in grade 5 toxicity and response in phase I trials in hematologic malignancy: 20-year experience from the cancer therapy evaluation program at the National Cancer Institute. J Clin Oncol. Published online March 9, 2022. doi:10.1200/JCO.21.02190