The Immunotherapy Revolution – ESMO Lifetime Achievement Award Winner Prof. John Haanen and His Story

A Turning Point in Melanoma Treatment

Recent innovations in melanoma treatment mark an important milestone in cancer care. At the 2024 ESMO Congress, the Lifetime Achievement Award was presented to the Netherlands Cancer Institute's Prof. John Haanen, one of the leading researchers in the immunotherapy revolution in melanoma treatment. Haanen's contributions to cancer immunotherapy have brought hope to patients with melanoma.

Accounting for approximately 5% of all skin cancers, melanoma is an aggressive cancer originating in melanocytes, the skin's pigment-producing cells. Before immunotherapy, treatment options were limited, particularly for metastatic (stage 4) melanoma, and only 1 in every 20 patients survived for 5 years. We were all delighted to see this rate rise above 50%, particularly with combination immunotherapy.

Beginning Melanoma Research: Bringing Hope to Patients

A turning point in Prof. Haanen's career was accepting a position at the Netherlands Cancer Institute approximately 25 years ago. He took the position to develop effective treatments for immunogenic diseases, which can be targeted by the immune system, such as melanoma and kidney cancer. Haanen recalls that melanoma treatment options were very limited at the time: "One-year survival rates for patients with metastatic melanoma were very low, and the treatment options available to us were inadequate." This began to change with research into immune checkpoint inhibitors.

In 2007-2008, Haanen and his team investigated immune checkpoint inhibitors that block CTLA-4, a molecule regulating the immune system, by joining clinical trials. These new treatment strategies began to produce long-term responses in melanoma, an achievement considered a revolutionary development in immunotherapy.

Immunotherapy Is Extending Survival

Melanoma treatment has transformed dramatically since the beginning of Haanen's career. Where only palliative care was once available, patients can now be offered long-term survival and, in some cases, even potentially curative treatments.

Prof. Haanen highlights the CheckMate 067 trial's 7.5-year follow-up results. Median overall survival with combined nivolumab and ipilimumab was 72.1 months, compared with 36.9 months and 19.9 months when the medicines were used alone, respectively. The 10-year follow-up results will be presented at the ESMO 2024 Congress.

The Challenges of Immunotherapy: Managing Side Effects

Although immunotherapy offers promising cancer treatment outcomes, it also brought challenges. Haanen notes that immune-related side effects were initially a new experience for scientists. Extensive research was needed to learn how to manage effects such as fatigue, skin rash and bowel problems. Haanen developed clinical guidelines to address these challenges and make immunotherapies safer and more manageable.

Neoadjuvant Treatment: Success Before Surgery

Prof. Haanen also emphasizes the importance of neoadjuvant treatment, given before surgery, in melanoma. In a clinical trial he initiated at the Netherlands Cancer Institute, patients with stage 3 BRAF-mutant disease received BRAF/MEK inhibitors before surgery. Surgeons achieved complete (R0) resection, providing the first demonstration of the effectiveness of neoadjuvant treatment. This approach improved patients' postoperative survival. Haanen's colleague Christian Blank took it further with immunotherapy, achieving long-term success.

Tumor-Infiltrating Lymphocytes: A Groundbreaking Approach in Melanoma

Developed by Steven A. Rosenberg, tumor-infiltrating lymphocyte (TIL) therapy was advanced further by Prof. Haanen and his Danish colleagues. A phase III trial showed that TIL therapy significantly improved progression-free survival compared with ipilimumab. This treatment is now used as standard care in the Netherlands and Denmark, and work toward EMA approval is ongoing. Haanen notes that studies are continuing to explore TIL therapy in other cancers.

The Future: New Treatments and Innovations

According to Prof. Haanen, the next step in melanoma treatment should be to improve cell therapy effectiveness and reduce side effects. The high-dose chemotherapy and cytokine treatments used in TIL therapy are highly toxic. Haanen emphasizes that reducing these toxicities could make treatment available to a broader population, including older patients and those with other illnesses.

Insights from TILs may enable the targeting of specific T cells that act on the immune system. This suggests that, in the future, T cells collected from a patient's blood could be genetically modified to create a more effective TIL product.

Finally, Prof. Haanen stresses the need for new options for patients who do not respond to ipilimumab and nivolumab. Biomarkers may also help determine which treatments will benefit patients most. Research into oncolytic viruses and mRNA vaccines represents other promising areas that could revolutionize cancer care.

Conclusion: Melanoma Research Continues to Push the Boundaries

Prof. John Haanen may have been honored with ESMO's Lifetime Achievement Award, but melanoma research continues at full pace. Much remains to be done to expand the limits of immunotherapy, find new treatments and minimize side effects. The coming years of melanoma research appear likely to bring patients more hope and more effective treatment options.