Cohort 2 of KEYNOTE-023: Pembrolizumab-Based Combination for Resistant Myeloma
Posted: Friday, September 17, 2021
The use of the PD-1 inhibitor pembrolizumab in combination with other agents to treat resistant multiple myeloma has had a somewhat rocky road. First, the U.S. Food and Drug Administration (FDA) placed a clinical hold on active studies of pembrolizumab in combination with dexamethasone plus lenalidomide (KEYNOTE-185, Cohort 1 of KEYNOTE-023) or pomalidomide (KEYNOTE-183), based on its determination of a higher risk for death among patients receiving these pembrolizumab combinations. Then, a partial clinical hold was placed on Cohort 2 of KEYNOTE-023, which assessed the combination of pembrolizumab, low-dose dexamethasone, and carfilzomib.
In a correspondence published in the British Journal of Haematology, Jesus San Miguel, MD, of the University of Navarra, Pamplona, Spain, and colleagues presented the results from Cohort 2.
“Although the truncated size and duration of Cohort 2 of the KEYNOTE-023 study preclude drawing definitive conclusions, the data suggest that combination therapies with a PD-1 inhibitor may still be a potential therapeutic option for patients with multiple myeloma.”
From October 31, 2016, to September 15, 2017, 10 patients (median age 61, with measurable resistant myeloma and one to three lines of prior therapy) were enrolled in Cohort 2. A median of 9.5 cycles of pembrolizumab, 42.0 cycles of carfilzomib, and 51.0 cycles of dexamethasone was administered. Median follow-up was 26 months after treatment began.
Adverse effects related to treatment were reported in eight patients. They ranged from fatal multiple organ dysfunction syndrome (one patient) to pneumonia (five patients). In addition, neutropenia, thrombocytopenia, hypothyroidism, hypophysitis, and nephritis were also observed.
The tumor objective response rate was 70.0% (95% confidence interval [CI] = 34.8%–93.3%), with a median duration of response of 14.1 months. The median progression-free survival was 14.3 months (95% CI = 2.0–19.6 months), and the median overall survival was 22.5 months (95% CI = 2.0 months to not available).
Disclosure: For full disclosures of the study authors, visit the onlinelibrary.wiley.com.
