Sequential immunotherapy in a patient with primary refractory Hodgkin lymphoma and novel mutations

Oncotarget
Richard GreilSigrun Greil-Ressler

Abstract

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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Citations

Oct 5, 2019·Journal of Clinical Medicine·Valli De ReMaurizio Mascarin
Dec 16, 2019·European Journal of Haematology·Sandro M WagnerChristian Sillaber

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Methods Mentioned

BETA
biopsy
biopsies
BRIP
PCR

Clinical Trials Mentioned

NCT00576654
NCT01742988
NCT01991938
NCT02431260
NCT01943851
NCT01949883

Software Mentioned

FoundationOne

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