What is the treatment regimen for Talimogene (Imlygic) in patients with unresectable stage III or stage IV melanoma?

Talimogene Laherparepvec (T-VEC) Treatment Regimen for Unresectable Stage III or IV Melanoma

Talimogene laherparepvec (T-VEC/Imlygic) is recommended as an intralesional therapy option specifically for patients with unresectable stage IIIB-IVM1a melanoma with injectable cutaneous, subcutaneous, or nodal lesions who are not eligible for or do not desire first-line systemic therapies.

Patient Selection Criteria

• Indicated for patients with:

  • Unresectable stage IIIB, IIIC, or IV-M1a melanoma 1
  • Injectable cutaneous, subcutaneous, or nodal lesions 2
  • No bone, brain, lung, or other visceral disease 1, 2

• T-VEC is most effective in:

  • Earlier stage disease (IIIB/IIIC) with 33% durable response rate 1, 3
  • Stage IV-M1a disease with 16% durable response rate 1
  • Treatment-naïve patients (23.9% durable response rate vs 9.6% in previously treated) 1

Administration Protocol

Dosing Schedule:

1. Initial dose: 10^6 PFU/mL (1 million PFU/mL) on Day 1 2
2. Subsequent doses: 10^8 PFU/mL (100 million PFU/mL) on Day 21 and every 2 weeks thereafter 2
3. Volume: Up to 4 mL per treatment visit 2

Treatment Duration:

• Minimum treatment period: 6 months 2
• Continue treatment until:
  • Complete response is achieved
  • No injectable lesions remain
  • Disease progression occurs with decline in performance status
  • Intolerable toxicity develops 2
• Maximum treatment duration: Up to 18 months (12 months + additional 6 months for responders) 2

Efficacy Expectations

• Durable response rate: 16.3% overall (vs 2.1% with GM-CSF) 1, 4
• Complete response rate: 11% (vs <1% with GM-CSF) 1
• Response by stage:
  • Stage IIIB/IIIC: 33% durable response rate 1
  • Stage IV-M1a: 16% durable response rate 1
  • Stage IV-M1b/M1c: Minimal effect 1
• Real-world outcomes: Complete local response in 39% and partial response in 18% of patients 5

Side Effect Management

Common adverse events (occurring in ≥20% of patients):

• Fatigue, chills, pyrexia, nausea, flu-like illness, injection-site pain, and vomiting 1, 4

Management approach:

• Most side effects are mild (grade 1-2) and self-limiting 5, 6
• Grade 3-4 toxicities occur in approximately 11% of patients 1
• Treatment-related toxicities include:
  • Injection site reactions (cellulitis, pain, peripheral edema)
  • Systemic toxicities (fatigue, vomiting, flu-like symptoms) 1

Treatment Positioning in Therapeutic Algorithm

T-VEC is positioned as:

1. Not a first-line therapy for most patients with unresectable stage III/IV melanoma 1
2. Primary option for patients with injectable unresectable lesions who are not eligible for or do not desire recommended systemic therapies 1, 3
3. Alternative therapy for patients with in-transit metastases where surgery is not possible 6

Important Clinical Considerations

• Responses may be delayed or occur after initial pseudoprogression, similar to other immunotherapies 6
• Effects are observed in both injected and uninjected lesions (64%/34% of evaluable injected/uninjected non-visceral lesions decreased in size by ≥50%) 6
• T-VEC is no longer recommended for patients with BRAF wild-type disease who have progressed on anti-PD-1 therapy 1
• Combination with checkpoint inhibitors is being investigated with promising early results 7

T-VEC represents a unique treatment option with direct oncolytic effects in injected lesions and systemic immune effects through induction of anti-tumor immunity, making it particularly valuable for patients with earlier-stage unresectable disease who cannot receive or decline systemic therapies.