Patients With Advanced, Recurrent Melanoma May Experience Lasting AEs From ICM Therapy

Patients with advanced melanoma can still experience adverse effects (AEs) from immune checkpoint modulator (ICM) therapy a year after their treatment initiation, according to a recent study published in Supportive Care in Cancer. These findings stress the need for ongoing adverse effect management and screening in long-term survivors of advanced melanoma.

In the US, advanced melanoma affects an estimated 66,000 people.¹ ICM therapy has altered the trajectory of this cancer, drastically improved survival rates, and become the standard of care (SOC) for immunotherapy in this area. Despite their beneficial impacts on patient outcomes, immune-related AEs (irAEs) occur at rates over 90% in patients who receive this treatment.

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These effects can range in severity. For example, patients administered pembrolizumab, an approved PD-1 inhibitor (anti–PD-1), have reported a myriad of added symptoms: from rash and fatigue to hepatotoxicity, hypothyroidism, colitis, and more.² Furthermore, this class of drug has also impacted patients’ appetites and contributed to gastrointestinal issues, and pneumonitis.¹

The authors of the present study point to prior trials that demonstrate the long-term impact and experience of treatment-related irAEs; however, they add that many of these findings stem from randomized clinical trials, which limits their generalizability due to the lack of patient diversity, younger cohorts, and healthier patients who typically participate in these studies. As a result, data on ICM therapy as an SOC in advanced or recurrent melanoma are insufficient.

Patient-reported outcomes (PROs) have added a lot of clinical value that can guide health care approaches and inform clinicians and patients about what certain treatments entail. Therefore, to address the gaps in knowledge about ICM therapy in advanced or recurrent melanoma, researchers used patient-reported questionnaires and interviews to gather quantitative data on irAEs after 1 year of this treatment.

Eighty patients were eligible to participate, 25% of whom completed a semistructured interview about their experiences with ICM therapy and advanced or recurrent melanoma in addition to their questionnaire. The Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM) and European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire were administered as part of the survey.

The participants had an average age of 67 years, were largely non-Hispanic White (97%), and most commonly had a history of single agent nivolumab in ICM therapy (64%). During the study, 24% of patients were currently receiving treatment.

After questionnaire responses, 98% of participants reported experiencing at least 1 of the 46 AEs surveyed in the FACT-ICM. Of this group, 80% deemed their AE to be “moderate or worse,” 60% gave ratings of “severe or worse”, and 32% reported “very severe” for at least 1 AE. Fatigue (38%) and aching joints (43%) were among the most prevalent AEs reported as “moderate or worse.”

Significant associations were seen between effects such as fatigue, aching joints and muscles, skin dryness, frequent urination, insomnia, nasal congestion, itching, memory problems, numbness/tingling of the hands or feed, and patients’ quality of life reports (P < .01). These results, the authors noted, suggest that the presence of more severe irAEs contribute to a worsened quality of life.

The semistructured interviews revealed 5 themes patients focused on in regard to long-term effects of ICM therapy: lasting fatigue or declines in functioning, minimal AEs, thyroid and pituitary dysfunction, hard to manage skin conditions, and that the cancer treatment was worth the AEs —although a participant responded they would have preferred to be informed about the potential effects, even though that knowledge would not have influenced her decision to pursue treatment.

“A unique contribution of our study was the integration of mixed-methods findings from long-term PROs of ICM treatments. Despite nearly the entire sample acknowledging immune-related side effects occurring within the past week, the qualitative themes suggested diverse perspectives of the impact of these side effects on life after treatment with ICM,” the authors wrote.

Reflecting on the variability of patient experiences, the authors concluded by emphasizing the need for further research that utilizes longitudinal data and larger cohorts to develop better understandings for which patients carry increased risks for lasting and negative effects from ICM therapy.

References

1. Tometich DB, Geiss C, Maconi ML, et al. Patient reported outcomes and patient experiences of immune checkpoint modulators for advanced or recurrent melanoma: a mixed methods study. Support Care Cancer. 2024;32(6):330. doi:10.1007/s00520-024-08538-8

2. Wang Y, Zhang H, Liu C, et al. Immune checkpoint modulators in cancer immunotherapy: recent advances and emerging concepts. J Hematol Oncol. 2022;15(1):111. doi:10.1186/s13045-022-01325-0