Sequential immunotherapy in a patient with primary refractory Hodgkin lymphoma and novel mutations
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Richard Greil1,2,3, Lisa Pleyer1,2,3, Bettina Jansko1, Carmen Feierabend1, Lukas Rettenbacher4, Olga Stiefel5, Christoph Rass1, Patrick Morre1, Daniel Neureiter3,6 and Sigrun Greil-Ressler1
1IIIrd Medical Department with Hematology, Medical Oncology, Hemostaseology, Infectious Disease and Rheumatology, Oncologic Center, Paracelsus Medical University, A-5020 Salzburg, Austria
2Salzburg Cancer Research Institute, A-5020 Salzburg, Austria
3Cancer Cluster Salzburg, A-5020 Salzburg, Austria
4Department of Nuclear Medicine, Paracelsus Medical University, A-5020 Salzburg, Austria
5Ordensklinikum Linz, A-4010 Linz, Austria
6Institute of Pathology, Paracelsus Medical University, A-5020 Salzburg, Austria
Richard Greil, email: firstname.lastname@example.org
Keywords: immunotherapy; molecular targets; gene mutations; lymphoma
Received: April 12, 2017 Accepted: March 15, 2018 Published: April 17, 2018
Primary resistant Hodgkin lymphoma is an aggressive disease with few treatment options and short survival. Neoplastic cells of classical Hodgkin lymphoma are heavily dependent on microenvironmental stimuli, regularly express PD-L1, and a relevant proportion of relapsed patients is sensitive to blocking of the PD1/PD-L1 axis. However, response duration is limited and further treatment options are unknown but urgently needed.
We report a case of a patient without relevant response to five subsequent chemotherapy regimens who immediately and dramatically responded to an anti-PD1 mab. During the following two years she responded to the anti-CTLA-4 mab ipilimumab, the Jak2 inhibitor ruxolitinib, and a combination of lenalidomide plus cyclophosphamide given in subsequent relapses. A thorough genomic analysis demonstrated seven genomic alterations with six of them not previously described in this disease (i.e. BRIP1 G212fs*62, KRAS L19F, KDM5A R1239W, MYC A59T, ARIDA1A E1683fs*15 and TP53 277Y). Three alterations were considered actionable and one of them drugable. The number of mutations increased over time and the BRIP1 mutation was found to be a germline mutation.
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