Nivolumab + Tacrolimus + Prednisone ± Ipilimumab for Kidney Transplant Recipients With Advanced Cutaneous Cancers
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
|---|---|
| Enthalten in: |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology - 42(2024), 9 vom: 20. März, Seite 1011-1020 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Schenk, Kara M [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
31YO63LBSN |
|---|
| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 18.03.2024 published: Print-Electronic ClinicalTrials.gov: NCT03816332 Citation Status MEDLINE |
|---|
| doi: |
10.1200/JCO.23.01497 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367434032 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367434032 | ||
| 003 | DE-627 | ||
| 005 | 20240318234117.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240123s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1200/JCO.23.01497 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1334.xml |
| 035 | |a (DE-627)NLM367434032 | ||
| 035 | |a (NLM)38252910 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Schenk, Kara M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Nivolumab + Tacrolimus + Prednisone ± Ipilimumab for Kidney Transplant Recipients With Advanced Cutaneous Cancers |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 18.03.2024 | ||
| 500 | |a Date Revised 18.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03816332 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Nivolumab |2 NLM | |
| 650 | 7 | |a 31YO63LBSN |2 NLM | |
| 650 | 7 | |a Ipilimumab |2 NLM | |
| 650 | 7 | |a Tacrolimus |2 NLM | |
| 650 | 7 | |a WM0HAQ4WNM |2 NLM | |
| 650 | 7 | |a Prednisone |2 NLM | |
| 650 | 7 | |a VB0R961HZT |2 NLM | |
| 650 | 7 | |a Creatinine |2 NLM | |
| 650 | 7 | |a AYI8EX34EU |2 NLM | |
| 650 | 7 | |a Cell-Free Nucleic Acids |2 NLM | |
| 700 | 1 | |a Deutsch, Julie Stein |e verfasserin |4 aut | |
| 700 | 1 | |a Chandra, Sunandana |e verfasserin |4 aut | |
| 700 | 1 | |a Davar, Diwakar |e verfasserin |4 aut | |
| 700 | 1 | |a Eroglu, Zeynep |e verfasserin |4 aut | |
| 700 | 1 | |a Khushalani, Nikhil I |e verfasserin |4 aut | |
| 700 | 1 | |a Luke, Jason J |e verfasserin |4 aut | |
| 700 | 1 | |a Ott, Patrick A |e verfasserin |4 aut | |
| 700 | 1 | |a Sosman, Jeffrey A |e verfasserin |4 aut | |
| 700 | 1 | |a Aggarwal, Vikram |e verfasserin |4 aut | |
| 700 | 1 | |a Schollenberger, Megan D |e verfasserin |4 aut | |
| 700 | 1 | |a Sharfman, William H |e verfasserin |4 aut | |
| 700 | 1 | |a Bibee, Kristin P |e verfasserin |4 aut | |
| 700 | 1 | |a Scott, Jeffrey F |e verfasserin |4 aut | |
| 700 | 1 | |a Loss, Manisha J |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Hanfei |e verfasserin |4 aut | |
| 700 | 1 | |a Sharon, Elad |e verfasserin |4 aut | |
| 700 | 1 | |a Streicher, Howard |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Helen X |e verfasserin |4 aut | |
| 700 | 1 | |a Woodward, Robert N |e verfasserin |4 aut | |
| 700 | 1 | |a Bagnasco, Serena M |e verfasserin |4 aut | |
| 700 | 1 | |a Taube, Janis M |e verfasserin |4 aut | |
| 700 | 1 | |a Topalian, Suzanne L |e verfasserin |4 aut | |
| 700 | 1 | |a Brennan, Daniel C |e verfasserin |4 aut | |
| 700 | 1 | |a Lipson, Evan J |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of clinical oncology : official journal of the American Society of Clinical Oncology |d 1986 |g 42(2024), 9 vom: 20. März, Seite 1011-1020 |w (DE-627)NLM012608777 |x 1527-7755 |7 nnns |
| 773 | 1 | 8 | |g volume:42 |g year:2024 |g number:9 |g day:20 |g month:03 |g pages:1011-1020 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1200/JCO.23.01497 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 42 |j 2024 |e 9 |b 20 |c 03 |h 1011-1020 | ||