Melanoma Immunotherapy: The Long-Term Trial Results

Table of Contents

1. How Checkpoint Drugs Work
2. How the Trials Measure Results
3. CheckMate 067: Design and First Results
4. CheckMate 067 Through Ten Years
5. Long-Term Survivors and Time Off Treatment
6. Relatlimab and Nivolumab: A Third Brake Blocked
7. SWOG S1801: Pembrolizumab Before Surgery
8. KEYNOTE-716: Pembrolizumab After Surgery for Stage II
9. Cell Therapy From the Tumor Itself
10. Serious Immune-Related Side Effects
11. What Is Not Known
12. Key Research Papers
13. Connections
14. Featured Videos

How Checkpoint Drugs Work

T cells, the immune cells that kill infected and abnormal cells, carry built-in brakes on their surface. These brakes, called immune checkpoints, normally stop an immune attack from running out of control and damaging healthy tissue. A 2018 review in Science by two of the field's lead investigators describes the treatment idea: antibodies that block these brakes release T cells that already recognise the tumor but were being held back. The same review states the main premise plainly — the method depends on anti-tumor T cells already being present — and reports that most patients whose tumors respond keep long-lasting control, while about one-third relapse.

Three brakes have drugs approved against them in melanoma:

• Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Ipilimumab blocks this brake. It was the comparison drug in most of the trials on this page.
• Programmed death 1 (PD-1). Nivolumab and pembrolizumab block this brake. The 2015 CheckMate 067 report describes the programmed death 1 and cytotoxic T-lymphocyte-associated antigen 4 blockers as having "complementary activity", which is why they were tested together.
• Lymphocyte-activation gene 3 (LAG-3). Relatlimab blocks this brake. The 2022 trial report describes lymphocyte-activation gene 3 and programmed death 1 as distinct brakes that both contribute to "T-cell exhaustion", the worn-out state of T cells that have faced a tumor for a long time. Relatlimab is given together with nivolumab as one fixed-dose infusion.

Because these drugs take the brakes off the immune system as a whole, not only off the T cells aimed at the tumor, the same mechanism explains their main harm: the immune system can attack healthy organs. That is covered in Serious Immune-Related Side Effects below. The story of how these brakes were discovered is on the Allison & Honjo page.

How the Trials Measure Results

The trials below report several different measures. They are not interchangeable, and a trial can succeed on one and not on another.

• Overall survival: time until death from any cause. It is the hardest measure to move and the slowest to mature.
• Melanoma-specific survival: overall survival with deaths unrelated to melanoma left out. The CheckMate 067 investigators added it because, once people live for many years, some die of other causes.
• Progression-free survival: time until the cancer grows or the person dies, used in advanced melanoma.
• Recurrence-free and event-free survival: used after surgery — time until the melanoma comes back (or, for event-free survival, until any of a list of setbacks, including not being able to have surgery).
• Response rate (objective response): the share of people whose tumors shrank by a set amount on scans.
• Hazard ratio: the rate of the event in one group divided by the rate in the other. A hazard ratio of 0.53 means the event happened at about half the rate; a ratio of 1.00 means no difference. When the range of uncertainty around it (the 95% confidence interval) crosses 1.00, the trial has not shown a difference.
• Grade 3 and grade 4 side effects: severe and life-threatening side effects. Grade 5 is death.

CheckMate 067: Design and First Results

CheckMate 067 is the trial most other melanoma immunotherapy results are measured against. It enrolled 945 people with untreated melanoma that could not be removed by surgery (stage III) or had spread (stage IV), between July 2013 and March 2014. They were split into three equal groups by chance, and neither patients nor doctors knew which group they were in:

• Nivolumab plus ipilimumab (314 people): the trial gave nivolumab 1 mg per kilogram plus ipilimumab 3 mg per kilogram every 3 weeks for four doses, then nivolumab 3 mg per kilogram every 2 weeks.
• Nivolumab alone (316 people): nivolumab 3 mg per kilogram every 2 weeks.
• Ipilimumab alone (315 people): ipilimumab 3 mg per kilogram every 3 weeks for four doses.

