Nivolumab + Tacrolimus + Prednisone ± Ipilimumab for Kidney Transplant Recipients With Advanced Cutaneous Cancers-Reference-Cited by-同舟云学术

Nivolumab + Tacrolimus + Prednisone ± Ipilimumab for Kidney Transplant Recipients With Advanced Cutaneous Cancers

Published:2024-03-20 Issue:9 Volume:42 Page:1011-1020
ISSN:0732-183X
Container-title:Journal of Clinical Oncology
language:en
Short-container-title:JCO

Author:

Schenk Kara M.¹²^ORCID,Deutsch Julie Stein³⁴,Chandra Sunandana⁵^ORCID,Davar Diwakar⁶^ORCID,Eroglu Zeynep⁷^ORCID,Khushalani Nikhil I.⁷^ORCID,Luke Jason J.⁸^ORCID,Ott Patrick A.⁹,Sosman Jeffrey A.⁵,Aggarwal Vikram¹⁰,Schollenberger Megan D.²,Sharfman William H.²⁴^ORCID,Bibee Kristin P.³^ORCID,Scott Jeffrey F.³¹¹,Loss Manisha J.³^ORCID,Wang Hao⁴¹²,Qi Hanfei¹²^ORCID,Sharon Elad¹³^ORCID,Streicher Howard¹³,Chen Helen X.¹³,Woodward Robert N.¹⁴^ORCID,Bagnasco Serena M.¹⁵,Taube Janis M.³⁴^ORCID,Topalian Suzanne L.⁴¹⁶^ORCID,Brennan Daniel C.¹⁷^ORCID,Lipson Evan J.²⁴^ORCID

Affiliation:

1. Department of Oncology, Bozeman Health Deaconess Cancer Center, Bozeman, MT

2. Department of Oncology, Johns Hopkins University, Baltimore, MD

3. Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD

4. Bloomberg-Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD

5. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL

6. Department of Medicine and UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA

7. Department of Cutaneous Oncology, The Moffitt Cancer Center and Research Institute, Tampa, FL

8. Cancer Immunotherapeutics Center, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA

9. Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA

10. Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL

11. Clinical Skin Center of Northern Virginia, Fairfax, VA

12. Division of Quantitative Sciences, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD

13. National Cancer Institute, Investigational Drug Branch, Cancer Therapy Evaluation Program, Bethesda, MD

14. CareDx, Brisbane, CA

15. Department of Pathology, Johns Hopkins University School of Medicine and Johns Hopkins Hospital, Baltimore, MD

16. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD

17. Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD

Abstract

PURPOSE Cancer-related mortality rates among kidney transplant recipients (KTR) are high, but these patients have largely been excluded from trials of immune checkpoint inhibitors because of immunosuppression and risk of treatment-related allograft loss (TRAL). We conducted a prospective clinical trial testing nivolumab (NIVO) + tacrolimus (TACRO) + prednisone (PRED) ± ipilimumab (IPI) in KTR with advanced cutaneous cancers. METHODS Adult KTR with advanced melanoma or basal, cutaneous squamous, or Merkel cell carcinomas were eligible. Immunosuppression was standardized to TACRO (serum trough 2-5 ng/mL) + PRED 5 mg once daily. Patients then received NIVO 480 mg IV once every 4 weeks. The primary composite end point was partial or complete (tumor) response (CR) or stable disease per RECIST v1.1 without allograft loss at 16W. Patients with progressive disease (PD) could receive IPI 1 mg/kg IV + NIVO 3 mg/kg once every 3 weeks × 4 followed by NIVO. Donor-derived cell-free DNA (dd-cfDNA) levels were measured approximately once every 2 weeks as a potential predictor of allograft rejection. RESULTS Among eight evaluable patients, none met the trial's primary end point. All eight patients experienced PD on NIVO + TACRO + PRED; TRAL occurred in one patient. Six patients then received IPI + NIVO + TACRO + PRED. Best overall responses: two CR (one with TRAL) and four PD (one with TRAL). In total, 7 of 8 pre-NIVO tumor biopsies contained a paucity of infiltrating immune cells. In total, 2 of 5 on-NIVO biopsies demonstrated moderate immune infiltrates; both patients later experienced a CR to IPI + NIVO. In 2 of 3 patients with TRAL, dd-cfDNA elevations occurred 10 and 15 days before increases in serum creatinine. CONCLUSION In most KTR with advanced skin cancer, TACRO + PRED provides insufficient allograft protection and compromises immune-mediated tumor regression after administration of NIVO ± IPI. Elevated dd-cfDNA levels can signal treatment-related allograft rejection earlier than rises in serum creatinine.

Publisher

American Society of Clinical Oncology (ASCO)

Link

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.23.01497

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