Scientific Publications and Presentations

Fibrolamellar carcinoma transcriptomic-based treatment prediction: complete response after nivolumab and ipilimumab

December 9, 2022

Berger, Dinstag, Tirosh, Schiff, Kleiner, Aldape, Ruppin, Beker, Kurzrock
Journal article in Journal for ImmunoTherapy of Cancer

This paper discusses a case study of a patient in her mid 30s whose FLC had recurred and persisted despite resection and multiple lines of treatment, including use of an immune checkpoint inhibitor (atezolizumab – an anti-PD-L1 agent). Following molecular profiling of her tumor and computational analysis of the tumor’s transcriptome (RNA), a combination of two immune checkpoint inhibitors – ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) – was prescribed. That treatment led to complete remission of her cancer, despite factors that generally indicate that an immune checkpoint blockade may not be successful:

  1. a low level of random mutations (low tumor mutational burden), and
  2. the absence of expression of PD-L-1 and the prior failure of the patient to respond to an anti-PD-L1 checkpoint inhibitor (atezolizumab).

As of the time of the paper’s publication, the patient was still in remission.

While this study describes the experience of only one patient, it illustrates the potential power of precision medicine – the use molecular and advanced computational analysis of a patient’s specific tumor to guide patient-specific treatment approaches. In addition, this case study illustrates that a patient’s prior failure to respond to a single ICI and/or the lack of PD-L1 expression by the FLC cells, do not necessarily preclude an excellent response to dual immune checkpoint blockade targeting both the PD-1 and CTLA-4 systems.

The molecular analysis driving this case study was conducted by Pangea Biomed (, a computational precision oncology company. The company’s ‘ENLIGHT’ engine analyzed gene expression patterns in the patient’s tumor’s RNAseq, to predict the tumor’s response to a wide array of targeted and immuno-oncology therapies. Using “big data”, the ‘ENLIGHT’ engine assigned scores to different drugs denoting the predicted likelihood that this patient would respond to the drugs. Drugs with higher scores, including the dual checkpoint inhibitor combination in this study, were highlighted for consideration by the patient’s clinical team.

The complete case report can be read here.

Note: Corresponding author Razelle Kurzrock, MD is a member of FCF’s Medical & Scientific Advisory Board. She gave a keynote presentation discussing this case at the Fibrolamellar Scientific Summit that FCF hosted in April 2023. That keynote can be viewed on FCF’s YouTube channel. Other key authors, including Raanan Berger, Eytan Ruppin, and Tuvik Beker participated in the 2023 conference as well.

Mark Furth, FCF’s Scientific Director, helped with manuscript development.

If interested in learning more about the promise of precision medicine, please see FCF’s YouTube channel to watch the “Precision Medicine for Rare Cancer” series – both Razelle Kurzrock and Eytan Ruppin served as panelists during that series.