Treatment continued until the cancer grew, side effects became unacceptable, or the person withdrew. The first report (2015) gave median progression-free survival of 11.5 months with the combination, 6.9 months with nivolumab alone and 2.9 months with ipilimumab alone. The hazard ratio for progression or death was 0.42 for the combination and 0.57 for nivolumab alone, each against ipilimumab. In people whose tumors carried the programmed death 1 partner protein (PD-L1), both nivolumab groups had a median of 14.0 months; in people whose tumors lacked it, the combination gave 11.2 months against 5.3 months with nivolumab alone.

The cost was in side effects. Treatment-related grade 3 or 4 side effects occurred in 55.0% of the combination group, 16.3% of the nivolumab group and 27.3% of the ipilimumab group. The trial was funded by the manufacturer of nivolumab and ipilimumab.

CheckMate 067 Through Ten Years

The trial reported again at 4, 5, 6.5 and 10 years. The figures below are taken from each report's abstract.

• At 4 years (2018): median overall survival was not yet reached with the combination, 36.9 months with nivolumab and 19.9 months with ipilimumab. The hazard ratio for death was 0.54 for the combination and 0.65 for nivolumab, each against ipilimumab.
• At 5 years (2019): 52% of the combination group, 44% of the nivolumab group and 26% of the ipilimumab group were alive. The report found no sustained fall in health-related quality of life in the two nivolumab groups and no new late side effects.
• At 6.5 years (2022): median overall survival was 72.1, 36.9 and 19.9 months. Survival at 6.5 years depended partly on the tumor's BRAF gene: in people with a BRAF mutation it was 57%, 43% and 25%; in people without one it was 46%, 42% and 22%.
• At 10 years (2025, the final report): median overall survival was 71.9 months with the combination, 36.9 months with nivolumab and 19.9 months with ipilimumab. The hazard ratio for death was 0.53 for the combination and 0.63 for nivolumab, each against ipilimumab.

The final report also gave melanoma-specific survival. With the combination, the median was more than 120 months — it was never reached — with 37% of patients alive at the end of the trial, according to the abstract. The median was 49.4 months with nivolumab and 21.9 months with ipilimumab.

The most quoted figure from the final report is about people who did well early. Among those who were alive and whose melanoma had not grown at 3 years, 10-year melanoma-specific survival was 96% with the combination, 97% with nivolumab and 88% with ipilimumab. In other words, in this trial, reaching 3 years without progression was followed by very few melanoma deaths over the next seven years, whichever drug had been given.

Two limits are worth stating. First, the comparison the trial was designed to test was each nivolumab group against ipilimumab; the combination against nivolumab alone was analysed only descriptively, so the trial does not prove the combination is better than nivolumab alone. Second, the median of 71.9 months still means about half the people on the combination had died by about six years.

Long-Term Survivors and Time Off Treatment

Many people in these trials stopped their drug, either because side effects forced them to or because the planned course ended, and some lived for long stretches without needing another cancer treatment.

In the 6.5-year CheckMate 067 report, among people who stopped treatment, the median time before they started any further treatment was 27.6 months after the combination, 2.3 months after nivolumab and 1.9 months after ipilimumab.

A 2019 pooled analysis of 1,077 patients from CheckMate 067 and the smaller CheckMate 069 trial created a measure called treatment-free survival: time alive after the checkpoint drug stopped and before any next cancer treatment, split into time with and without serious side effects. At 36 months, 47% of people given the combination, 37% given nivolumab and 15% given ipilimumab were alive without having started another treatment. Averaged over the 36 months, treatment-free time was 11.1 months with the combination, 4.6 months with nivolumab and 8.7 months with ipilimumab. Time with grade 3 or higher side effects made up a small part of it — 3% of the 36-month period after the combination, 1% after nivolumab and under 1% after ipilimumab.

Ipilimumab scored higher than nivolumab on treatment-free time because ipilimumab was given for only four doses, so its patients came off treatment early, not because they did better overall; nivolumab alone was continued for longer. The measure describes time off treatment, not cure.

