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Immunotherapy Response Prediction - Examples

Example 1: High-Biomarker NSCLC (Expected: HIGH Response)

Input: "NSCLC patient, TMB 25 mut/Mb, PD-L1 TPS 80%, no STK11/EGFR mutations. Predict ICI response."

Expected Score Breakdown:

Component Value Score
TMB 25 (High) 30
MSI Unknown 10
PD-L1 80% (High) 20
Neoantigens Est. moderate 10
Resistance None 0
Sensitivity None 0
TOTAL 70

Expected Recommendation: Pembrolizumab monotherapy (KEYNOTE-024: 44.8% ORR, 10.3mo PFS with PD-L1>=50%)

Example 2: Melanoma with BRAF V600E

Input: "Melanoma, BRAF V600E, TP53 R175H, TMB 15 mut/Mb, PD-L1 50%, MSS"

Expected Score Breakdown:

Component Value Score
TMB 15 (Intermediate) 20
MSI MSS 5
PD-L1 50% 20
Neoantigens Moderate (~10-20) 10
Resistance None ICI-specific 0
Sensitivity None 0
TOTAL 55

Expected Recommendation: MODERATE response. Consider:

  1. ICI first if no rapid progression risk: pembrolizumab or nivolumab
  2. BRAF/MEK targeted (dabrafenib+trametinib) if rapid response needed
  3. Nivolumab + ipilimumab for aggressive approach

Example 3: MSI-High Colorectal Cancer

Input: "Colorectal cancer, MSI-high, TMB 40 mut/Mb"

Expected Score Breakdown:

Component Value Score
TMB 40 (High) 30
MSI MSI-H 25
PD-L1 Unknown 10
Neoantigens High (MSI-H) 15
Resistance None 0
Sensitivity High TMB/MSI-H 5
TOTAL 85

Expected Recommendation: HIGH response. Pembrolizumab first-line (KEYNOTE-177: 43.8% ORR, 16.5mo PFS)

Example 4: Low-Biomarker NSCLC with Resistance

Input: "NSCLC, TMB 2 mut/Mb, PD-L1 <1%, STK11 loss of function mutation"

Expected Score Breakdown:

Component Value Score
TMB 2 (Very Low) 5
MSI Unknown 10
PD-L1 <1% 5
Neoantigens Low 5
Resistance STK11 loss -10
Sensitivity None 0
TOTAL 15

Expected Recommendation: LOW response. ICI monotherapy unlikely effective.

  1. Platinum-based chemotherapy preferred
  2. Consider ICI + chemotherapy combination (may have modest benefit)
  3. Clinical trial enrollment

Example 5: Bladder Cancer Moderate Profile

Input: "Bladder cancer, TMB 12 mut/Mb, PD-L1 CPS 10, no resistance mutations"

Expected Score Breakdown:

Component Value Score
TMB 12 (Intermediate) 20
MSI Unknown 10
PD-L1 10% (Positive) 12
Neoantigens Moderate 10
Resistance None 0
Sensitivity None 0
TOTAL 52

Expected Recommendation: MODERATE response.

  1. Pembrolizumab (second-line, KEYNOTE-045: 21.1% ORR)
  2. Atezolizumab (second-line option)
  3. Avelumab maintenance after platinum

Example 6: RCC (Renal Cell Carcinoma)

Input: "Clear cell RCC, no specific mutations reported, PD-L1 positive"

Expected Score Breakdown:

Component Value Score
TMB Unknown 15 (neutral, RCC context)
MSI Unknown 10
PD-L1 Positive (1-49%) 12
Neoantigens Unknown 8
Resistance None known 0
Sensitivity None 0
TOTAL 45

Expected Recommendation: MODERATE response (RCC is ICI-responsive despite low TMB).

  1. Nivolumab + ipilimumab (CheckMate-214: 42% ORR for intermediate/poor risk)
  2. Pembrolizumab + axitinib (KEYNOTE-426: 59% ORR)
  3. Nivolumab + cabozantinib (CheckMate-9ER)

Note: RCC is a special case where TMB is not as predictive.

Example 7: HNSCC with CPS

Input: "Head and neck squamous cell carcinoma, PD-L1 CPS 25, TMB 8 mut/Mb"

Expected Score:

Component Value Score
TMB 8 (Low) 10
MSI Unknown 10
PD-L1 CPS 25 (High) 20
Neoantigens Low-Moderate 8
Resistance None 0
TOTAL 48

Expected Recommendation: MODERATE response. Pembrolizumab monotherapy (KEYNOTE-048: CPS>=20, 23.3% ORR mono, 36% combo)

Example 8: Edge Case - Conflicting Biomarkers

Input: "NSCLC, TMB 30 mut/Mb (high), PD-L1 <1% (negative), JAK2 mutation"

Expected Score:

Component Value Score
TMB 30 (High) 30
MSI Unknown 10
PD-L1 <1% 5
Neoantigens Moderate-High 12
Resistance JAK2 mutation -10
TOTAL 47

Expected Recommendation: MODERATE but with caveats. High TMB suggests neoantigen load, but JAK2 mutation may impair IFN-gamma signaling. Consider combination ICI or clinical trial.