Phase I study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreo-retinal lymphoma

Han W. Tun, Patrick B. Johnston, Lisa M. DeAngelis, Pamela J. Atherton, Levi D. Pederson, Patricia A. Koenig, Craig B. Reeder, Antonio M. Padula Omuro, David Schiff, Brian O'Neill, Jose Pulido, Kurt A. Jaeckle, Christian Grommes and Thomas E. Witzig

Key points

  • Maximal tolerated dose of pomalidomide for relapsed/refractory PCNSL is 5 mg PO daily for 21 days every 28 days.

  • Pomalidomide and dexamethasone combination has therapeutic activity against relapsed/refractory PCNSL.


The combination of pomalidomide (POM) and dexamethasone (DEX) was evaluated for relapsed/refractory primary CNS lymphoma (PCNSL) and primary vitreo-retinal lymphoma (PVRL) to determine the maximal tolerated dose (MTD) of POM as the primary objective, and overall response rate (ORR), progression-free survival (PFS), and safety profile as the secondary objectives. Cohorts-of-three study design was used with dose escalation schedule consisting of POM (3 mg, 5 mg, 7 mg, or 10 mg) PO daily for 21 days every 28 days and DEX 40 mg PO every week (#NCT01722305, After 2 cycles, POM was continued alone until disease progression, intolerance, or subject withdrawal. Following MTD determination, MTD cohort was expanded. 25/29 patients with the median of 3 prior treatments were eligible for assessment as per international PCNSL collaborative group criteria. The MTD of POM was 5 mg daily for 21 days every 28 days. ORR (whole study) was 48% (12/25; 95% CI- 27.8%, 68.7%) with 6 CR (complete response), 2 CRu (complete response, unconfirmed) and 4 PR (partial response). ORR (MTD cohort) was 50% (8/16; 95% CI- 24.7%, 75.4%) with 5 CR, 1 CRu and 2 PR. Median PFS was 5.3 months (whole study) and 9 months (for responders). One patient had pseudo-progression. Grade 3/4 hematologic toxicities included neutropenia (21%), anemia (8%), and thrombocytopenia (8%). Grade 3/4 non-hematologic toxicities included lung infection (12%), sepsis (4%), fatigue (8%), syncope (4%), dyspnea (4%), hypoxia (4%), respiratory failure (8%), and rash (4%). POM/DEX treatment is feasible with significant therapeutic activity against relapsed/refractory PCNSL and PVRL. The study is registered to as NCT01722305.

  • Submitted February 23, 2018.
  • Accepted September 19, 2018.