Relatlimab and Nivolumab: A Third Brake Blocked

Advanced melanoma: RELATIVITY-047

The RELATIVITY-047 trial compared relatlimab plus nivolumab with nivolumab alone in 714 people with untreated melanoma that had spread or could not be removed (355 and 359 people). The trial gave nivolumab 480 mg plus relatlimab 160 mg, or nivolumab 480 mg alone, into a vein every 4 weeks. Its main measure was progression-free survival judged by reviewers who did not know the treatment.

• First report (2022): median progression-free survival was 10.1 months with the combination and 4.6 months with nivolumab (hazard ratio 0.75). At 12 months, 47.7% and 36.0% were progression-free. Grade 3 or 4 treatment-related side effects occurred in 18.9% and 9.7%.
• Overall survival, first look (2023): the hazard ratio for death was 0.80, with a confidence interval of 0.64 to 1.01 and P = 0.059. The trial had set P ≤ 0.043 as its bar, so overall survival did not reach statistical significance. Response rates were 43.1% and 32.6%; grade 3 or 4 treatment-related side effects were 21.1% and 11.1%.
• 4-year update (2025): 30.6% of the combination group and 23.6% of the nivolumab group were progression-free; 52.0% and 42.8% were alive; melanoma-specific survival was 59.7% and 49.6%; response rates were 43.9% and 33.4%. The authors call these descriptive analyses.
• 5-year analysis (2026): with at least 57.3 months of follow-up, the hazard ratios favored the combination for progression-free survival (0.77), overall survival (0.78, confidence interval 0.64 to 0.95) and melanoma-specific survival (0.71). The melanoma-specific analysis was added after the trial began (post hoc).

The 2026 report states that relatlimab plus nivolumab is approved for advanced melanoma on the basis of this trial. The trial compared the combination with nivolumab alone; it did not compare it with nivolumab plus ipilimumab head to head. A comparison against the CheckMate 067 combination relies on indirect methods across different trials.

After surgery: RELATIVITY-098 (a null result)

The same combination was tested after complete surgical removal of stage III or IV melanoma. RELATIVITY-098 assigned 547 people to relatlimab plus nivolumab and 546 to nivolumab alone, for up to one year. There was no difference in recurrence-free survival: the hazard ratio was 1.01 (confidence interval 0.83 to 1.22; P = 0.928). Because the main measure failed, overall survival was not tested. The investigators suggest a reason from laboratory measurements: people with no visible tumor left had fewer lymphocyte-activation gene 3-carrying T cells in the blood than people with advanced disease.

SWOG S1801: Pembrolizumab Before Surgery

The SWOG S1801 trial, funded by the U.S. National Cancer Institute and the manufacturer of pembrolizumab, asked whether giving some doses of pembrolizumab before surgery works better than giving them all after it. It enrolled 313 people with stage IIIB to IVC melanoma that could be seen and measured and could be removed by surgery.

• Before-and-after group (154 people): three doses of pembrolizumab, then surgery, then 15 more doses.
• After-only group (159 people): surgery, then pembrolizumab 200 mg into a vein every 3 weeks for 18 doses (about one year).

The main measure was event-free survival. An "event" included the cancer growing or side effects that prevented surgery, being unable to remove all visible disease, problems that delayed the start of treatment after surgery beyond 84 days, the melanoma coming back, or death. At a median follow-up of 14.7 months, event-free survival was significantly longer in the before-and-after group. At 2 years, 72% of that group and 49% of the after-only group were event-free. Grade 3 or higher treatment-related side effects occurred in 12% and 14%, and no new kinds of side effect were found.

Three limits are reported. S1801 was a phase 2 trial, not a phase 3 trial. Its abstract reports event-free survival but no overall survival result. And a 2024 critique by two outside researchers argued that the rule for assigning events, and different rates of early drop-out from follow-up between the two groups, could have exaggerated the benefit; they wrote that the result needs confirming in a phase 3 trial. The Skin Cancer page covers a separate phase 3 trial of two drugs given before surgery.

