Medbrief

Do Low-Grade Toxicities Affect Melanoma Treatment Success?

Edited by Gargi Mukherjee

TOPLINE:

Among patients with stage III melanoma who received adjuvant pembrolizumab, more than 50% experienced low-grade toxicities. The results of such toxicities included patients discontinuing treatment, being hospitalized, and needing immunosuppression.

METHODOLOGY:

  • Immunotherapy reduces the risk for recurrence of melanoma, but it is associated with immune-related adverse events (irAEs), including both high-grade and low-grade toxicities, which can significantly affect patients’ quality of life.
  • Researchers conducted a retrospective analysis to assess the effect of low-grade toxicities among 142 patients with stage III melanoma (median age at diagnosis, 65 years) who received adjuvant pembrolizumab between December 2019 and December 2022.
  • They analyzed data on toxicity, treatment discontinuation, hospital admission, disease progression, and other aspects.
  • Overall, 47% completed a 1-year course of adjuvant pembrolizumab. The median follow-up duration was 28 months, and the median recurrence-free survival duration was 36.2 months.

TAKEAWAY:

  • Among 142 patients, 70% experienced irAEs, of whom 51% experienced only low-grade toxicities (grades 1-2) and the remaining experienced high-grade toxicities (grades 3-4).
  • Among patients with only low-grade toxicities, 31% discontinued treatment and 33% needed immunosuppressive treatment.
  • The rate of early treatment discontinuation was significantly higher in patients aged 65 years or older than in patients younger than 65 years (66% vs 38%, P < .001). Among patients with only low-grade toxicities who discontinued treatment because of irAEs, 73% were aged 65 years or older.
  • Patients with only low-grade toxicities were significantly less likely to be hospitalized than those with high-grade toxicities (15% vs 61%, P < .001).

IN PRACTICE:

“The burden of low-grade toxicity is clinically significant in patients treated with adjuvant pembrolizumab for stage III melanoma with associated treatment discontinuation and need for immunosuppressive treatment for irAEs. This is particularly notable in the older population,” the authors wrote. “Both low-grade and high-grade toxicities should be considered in the risk-benefit assessment, and holistic support for irAEs across all toxicity grades should be integral to the management paradigm,” they added.

SOURCE:

The study, led by Nasreen Abdul Aziz, MBBCh, Belfast City Hospital, Belfast Health and Social Care Trust, Belfast, Northern Ireland, was published online in JCO Oncology Practice.

LIMITATIONS:

The retrospective study design and reliance on hospital records led to difficulty in determining whether symptoms were treatment-related or attributable to other conditions or therapies. Additionally, grading toxicity from medical records may have led to the underreporting of some low-grade toxicities. The BRAF mutation rate was low in the cohort, likely due to the availability of alternative adjuvant BRAF/MEK inhibitors during the study period.

DISCLOSURES:

No funding details were reported by the authors. One author disclosed receiving honoraria from DePuy companies and having other ties with various organizations. Another author reported having a consulting or advisory role with Bristol Myers Squibb UK.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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