A Pilot Study of the CD38 Antagonist Daratumumab in Patients with Metastatic Renal Cell Carcinoma or Muscle-Invasive Bladder Cancer.

Autor:	Campbell MT; Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas., Shah AY; Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas., Msaouel P; Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas., Tannir NM; Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas., Siefker-Radtke AO; Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas., Kamat AM; Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas., Navai N; Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas., Dinney CPN; Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas., Rao P; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas., Guo CC; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas., Sheth RA; Department of Interventional Radiology, University of Texas MD Anderson Cancer Center, Houston, Texas., Venkatesan AM; Division of Diagnostic Imaging, Department of Abdominal Imaging, University of Texas MD Anderson Cancer Center, Houston, Texas., Tidwell RS; Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas., Yadav SS; Immunotherapy Platform, University of MD Anderson Cancer Center, Houston, Texas., Gu A; Immunotherapy Platform, University of MD Anderson Cancer Center, Houston, Texas., Chen H; Immunotherapy Platform, University of MD Anderson Cancer Center, Houston, Texas.; James P. Allison Institute, University of MD Anderson Cancer Center, Houston, Texas., Macaluso M; Immunotherapy Platform, University of MD Anderson Cancer Center, Houston, Texas.; James P. Allison Institute, University of MD Anderson Cancer Center, Houston, Texas., Duan F; Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas., Basu S; Immunotherapy Platform, University of MD Anderson Cancer Center, Houston, Texas.; James P. Allison Institute, University of MD Anderson Cancer Center, Houston, Texas., Jindal S; Immunotherapy Platform, University of MD Anderson Cancer Center, Houston, Texas.; James P. Allison Institute, University of MD Anderson Cancer Center, Houston, Texas., Sharma P; Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.; Immunotherapy Platform, University of MD Anderson Cancer Center, Houston, Texas.; James P. Allison Institute, University of MD Anderson Cancer Center, Houston, Texas.; Department of Immunology, University of MD Anderson Cancer Center, Houston, Texas.
Jazyk:	angličtina
Zdroj:	Cancer research communications [Cancer Res Commun] 2024 Sep 01; Vol. 4 (9), pp. 2444-2453.
DOI:	10.1158/2767-9764.CRC-24-0237
Abstrakt:	Purpose: We performed a pilot study of daratumumab (an mAb directed against CD38) in muscle-invasive bladder cancer (MIBC) and treatment-refractory metastatic renal cell carcinoma (mRCC). Experimental Design: Patients with MIBC underwent baseline transurethral resection of the bladder tumor followed by four weekly doses of daratumumab prior to cystectomy. Patients with mRCC underwent baseline and sequential biopsies after eight weekly doses. The primary endpoint was safety. The secondary endpoints were pathologic complete response rate for the MIBC cohort and objective response rate and progression-free survival for the mRCC cohort. Exploratory analyses included immune monitoring and overall survival. A Bayesian sequential monitoring design for toxicity was used for excessive toxicity. Results: In both the MIBC (n = 8) and mRCC (n = 8) cohorts, no toxicity events were encountered. In the MIBC cohort, one patient experienced pathologic complete response rate. In the mRCC cohort, no objective responses were reported, and the median progression-free survival was 1.5 months (95% confidence interval, 1.1-1.8 months). Immune monitoring found significant reductions in NK cells in circulation in both cohorts after treatment. In the tissue analysis, IHC found evidence of diminished CD38 presence in mRCC with treatment, whereas the baseline levels in MIBC were low. Conclusion: Treatment with daratumumab was safe. No signal of efficacy was detected in mRCC, and conclusions on the activity in MIBC were limited. Evidence of daratumumab targeting CD38 was detected in circulating immune cells and within the tumor microenvironment of mRCC and MIBC. Significance: In this prospective clinical trial of daratumumab, treatment in patients with MIBC and mRCC was safe. Limited efficacy was observed. Treatment with daratumumab resulted in CD38-expressing immune cell subsets to be targeted both in circulation and within the tumor microenvironment. (©2024 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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