KEYNOTE-716: Pembrolizumab After Surgery for Stage II

Stage II melanoma has not spread to the lymph nodes, but thick tumors (stages IIB and IIC) can still come back. KEYNOTE-716 assigned 976 people aged 12 or older, whose stage IIB or IIC melanoma had been fully removed and whose sentinel lymph node was clear, to pembrolizumab (487) or a placebo (489). The trial gave pembrolizumab 200 mg (2 mg per kilogram for children) every 3 weeks for 17 doses, about one year. It ran at 160 centers in 16 countries and was funded by the manufacturer.

• First and second interim analyses (2022): at a median of about 14 months, 11% of the pembrolizumab group and 17% of the placebo group had a recurrence or died (hazard ratio 0.65). At about 21 months the figures were 15% and 24% (hazard ratio 0.61).
• Final distant-spread analysis (2024): at a median of 39.4 months, 84.4% of the pembrolizumab group and 74.7% of the placebo group were free of spread to distant organs at 36 months (hazard ratio 0.59); recurrence-free survival at 36 months was 76.2% and 63.4%.
• 4-year analysis (2025): at a median of 52.8 months, 71.3% of the pembrolizumab group and 58.3% of the placebo group were recurrence-free at 48 months (hazard ratio 0.62), and 81.0% and 70.1% were free of distant spread. This analysis was planned after the trial began (post hoc).

Two further 4-year findings matter. First, people in the placebo group whose melanoma came back could switch to pembrolizumab. The measure that counts survival without a second progression after that switch had a hazard ratio of 0.75 with a confidence interval of 0.56 to 1.01 — it crossed 1.00, so it did not show a clear difference (82.5% versus 76.7% at 48 months). Second, the abstracts read for this page give no overall survival result, so whether giving pembrolizumab straight after surgery helps people live longer than giving it at recurrence is not shown by them.

A 2026 analysis of the same trial counted new skin cancers. New skin cancers were diagnosed in 7.6% of the pembrolizumab group and 11.5% of the placebo group; new invasive melanomas in 2.5% and 1.8%, which the authors report as no difference. Severe immune-related skin reactions occurred in 3.3% and 0.6%. In the first report, grade 3 or 4 treatment-related side effects occurred in 16% of the pembrolizumab group and 4% of the placebo group.

Cell Therapy From the Tumor Itself

Tumor-infiltrating lymphocyte (TIL) therapy takes a different route. A piece of the person's own tumor is removed by surgery, the T cells living inside it are grown into billions in a laboratory, and they are infused back. Before the infusion the person receives chemotherapy (cyclophosphamide and fludarabine) to empty out existing immune cells, and after it, high-dose interleukin-2 to help the cells multiply.

The phase 3 trial against ipilimumab

The only phase 3 trial so far, published in 2022 and funded by the Dutch Cancer Society and others, randomly assigned 168 people with stage IIIC or IV melanoma that could not be removed to tumor-infiltrating lymphocyte therapy (84) or ipilimumab 3 mg per kilogram (84). In 86% the melanoma had already stopped responding to programmed death 1 drugs. The cell product in this trial was made by the academic centers running it, not the commercial product described below.

• Median progression-free survival: 7.2 months with the cell therapy and 3.1 months with ipilimumab (hazard ratio 0.50).
• Response rate: 49% and 21%.
• Median overall survival: 25.8 months and 18.9 months. The abstract does not report this difference as statistically tested.
• Grade 3 or higher treatment-related side effects: in every patient who received the cell therapy, mainly low blood counts caused by the chemotherapy, and in 57% of those given ipilimumab.

Lifileucel and its accelerated approval

On February 16, 2024 the U.S. Food and Drug Administration announced its approval of lifileucel, which it called the first cellular therapy for adults with melanoma that cannot be removed or has spread, after a programmed death 1 drug and, if the tumor carries a BRAF V600 mutation, a BRAF drug with or without a MEK drug. The approval used the Accelerated Approval pathway, which rests on a measure "reasonably likely" to predict benefit — here the response rate and how long responses lasted — and the U.S. Food and Drug Administration stated that a confirmatory trial was ongoing. Among 73 people treated at the recommended dose, 31.5% responded (4.1% complete, 27.4% partial). The label carries a boxed warning for prolonged severe low blood counts, severe infection, heart problems, worsening breathing or kidney function, and fatal treatment-related complications.

