27P - Nivolumab immunotherapy in malignant mesothelioma

Date 05 November 2016
Event ESMO Symposium on Immuno-Oncology 2016
Session Lunch and general poster viewing
Presenter Milan Bhandari
Citation Annals of Oncology (2016) 27 (suppl_8): viii4-viii17. 10.1093/annonc/mdw527
Authors M. Bhandari1, A.S. Dugar2
  • 1Hematology Oncology, The Christ Hospital, 45242 - Cincinnati/US
  • 2Dept Of Biology, Wellesley College, 02481 - Boston/US

Abstract

Aim/Background

Malignant pleural mesothelioma (MPM) is a highly lethal cancer with an overall survival of ∼12 months even with aggressive intervention. Frontline systemic therapy with cisplatin and pemetrexed has a response rate of ∼35-41%; currently, there are no FDA approved second line therapies for MPM. Immune checkpoint blockade is a new treatment modality with promising outcomes in several forms of cancer and have shown promise in murine invitro studies with MPM. Herein, we investigate a case series of 3 patients with metastatic malignant mesothelioma (stage IV) who experienced disease progression on standard therapy but had an exceptional response to immune checkpoint inhibition with nivolumab (Opdivo ®, Bristol-Myers Squibb).

Methods

Institution approved compassionate access program guided therapy utilizing Nivolumab (Opdivo) at 3mg/kg dose every 2 weeks as continuous therapy till disease progression or unacceptable toxicity.

Results

We report a case series of 3 patients treated on a compassionate access single institution protocol upon disease progression post frontline cisplatin and pemetrexed. One patient obtained very rapid and marked clinical benefit within 6 weeks of start of nivolumab therapy and complete clinical and radiographic remission at 6 months of treatment; is alive with an ECOG PS 0 at 12 months. Another two patients have stable disease lasting over 8 months, resolution of pleural effusion and with improvement in performance status from ECOG 2 to ECOG 1 and continue therapy utilizing nivolumab as second line therapy. Rather than IHC staining for PD-1 or PDL-1, assessment of tumor mutation burden (TMB) has been predictive of response to checkpoint inhibition utilizing nivolumab in these 3 patients. Overall response rate in this small case series is 100% and time of progression over 8 months, which is unprecedented as second line therapy for malignant mesothelioma.

Conclusions

Checkpoint inhibitors may have a large role to play in salvage second line therapy for metastatic mesothelioma and a new era of investigation utilizing immunotherapy for metastatic mesothelioma is beginning with much anticipation. Tumor mutation burden (TMB) has been found to be more predictive of clinical response, rather than IHC for PD-1 or PDL-1 in our small single institution case series.

Clinical trial identification

NA

Legal entity responsible for the study

The Christ Hospital, Cincinnati, Ohio

Funding

The Christ Hospital, Cincinnati, Ohio

Disclosure

All authors have declared no conflicts of interest.