Highlights
- •Despite high response rates with combination immunotherapy, many later progress.
- •Aside from BRAF/MEKi, there are no standard subsequent therapies available.
- •The role of reinduction with ipilimumab (alone or in combination) is unclear.
- •The response rate to reinduction was 26%, and the disease control rate was 45%.
- •38% had grade 3/4 toxicity, but only 40% of induction toxicities recurred.
Abstract
Purpose
Combination immunotherapy with nivolumab and ipilimumab has a high initial response
rate in advanced melanoma; however, up to 55% of patients later progress. The efficacy
and safety of ipilimumab re-induction in the setting of acquired resistance (AR) to
combination immunotherapy is unknown.
Methods
Patients with advanced melanoma who initially achieved a complete response, partial
response or sustained stable disease to induction combination immunotherapy then progressed
and were reinduced with ipilimumab (alone or in combination with anti–PD-1) and were
analysed retrospectively. Demographics, disease characteristics, efficacy and toxicity
were examined.
Results
Forty-seven patients were identified from 12 centres. The response rate to reinduction
therapy was 12/47 (26%), and disease control rate was 21/47 (45%). Responses appeared
more frequent in patients who developed AR after ceasing induction immunotherapy (30%
vs. 18%, P = 0.655). Time to AR was 11 months (95% confidence interval [CI], 8–15
months). After a median follow-up of 16 months (95% CI, 10–25 months), responders
to reinduction had a median progression-free survival of 14 months (95% CI, 13, NR
months), and in the whole cohort, the median overall survival from reinduction was
17 months (95% CI, 12–NR months). Twenty-seven (58%) immune-related adverse events
(irAEs) were reported; 18 (38%) were grade 3/4, and in 11 of 27 (40%), the same irAE
observed during induction therapy recurred.
Conclusions
Reinduction with ipilimumab ± anti–PD-1 has modest clinical activity. Clinicians should
be attentive to the risk of irAEs, including recurrence of irAEs that occurred during
induction therapy. Future studies are necessary to determine best management after
resistance to combination immunotherapy.
Keywords
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Article info
Publication history
Published online: June 29, 2021
Accepted:
April 16,
2021
Received in revised form:
March 24,
2021
Received:
December 11,
2020
Footnotes
This study was presented in part at the European Society of Medical Oncology Congress 2019 in Barcelona.
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