The study behind it, C-144-01, was a single-group phase 2 trial with no comparison group. Its pooled report of 153 people, who had received a median of three earlier treatments, gave a response rate of 31.4%, median progression-free survival of 4.1 months and median overall survival of 13.9 months. The most common grade 3 or 4 side effects were low platelets (76.9%), anemia (50.0%) and fever with low white cells (41.7%). At 5 years, 19.7% were alive; the median response lasted 36.5 months, and 31.3% of the people who responded still had a response at the 5-year assessment. The authors report that side effects fell quickly within 2 weeks of the infusion.

Serious Immune-Related Side Effects

Because checkpoint drugs release the immune system's brakes in general, the immune system can attack the bowel, liver, lungs, skin, hormone glands, heart and nerves. The trials above give the overall rates:

• CheckMate 067, 4-year report: treatment-related grade 3 or 4 side effects in 59% of the combination group, 22% of the nivolumab group and 28% of the ipilimumab group. The most common grade 3 events were diarrhea (9% with the combination) and colitis (7% with ipilimumab). Across the trial there were four treatment-related deaths: two with the combination (heart muscle disease and liver necrosis), one with nivolumab and one with ipilimumab (a perforated colon).
• RELATIVITY-047: grade 3 or 4 treatment-related side effects in 21.1% with relatlimab plus nivolumab and 11.1% with nivolumab alone.
• KEYNOTE-716 and S1801 (pembrolizumab after or around surgery): 16% against 4% with placebo, and 12% against 14% between the two pembrolizumab schedules.

Hormone glands: damage that can be permanent

A 2018 analysis of 38 randomized trials covering 7,551 patients found that thyroid problems (both underactive and overactive thyroid) were most frequent with combined programmed death 1 and cytotoxic T-lymphocyte-associated antigen 4 blockade. Inflammation of the pituitary gland (hypophysitis) was less likely with programmed death 1 drugs than with ipilimumab, and more likely with the combination. The authors note that, if not recognised promptly, these hormone problems can be life-threatening.

A 2026 review of 22 patients with checkpoint-related pituitary inflammation at one specialist clinic (77% with metastatic melanoma, 68% given ipilimumab plus nivolumab) found it began a median of 13 weeks into treatment, after about the third dose. Every patient lost the pituitary's signal to the adrenal glands (secondary adrenal insufficiency), and none recovered it during follow-up, so lifelong steroid replacement was needed. Underactive thyroid from the pituitary recovered in 33% and low sex hormones in 67%. New type 1 diabetes developed in 18%, three with diabetic ketoacidosis. Headache, fatigue, nausea and low blood sodium were the most common signs at presentation. This is a small, single-centre series, so its percentages are uncertain.

Deaths from side effects

A 2018 analysis combining a World Health Organization drug-safety database, records from seven academic centers and 112 published trials (19,217 patients) found fatal side effects in 0.36% of people given programmed death 1 drugs, 1.08% given cytotoxic T-lymphocyte-associated antigen 4 drugs and 1.23% given the two combined. Deaths came early: a median of 14.5 days after starting the combination and 40 days after starting either drug alone. Heart muscle inflammation (myocarditis) was the most lethal, with 39.7% of reported cases fatal; colitis and hormone-gland events were fatal in 2% to 5% of reported cases. With the combination, colitis (37%) and myocarditis (25%) were the most common causes of death.

