Treatment history

Melanoma treatment development timeline

Discoveries and approvals show how the field changed. They do not decide which treatment fits a person, whether someone is eligible, or what order is right.

1. local therapy

   pre-2000s: Surgery and pathology remain the foundation for localized melanoma

   Removing melanoma and reading the pathology report remain central for early-stage and selected local situations.

   What changed

   Modern systemic options did not remove the need for careful staging, margins, lymph-node questions, and pathology review.

   Do not infer

   Surgery alone does not answer whether surveillance, adjuvant therapy, radiation, systemic therapy, or trial discussion is needed.

   clinical-trials

   Sources with the medical details

   1. Melanoma Treatment (PDQ) - Patient Version. Accessed 2026-05-20.
   2. Melanoma Treatment (PDQ) - Health Professional Version. Accessed 2026-05-20.
2. immunotherapy

   2011: Ipilimumab opens the checkpoint inhibitor era in melanoma

   A CTLA-4 checkpoint inhibitor became an approved melanoma immunotherapy option.

   What changed

   Melanoma treatment shifted from mostly chemotherapy/local approaches toward immune checkpoint strategies.

   Do not infer

   Checkpoint therapy can have serious immune side effects and does not fit every patient or every sequence.

   ipilimumabnivolumab-ipilimumab

   Sources with the medical details

   1. FDA approval context for ipilimumab in unresectable or metastatic melanoma. Accessed 2026-05-21.
   2. Drugs Approved for Melanoma. Accessed 2026-05-20.
3. targeted therapy

   2011: BRAF-targeted therapy arrives with vemurafenib

   A drug targeting BRAF V600-mutant melanoma showed how mutation testing could change the treatment conversation.

   What changed

   Mutation results became more directly tied to treatment categories in melanoma.

   Do not infer

   BRAF drugs are not for NRAS-only melanoma unless the report also documents qualifying BRAF mutation.

   melanoma-braf-v600braf-mek-combinationsvemurafenib-cobimetinib

   Sources with the medical details

   1. NCI: Vemurafenib. Accessed 2026-05-21.
   2. Melanoma Treatment (PDQ) - Health Professional Version. Accessed 2026-05-20.
4. immunotherapy

   2014-2015: PD-1 inhibitors and checkpoint combinations expand

   Pembrolizumab and nivolumab became major PD-1 checkpoint inhibitor names, and nivolumab plus ipilimumab expanded the combination conversation.

   What changed

   Families increasingly heard PD-1, CTLA-4, response duration, immune toxicity, and sequencing language.

   Do not infer

   PD-1 drugs are not MEK inhibitors, and a prior PD-1 failure changes later trial and treatment questions.

   nivolumab-pembrolizumab-pd1nivolumabpembrolizumabnivolumab-ipilimumab

   Sources with the medical details

   1. NCI: Pembrolizumab for Advanced Melanoma. Accessed 2026-05-21.
   2. NCI: FDA expands nivolumab uses, including nivolumab plus ipilimumab in melanoma. Accessed 2026-05-21.
   3. Melanoma Treatment (PDQ) - Patient Version. Accessed 2026-05-20.
5. local therapy

   2015: T-VEC adds an injectable/local immunotherapy lane

   An intralesional therapy became part of selected melanoma local-treatment discussions.

   What changed

   Local therapy could include more than surgery or radiation in selected lesion-specific situations.

   Do not infer

   Injectable local therapy is not the same as a whole-body systemic treatment.

   t-vec

   Sources with the medical details

   1. Drugs Approved for Melanoma. Accessed 2026-05-20.
   2. Melanoma Treatment (PDQ) - Patient Version. Accessed 2026-05-20.
6. immunotherapy

   2022: Nivolumab plus relatlimab adds PD-1 + LAG-3 language

   A checkpoint combination using PD-1 and LAG-3 became part of U.S. melanoma source context.

   What changed

   Families may now hear LAG-3 alongside PD-1 and CTLA-4.

   Do not infer

   It does not automatically replace PD-1 alone, nivolumab plus ipilimumab, targeted therapy, TIL, or trials.

   nivolumab-relatlimab

   Sources with the medical details

   1. FDA approval of Opdualag (nivolumab and relatlimab-rmbw) for unresectable or metastatic melanoma. Accessed 2026-05-20.
   2. Drugs Approved for Melanoma. Accessed 2026-05-20.
7. cell therapy

   2024: Lifileucel / TIL therapy receives accelerated approval

   A tumor-infiltrating lymphocyte therapy became a U.S. approved melanoma option in a specific post-treatment context.

   What changed

   Cell therapy became part of the melanoma options vocabulary outside trials for selected adults.

   Do not infer

   TIL therapy is not broadly available everywhere and has specific prior-treatment, center, and patient-fitness requirements.

   lifileucel-til

   Sources with the medical details

   1. FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. Accessed 2026-05-20.
   2. Drugs Approved for Melanoma. Accessed 2026-05-20.
8. targeted therapy

   2024: China conditionally approves tunlametinib for NRAS-mutant advanced melanoma context

   A China-specific MEK inhibitor became especially important for MatchMedi because of the NRAS melanoma lived context.

   What changed

   NRAS melanoma families may encounter country-specific options that do not map cleanly to U.S. availability.

   Do not infer

   Tunlametinib should not be assumed available outside China, and tunlametinib plus nivolumab remains unresolved as exact melanoma evidence.

   tunlametinib-hl-085tunlametinib-nivolumab-unresolved

   Sources with the medical details

   1. Tunlametinib Capsules approved with conditions for marketing by China NMPA. Accessed 2026-05-20.
   2. NCT06008106: Comparing Tunlametinib Capsules and Combination Chemotherapy in Advanced NRAS-mutant Melanoma. Accessed 2026-05-20.