Mohammad Jad Moussa: Nivolumab plus ipilimumab in metastatic variant histology renal cell carcinoma

Mohammad Jad Moussa, Oncology Fellow at MD Anderson Cancer Center, shared a post on X about a paper he co-authored with colleagues published in the Journal for ImmunoTherapy of Cancer:

“Efficacy and safety of nivolumab plus ipilimumab in patients with metastatic variant histology (non-clear cell) renal cell carcinoma”

Authors: Mohammad Jad Moussa, Jaanki Khandelwal, Nathaniel Wilson, Omar Alhalabi, Nizar Tannir et al.

“Now in Journal for ImmunoTherapy of Cancer Nivolumab plus ipilimumab in metastatic variant histology renal cell carcinoma.

Mentored by kidney cancer legend Nizar Tannir, Omar Alhalabi, happy to share our experience at MD Anderson Cancer Center co-led with terrific friends Nate Wilson and Jaanki!

Data on nivo/ipi in vhRCC is limited – CheckMate 920 (n=52) by Tykodi SS et al.

Reported an ORR of 19.6%. Responses seen exclusively among patients with papillary and unclassified RCC.

Limited evidence from retrospective series (ORRs 30-36%, 1L nivo/ipi >> salvage).

Study Design

Retrospective review of 55 patients treated in MD Anderson Cancer Center (2017–2024).

• Advanced vhRCC (pRCC, chRCC, uRCC) confirmed by our expert GU pathologists
• Exclusion: VHL-mutated ccRCC (confirmed by NGS)
• Baseline characteristics shown below.

Efficacy

• ORR 36.4% in cohort, with highest ORR in pRCC (48%) and lowest in chRCC (25%)
• Median DoR in cohort: 8.5 months; 20.1 months for 12 patients with pRCC
• Patients with pRCC also the longest OS and PFS, the highest 6-month and 12-month PFS milestones, and the longest TTNT!

Insights on Sarcomatoid Features (SF) (n=20)

• ORR 55% in this subset; 66.7% (4/6) in both pRCC and uRCC; 37.5% (3/8) in chRCC!
• Among patients with uRCC (n=18), median PFS was longer and clinically meaningful in patients with SF vs witho SF
• Limited numbers for inference in other subtypes.

Treatment Itinerary of Our Patients

• About 2/3rds of patients had up to 4 cycles of induction nivo/ipi without maintenance nivo
• 20 (36.4%) patients received maintenance nivo after completion of all 4 induction cycles
• 4 patients underwent cytoreductive nephrectomy, all after maintenance nivo.

Genetic Characterization in Oncoplot

• low TMB poorly correlating with clinical outcomes
• Somatic alt in uRCC: TP53, TERT PTEN; NF2 and SETD2 –> – prognostic factors explaining low mOS and mPFS?
• Distinct molecular profiles of pRCC and chRCC: TERT mut + in pRCC and TP53 mutation + in chRCC.

What do we know now in vhRCC?

• Single-agent ICIs not optimal in 1L treatment of patients with vhRCC, except notable efficacy of pembro in KN427 Cohort B
• chRCC: low RRs with other ICI combos (ORR 0% w/ cabo+nivo; 11.1% with cabo+atezo); response to nivo/ipi only with SF+ in our study

More relevant expert insights on vhRCC, active ICI combinations and the recent SUNNIIFORECAST results, here.

Key Takeaways!

• Nivo/Ipi efficacy as 1L treatment in pRCC
• SF predictor of high responses across 3 subtypes; all responses in chRCC (ORR 25%) and most in uRCC (ORR 27.8%) occurring in tumors with SF
• uRCC: limited PFS and inferior OS – variable efficacy of nivo/ipi in vhRCC subtypes

Special thanks to our patients, co-authors, Katie Coleman for endless support and motivation, legend Dr. Nizar Tannir and mentors Matt Campbell and Omar Alhalabi! Work was recently presented at GU ASCO 2025 (thanks to organizers).

Graphical abstract for the visual learner.”

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