Immunotherapy in Melanoma: Navigating Special Patient Populations

The landscape of melanoma treatment has undergone a radical transformation over the past decade, primarily due to the advent of immune checkpoint inhibitors (ICIs). These agents, specifically those targeting PD-1, alone or in combination with cytotoxic T-lymphocyte–associated antigen 4 or anti–lymphocyte-activation gene 3, have revolutionized the approach to chemotherapy-resistant metastatic cutaneous melanoma. However, the efficacy and safety of ICIs in special patient populations, historically excluded from clinical trials, remain a complex challenge for dermatology clinicians and oncologists. The Society for Immunotherapy of Cancer recently published insights into the management of patients with preexisting autoimmune disease, solid organ transplant recipients, elderly individuals, those living with HIV, pregnant patients, and those with rare noncutaneous subtypes of melanoma.

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Patients With Altered Immune Systems

ICIs may be considered for those with preexisting autoimmune diseases, with careful risk-benefit analysis. Patients with melanoma whose immune systems are already altered should not be automatically ruled out from receiving ICI therapy. Since immunotherapy holds the potential for curing melanoma, it is advisable to refer such patients to a specialized cancer center for evaluation of treatment options. The decision to start ICI therapy should involve shared decision-making among the patient, health care provider, and collaborative care team, considering the risks and benefits specific to these individuals.

In the case of solid organ transplant recipients diagnosed with melanoma, the decision to pursue ICI therapy should be made through a thorough risk-benefit discussion in consultation with the transplantation team. This involves weighing the potential for long-term melanoma-specific survival against the significant risk of allograft loss, which could necessitate life-supporting interventions such as dialysis or insulin or even lead to death.

For individuals with preexisting autoimmune diseases and melanoma, the decision to begin ICI therapy should be based on a careful risk-benefit discussion, with coordination of care involving relevant specialty providers. This discussion should assess the likelihood of long-term melanoma-specific survival against the risk of a flare-up of the autoimmune disease.

Patients Living With HIV Infection (PLWH)

Increased melanoma risk in patients with HIV necessitates careful consideration of ICIs. Collaboration with infectious disease specialists and initiation of highly active antiretroviral therapy is recommended.

“A systematic review including 73 PLWH with a variety of advanced solid tumors found an [objective response rate] of 27% for ICIs (mostly anti–PD-1 monotherapy) in the melanoma subgroup,” study authors wrote. “Across tumor types, for the 34 patients with known paired pretreatment and posttreatment viral titers available, HIV remained suppressed in 26 of the 28 (93%) individuals with undetectable HIV loads at baseline. Although using ICIs to treat melanoma in PLWH requires close comanagement with an infectious disease specialist, these patients should be given equal consideration to the general population for treatment with ICIs in the standard of care and clinical trial settings.”

Pregnant Patients

Despite documented cases of pregnancies during ICI treatment, initiation during pregnancy is generally discouraged. Clear risk-benefit discussions, adherence to pregnancy prevention, and post-treatment precautions are essential.

Study authors wrote, “For pregnant patients with melanoma, there are no clinical trial data to inform the efficacy or safety of ICIs. Initiation or continuation of ICI treatment in pregnant patients warrants a careful risk-benefit conversation with the patient and the individuals they choose to be involved with their decision-making (eg, family, intimate partner, and friends) along with multidisciplinary evaluation including high-risk obstetrics.”

Managing Noncutaneous Melanoma Subtypes

Dermatology clinicians may see types of noncutaneous melanoma affecting the eyes or mucosal membranes such as the mouth, nose, vagina, or anus. Patients with noncutaneous melanoma should be informed that despite the rarity of these melanoma subtypes, there may be available clinical trial strategies that can lead to prolonged and high-quality survival. For individuals with rare melanoma subtypes, it is advisable to seek referral to a health care provider at an academic medical center.

In the case of advanced rare melanoma subtypes, frontline immunotherapy is recommended, with careful consideration of potential contraindications and toxicities. Molecular mutation testing is recommended for all patients with rare melanoma subtypes. The identification of actionable mutations provides an opportunity for targeted therapy or participation in molecularly directed clinical trials.

Patients with localized uveal melanoma should consider eye-directed therapy at a subspecialty center as a primary treatment option. For patients with mucosal melanoma, a discussion about the risks and benefits of definitive surgical resection as a primary consideration should take place at a specialty care center. The role of immunotherapy is best determined through multidisciplinary evaluation.

Patient Education and Quality of Life Support

Both dermatology and oncology clinicians play a pivotal role in educating patients about ICI mechanisms, adverse effects, and potential benefits. Recognition and management of immune-related adverse events are crucial for sustained treatment and quality of life. Financial burden, fertility considerations, and long-term toxicities are integral components requiring attention and support.

Conclusion

Immunotherapy, a cornerstone in melanoma treatment, has opened new avenues for long-term survival. Ongoing studies, including intratumoral approaches and biomarker research, aim to enhance efficacy and accessibility. The evolving landscape calls for continuous updates to guidelines, emphasizing the importance of clinical trial enrollment and shared decision-making.

In the dynamic field of immunotherapy, dermatology clinicians and oncologists must remain vigilant, adapting their approaches to suit the unique needs of diverse patient populations. The journey toward comprehensive and personalized melanoma care continues, with a commitment to improving outcomes and quality of life for every individual facing this challenging disease.

Reference

Pavlick AC, Ariyan CE, Buchbinder EI, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of melanoma, version 3.0. J Immunother Cancer. 2023;11(10):e006947. doi:10.1136/jitc-2023-006947