What Is Not Known

• Who will respond. The trials report averages. In CheckMate 067 about half of the people on the combination had died by about six years, and the 2018 review notes that about one-third of responders later relapse. No test in these abstracts reliably picks out the people who will benefit; the 2026 RELATIVITY-047 report links lymphocyte-activation gene 3-carrying T cells to outcomes only as a hypothesis.
• Combination or single drug, head to head. CheckMate 067 was not designed to prove the combination better than nivolumab alone, and no trial read for this page compared relatlimab plus nivolumab directly with nivolumab plus ipilimumab.
• Survival after early treatment. The KEYNOTE-716 and S1801 abstracts read for this page report recurrence and event measures, not overall survival. Whether early treatment lengthens life, rather than delaying a recurrence that later treatment could also handle, is not shown.
• Not every combination works after surgery. Relatlimab plus nivolumab, which helped in advanced melanoma, did nothing extra after complete surgery in RELATIVITY-098.
• Long-term harms in younger survivors. Permanent hormone loss is documented, but most follow-up of side effects comes from people with advanced melanoma; less is published on lifelong consequences in people treated for stage II disease, who may live for decades.
• Cell therapy's survival benefit. The phase 3 cell-therapy trial measured progression-free survival as its main result; the lifileucel approval rests on response rate in a single-group trial, with a confirmatory trial ongoing at the time of approval.
• Who was in the trials. In KEYNOTE-716, 90% of participants were White, so its results come mostly from White patients.

