A phase two study of high dose blinatumomab in Richter’s syndrome

Philip A. Thompson, Xianli Jiang, Pinaki Banerjee, Rafet Basar, Naveen Garg, Ken Chen, Mecit Kaplan, Vandana Nandivada, Ana Karen Nunez Cortes, Alessandra Ferrajoli, Michael J. Keating, Christine B. Peterson, Michael Andreeff, Katayoun Rezvani, William G. Wierda

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Richter’s Syndrome (RS) is an aggressive transformation of CLL, usually clonally-related diffuse large B-cell lymphoma (DLBCL), characterized by frequent TP53 mutations, intrinsic chemoresistance and poor survival. TP53-independent treatments are needed. We conducted a single center, phase 2, investigator-initiated study of high dose blinatumomab (maximum 112 mcg/d after initial, weekly dose escalation), NCT03121534, given for an 8-week induction and 4-week consolidation cycle. Responses were assessed by Lugano 2014 criteria. Serial multi-parameter flow cytometry from blood was performed to identify patient-specific biomarkers for response. Nine patients were treated. Patients had received a median of 4 and 2 prior therapies for CLL and RS, respectively. Five of 9 had del(17p) and 100% had complex karyotype. Four patients had reduction in nodal disease, including one durable complete response lasting >1 y. Treatment was well tolerated, with no grade >3 cytokine release syndrome and 1 case of grade 3, reversible neurotoxicity. Immunophenotyping demonstrated the majority of patients expressed multiple immune checkpoints, especially PD1, TIM3 and TIGIT. The patient who achieved CR had the lowest levels of immune checkpoint expression. Simultaneous targeting with immune checkpoint blockade, especially PD1 inhibition, which has already demonstrated single-agent efficacy in RS, could achieve synergistic killing and enhance outcomes.

Original languageEnglish (US)
Pages (from-to)2228-2232
Number of pages5
Issue number9
StatePublished - Sep 2022

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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