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. 2022 May 4;14(9):2293.
doi: 10.3390/cancers14092293.

Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study

Umberto Basso  1 , Federico Paolieri  2 , Mimma Rizzo  3 , Ugo De Giorgi  4 , Sergio Bracarda  5 , Lorenzo Antonuzzo  6   7 , Francesco Atzori  8 , Giacomo Cartenì  9 , Giuseppe Procopio  10 , Lucia Fratino  11 , Manolo D'Arcangelo  12 , Giuseppe Fornarini  13 , Paolo Zucali  14   15 , Antonio Cusmai  16 , Matteo Santoni  17 , Stefania Pipitone  18 , Claudia Carella  19 , Stefano Panni  20 , Filippo Maria Deppieri  1 , Vittorina Zagonel  1 , Giampaolo Tortora  21   22
Affiliations

Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study

Umberto Basso et al. Cancers (Basel). .

Abstract

This is a retrospective analysis on the safety and activity of compassionate Ipilimumab and Nivolumab (IPI-NIVO) administered to patients with metastatic Renal Cell Carcinoma (mRCC) with intermediate or poor International Metastatic RCC Database Consortium (IMDC) score as a first-line regimen. IPI was infused at 1 mg/kg in combination with Nivolumab 3 mg/kg every three weeks for four doses, followed by maintenance Nivolumab (240 or 480 mg flat dose every two or four weeks, respectively) until disease progression or unacceptable toxicity. A total of 324 patients started IPI-NIVO at 86 Italian centers. Median age was 62 years, 68.2% IMDC intermediate risk. Primary tumor had been removed in 65.1% of patients. Two hundred and twenty patients (67.9%) completed the four IPI-NIVO doses. Investigator-assessed overall response rate was 37.6% (2.8% complete). Twelve-month survival rate was 66.8%, median progression-free survival was 8.3 months. Grade 3 or 4 treatment-related adverse events occurred in 67 patients (26.9%). IMDC intermediate risk, nephrectomy, BMI ≥ 25 kg/m2, and steroid use for toxicities correlated with improved survival, while age < 70 years did not. IPI-NIVO combination is a feasible and effective regimen for the first-line treatment of intermediate-poor IMDC risk mRCC patients in routine clinical practice.

Keywords: immune-related adverse events; ipilimumab; metastatic Renal Cell Carcinoma; nivolumab; progression; retrospective; survival; toxicity.

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Conflict of interest statement

UB: advisory board for Bristol-Myers Squibb, Speaker’s fees and travel grants from Bristol-Myers Squibb, Ipsen; FP: none; MR: none; UDG: received honoraria for advisory boards or invited speaker fees from Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Novartis, Roche, Clovis, AstraZeneca, institutional research grants from AstraZeneca, Sanofi and Roche; SB: advisory board or steering committee member for Astellas, Janssen, Pfizer, MSD, BMS, IPSEN, Roche, AAA, Bayer, Sanofi-Genzyme, Merck, AstraZeneca, LA: none, FA: none; GC: none; GP: none; LF: none, MDA: none, GF: none; PZ: reports outside the submitted work personal fees for advisory role, speaker engagements, and travel and accommodation expenses from MSD, Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, AstraZeneca, Roche, and Bayer; AC: none, MS: none, SP: none, CC: none; SP: none; FMD: none; VZ: advisory role for Bristol-Myers Squibb, MSD, EISAI and Italfarmaco, speakers’ bureau for Roche, Bristol-Myers Squibb, Astellas, Servier, Astra Zeneca, MSD, Janssen, Ipsen, research funding from Bayer, Roche, Lilly, Astra Zeneca, BMS, Ipsen, Astellas, travel grants from Bayer, Roche, Servier; GT: none.

Figures

Figure 1
Figure 1
OS in 324 patients (median not reached, 12-month OS = 66.8%; 18-month OS = 57.3%, 207 censored, 63.9%).
Figure 2
Figure 2
OS stratified by IMDC score (12-month OS 43.2% in poor vs. 77.2% in intermediate IMDC patients, p = 0.001).
Figure 3
Figure 3
OS stratified by age (12-month OS 66.4% in patients ≥ 70 years vs. 66.9% in younger patients, p = 0.78).
Figure 4
Figure 4
OS stratified by nephrectomy (12-month OS 74.2% in patients undergoing nephrectomy vs. 51.2% in patients who were not, p ≤ 0.0001).
Figure 5
Figure 5
OS stratified by BMI (12-month OS 72.3% in patients with BMI ≥ 25 kg/m2 vs. 62.3% in patients with lower BMI, p = 0.03).
Figure 6
Figure 6
OS stratified by steroid use (12-month OS of 74.6% in patients receiving steroids vs. 62.5% in those who were not, p = 0.017).
Figure 7
Figure 7
PFS in 324 patients (median PFS 8.3 months (95% CI: 6.5–10.1 months, 122 censored, 37.7%).
Figure 8
Figure 8
PFS in intermediate and poor IMDC patients (median PFS 10.4 vs. 2.9 months, p < 0.0001).
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