Key Research Papers

1. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350-1355. PubMed PMID: 29567705
2. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. New England Journal of Medicine. 2015;373(1):23-34. PubMed PMID: 26027431
3. Hodi FS, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Cowey CL, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncology. 2018;19(11):1480-1492. PubMed PMID: 30361170
4. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, et al. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. New England Journal of Medicine. 2019;381(16):1535-1546. PubMed PMID: 31562797
5. Wolchok JD, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, et al. Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma. Journal of Clinical Oncology. 2022;40(2):127-137. PubMed PMID: 34818112
6. Wolchok JD, Chiarion-Sileni V, Rutkowski P, Cowey CL, Schadendorf D, Wagstaff J, et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. New England Journal of Medicine. 2025;392(1):11-22. PubMed PMID: 39282897
7. Regan MM, Werner L, Rao S, Gupte-Singh K, Hodi FS, Kirkwood JM, et al. Treatment-Free Survival: A Novel Outcome Measure of the Effects of Immune Checkpoint Inhibition-A Pooled Analysis of Patients With Advanced Melanoma. Journal of Clinical Oncology. 2019;37(35):3350-3358. PubMed PMID: 31498030
8. Tawbi HA, Schadendorf D, Lipson EJ, Ascierto PA, Matamala L, Castillo Gutiérrez E, et al. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. New England Journal of Medicine. 2022;386(1):24-34. PubMed PMID: 34986285
9. Long GV, Stephen Hodi F, Lipson EJ, Schadendorf D, Ascierto PA, Matamala L, et al. Overall Survival and Response with Nivolumab and Relatlimab in Advanced Melanoma. NEJM Evidence. 2023;2(4):EVIDoa2200239. PubMed PMID: 38320023
10. Lipson EJ, Stephen Hodi F, Tawbi H, Schadendorf D, Ascierto PA, Matamala L, et al. Nivolumab plus relatlimab in advanced melanoma: RELATIVITY-047 4-year update. European Journal of Cancer. 2025;225:115547. PubMed PMID: 40513285
11. Long GV, Dolfi S, Hodi FS, Lipson EJ, Schadendorf D, Ascierto PA, et al. Relatlimab plus nivolumab versus nivolumab for advanced melanoma: 5-year survival and biomarker analyses of the phase 3 RELATIVITY-047 trial. Nature Medicine. 2026; online ahead of print. PubMed PMID: 42926136
12. Long GV, Garnett-Benson C, Dolfi S, Ascierto PA, Guo J, Tarhini AA, et al. Adjuvant nivolumab and relatlimab in stage III/IV melanoma: the randomized phase 3 RELATIVITY-098 trial. Nature Medicine. 2025;31(12):4301-4309. PubMed PMID: 41109920
13. Patel SP, Othus M, Chen Y, Wright GP Jr, Yost KJ, Hyngstrom JR, et al. Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma. New England Journal of Medicine. 2023;388(9):813-823. PubMed PMID: 36856617
14. Olivier T, Prasad V. Neoadjuvant followed by adjuvant pembrolizumab in melanoma: time biases in the data analysis of the SWOG S1801 trial. Translational Oncology. 2024;45:101959. PubMed PMID: 38621314
15. Luke JJ, Rutkowski P, Queirolo P, Del Vecchio M, Mackiewicz J, Chiarion-Sileni V, et al. Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial. Lancet. 2022;399(10336):1718-1729. PubMed PMID: 35367007
16. Luke JJ, Ascierto PA, Khattak MA, de la Cruz Merino L, Del Vecchio M, Rutkowski P, et al. Pembrolizumab Versus Placebo as Adjuvant Therapy in Resected Stage IIB or IIC Melanoma: Final Analysis of Distant Metastasis-Free Survival in the Phase III KEYNOTE-716 Study. Journal of Clinical Oncology. 2024;42(14):1619-1624. PubMed PMID: 38452313
17. Luke JJ, Ascierto PA, Khattak MA, Rutkowski P, Del Vecchio M, Spagnolo F, et al. Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Long-term follow-up, crossover, and rechallenge with pembrolizumab in the phase III KEYNOTE-716 study. European Journal of Cancer. 2025;220:115381. PubMed PMID: 40198940
18. Leachman SA, Luke JJ, Ascierto PA, Long GV, Khattak MA, Rutkowski P, et al. Adjuvant Pembrolizumab for Stage IIB or IIC Melanoma: A Secondary Analysis of a Randomized Clinical Trial. JAMA Network Open. 2026;9(2):e2559603. PubMed PMID: 41701495
19. Rohaan MW, Borch TH, van den Berg JH, Met Ö, Kessels R, Geukes Foppen MH, et al. Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma. New England Journal of Medicine. 2022;387(23):2113-2125. PubMed PMID: 36477031
20. Chesney J, Lewis KD, Kluger H, Hamid O, Whitman E, Thomas S, et al. Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study. Journal for ImmunoTherapy of Cancer. 2022;10(12):e005755. PubMed PMID: 36600653
21. Medina T, Chesney JA, Kluger HM, Hamid O, Whitman ED, Cusnir M, et al. Long-Term Efficacy and Safety of Lifileucel Tumor-Infiltrating Lymphocyte Cell Therapy in Patients With Advanced Melanoma: A 5-Year Analysis of the C-144-01 Study. Journal of Clinical Oncology. 2025;43(33):3565-3572. PubMed PMID: 40454684
22. Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, et al. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA Oncology. 2018;4(2):173-182. PubMed PMID: 28973656
23. Mathara Diddhenipothage SAD, Warden J, Herbert K, Pofi R, Joseph R, Coupe N, et al. Immune Checkpoint Inhibitor Therapy Induced Hypophysitis; A Tertiary Care Centre Experience; Highlighting Detection, Treatment Outcomes and Long Term Endocrinopathies and Recovery. Clinical Endocrinology. 2026;105(3):331-338. PubMed PMID: 41879139
24. Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F, et al. Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA Oncology. 2018;4(12):1721-1728. PubMed PMID: 30242316
25. U.S. Food and Drug Administration. FDA Approves First Cellular Therapy to Treat Patients with Unresectable or Metastatic Melanoma. News release, February 16, 2024. fda.gov press announcement

PubMed Topic Searches

1. PubMed: nivolumab plus ipilimumab, long-term survival in melanoma
2. PubMed: relatlimab and nivolumab in melanoma
3. PubMed: immunotherapy before surgery in melanoma
4. PubMed: pembrolizumab after surgery for stage II melanoma
5. PubMed: tumor-infiltrating lymphocyte therapy in melanoma
6. PubMed: permanent hormone damage after checkpoint drugs

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Connections

• Melanoma — the main topic page: signs, stages and all treatments
• Skin Cancer — all skin cancers, including newer trials of treatment before surgery
• Uveal Melanoma — melanoma of the eye, which behaves differently
• Merkel Cell Carcinoma — another skin cancer treated with checkpoint drugs
• Allison & Honjo — the scientists behind the checkpoint discoveries
• Ultraviolet Radiation — the main cause of melanoma's many mutations
• Dermatology — the skin diseases section

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