Durvalumab Shows Few High-Grade AEs in Cutaneous T-Cell Lymphoma

Commentary
Video

Safety results from a phase 2 trial show that most toxicities with durvalumab treatment were manageable and low or intermediate in severity.

According to Christiane Querfeld, MD, PhD, few patients had grade 3 toxicities with durvalumab monotherapy treatment or treatment with durvalumab (Imfinzi) plus lenalidomide (Revlimid) for cutaneous T-cell lymphoma.

CancerNetwork® spoke with Christiane Querfeld, MD, PhD, professor and director of the Cutaneous Lymphoma Program at City of Hope, about common toxicities associated with durvalumab with or without lenalidomide in patients with cutaneous T-cell lymphoma, as well as best practices for managing these toxicities. Querfeld presented preliminary findings of a randomized phase 2 trial (NCT03011814) evaluating the combination therapy in this patient population at the 2024 American Society of Hematology Annual Meeting & Exposition (ASH).

Querfeld explained that patients in both durvalumab arms primarily experienced grade 1 or 2 toxicities, including skin toxicities and fatigue, as well as itching, diarrhea, nausea, and vomiting. She expressed that more toxicities were observed in the combination arm, before stating that tumor flare was the most common immune-related event, followed by thyroid dysfunction, including hyperthyroidism and hypothyroidism. Querfeld said that many of these lower grade toxicities were manageable.

Furthermore, Querfeld expressed that grade 3 toxicity incidence was low, pointing to a thromboembolic event and a patient with low neutrophil and white blood cell counts in the combination arm, and constitutional symptoms in the monotherapy arm.

According to safety findings (n = 25) from the trial, the most common treatment-related adverse effects (TRAEs) in the combination arm included fatigue (n = 10), diarrhea (n = 5), and anemia (n = 5). Common grade 3 or higher toxicity in the combination arm included leukopenia (n = 2), neutropenia (n = 2), thromboembolic events (n = 1), and dyspnea (n = 1).

Transcript:

In terms of toxicity, both arms showed mostly grade 1 or 2 toxicities, [which] included mainly skin [toxicities], fatigue, and symptoms like itching, diarrhea, nausea, and vomiting. In general, the toxicities were more commonly seen in the combination arm. In terms of immune-related events, tumor flare was the most common, followed by a quarter of the patients in both arms [having] thyroid dysfunctions. It [included] hyper– or hypothyroidism, and this was easily manageable. Most patients had grade 1 and grade 2 [toxicities].

In terms of grade 3 or higher toxicities, there were few patients, which included, in the combination arm, 1 patient with a thromboembolic event and another patient who had low neutrophil and white blood cell counts in general, while more constitutional symptoms were seen in the single-agent arm. In total, we also analyzed some correlative markers to see if there is any evidence on the microenvironment of the tumor cells.

We have shown that, in the combination arm, you could see an increase in tumor infiltrating CD8-positive T cells and NK cells and a decrease in tumor cells. Iin the single-agent arm, we did not see a significant increase in the tumor cells. Also, the cell-cell communication between tumor cells and immune cells, particularly immune suppressive cells, was largely interrupted in the combination arm, but was not seen [as much] in the single-agent arm. In essence, we are excited about these results because they are higher than we have seen with any standard regimen to date.

Reference

Querfeld C, Chen L, Wu X, et al. Randomized phase 2 trial of the anti-pd-l1 monoclonal antibody durvalumab plus lenalidomide versus single-agent durvalumab in patients with refractory/advanced cutaneous T cell lymphoma. Blood. 2024;144(suppl 1):468. doi:10.1182/blood-2024-205617

Newsletter

Stay up to date on recent advances in the multidisciplinary approach to cancer.

Recent Videos
According to Jorge Nieva, MD, there are a multitude of things that can be explored to enhance the treatment landscape for lung cancer.
Taletrectinib showed improved efficacy in patients with ROS1-positive non–small cell lung cancer who were treatment-naïve.
“It’s a drug that I’m very comfortable with, and it is a drug I’ll likely use primarily in the first-line setting,” stated Jorge Nieva, MD, on taletrectinib in non–small cell lung cancer.
Those being treated for peritoneal carcinomatosis may not have to experience the complication rates or prolonged recovery associated with surgical options.
For patients with peritoneal carcinomatosis, integrating PIPAC into a treatment regimen does not interrupt their systemic therapy.
According to Benjamin J. Golas, MD, PIPAC could be used as a bridging therapy before surgical debulking or between subsequent large surgical operations.
Related Content