Novel Treatment Approach Shows Promise for Patients with Operable Mesothelioma

Strategic Insights -

A new study has shown promise for a novel treatment approach using combination immunotherapy before and after surgery for patients with operable mesothelioma, a rare and aggressive cancer typically caused by asbestos exposure. The study, led by investigators at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy, found that preoperative (neoadjuvant) nivolumab, alone or in combination with ipilimumab, followed by surgery and postoperative nivolumab, was feasible and safe, with manageable side effects, and showed encouraging survival outcomes.

Key Takeaways:

  • The study is the first to test perioperative (pre- and post-surgery) combination immune checkpoint blockade in mesothelioma and the first to pair it with ultra-sensitive liquid biopsy analyses to detect residual disease and link circulating tumor DNA (ctDNA) with clinical outcomes.
  • Over 80% of patients successfully underwent surgery within the preplanned window after receiving neoadjuvant immunotherapy.
  • Patients treated with the combination regimen (nivolumab and ipilimumab) lived a median of 28.6 months, with nearly 36% alive and recurrence-free at follow-up.
  • Average survival for mesothelioma is 18 months.
  • The study found that patients who had undetectable ctDNA levels after neoadjuvant immunotherapy and before surgery, or who showed a 95% or greater drop in ctDNA during treatment, experienced significantly longer event-free and overall survival.
  • Persistent ctDNA was linked with early disease progression, even when imaging results appeared stable.

Statistics:

  • 80% of patients successfully underwent surgery within the preplanned window after receiving neoadjuvant immunotherapy.
  • 36% of patients were alive and recurrence-free at follow-up after treatment with the combination regimen.
  • 28.6 months was the median survival time for patients treated with the combination regimen.
  • 18 months is the average survival time for mesothelioma.

Sources:

  • Johns Hopkins Medicine
  • Nature Medicine
  • Department of Defense Congressionally Directed Medical Research Programs grant CA190755
  • Johns Hopkins Kimmel Cancer Center NCI Support Grant NCI CCSG P30 CA006973
  • U.S. Food and Drug Administration grant U01FD005942-FDA
  • National Institutes of Health grant CA1211113
  • Bloomberg~Kimmel Institute for Cancer Immunotherapy
  • ECOG-ACRIN Thoracic Malignancies Integrated Translational Science Center Grant UG1CA233259
  • Robyn Adler Fellowship Award
  • Commonwealth Foundation
  • Mark Foundation for Cancer Research
  • Florence Lomax Eley Fund