Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma

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

Research output: Contribution to journalArticle

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Abstract

The combination of pomalidomide (POM) and dexamethasone (DEX) was evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL) and primary vitreoretinal 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 secondary objectives. A cohorts-of-3 study design was used with a dose-escalation schedule consisting of POM (3, 5, 7, or 10 mg) orally daily for 21 days every 28 days and DEX 40 mg orally every week. After 2 cycles, POM was continued alone until disease progression, intolerance, or subject withdrawal. Following MTD determination, the MTD cohort was expanded. Twenty-five of 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. Whole-study ORR was 48% (12 of 25; 95% confidence interval [CI], 27.8%, 68.7%) with 6 complete response (CR), 2 complete response, unconfirmed (CRu), and 4 partial response (PR). MTD cohort ORR was 50% (8 of 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 pseudoprogression. Grade 3/4 hematologic toxicities included neutropenia (21%), anemia (8%), and thrombocytopenia (8%). Grade 3/4 nonhematologic 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. This trial was registered at www.clinicaltrials.gov as #NCT01722305.

Original languageEnglish (US)
Pages (from-to)2240-2248
Number of pages9
JournalBlood
Volume132
Issue number21
DOIs
StatePublished - Nov 22 2018

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Maximum Tolerated Dose
Refractory materials
Dexamethasone
Lymphoma
Neurology
Central Nervous System
Disease-Free Survival
Toxicity
Confidence Intervals
Syncope
Exanthema
Neutropenia
Respiratory Insufficiency
Thrombocytopenia
Dyspnea
Fatigue
Disease Progression
pomalidomide
Anemia
Sepsis

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma. / Tun, Han W; Johnston, Patrick Bruce; DeAngelis, Lisa M.; Atherton, Pamela J.; Pederson, Levi D.; Koenig, Patricia A.; Reeder, Craig B.; Omuro, Antonio M.Padula; Schiff, David; O'Neill, Brian Patrick; Pulido, Jose S; Jaeckle, Kurt A.; Grommes, Christian; Witzig, Thomas Elmer.

In: Blood, Vol. 132, No. 21, 22.11.2018, p. 2240-2248.

Research output: Contribution to journalArticle

Tun, HW, Johnston, PB, DeAngelis, LM, Atherton, PJ, Pederson, LD, Koenig, PA, Reeder, CB, Omuro, AMP, Schiff, D, O'Neill, BP, Pulido, JS, Jaeckle, KA, Grommes, C & Witzig, TE 2018, 'Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma', Blood, vol. 132, no. 21, pp. 2240-2248. https://doi.org/10.1182/blood-2018-02-835496
Tun, Han W ; Johnston, Patrick Bruce ; DeAngelis, Lisa M. ; Atherton, Pamela J. ; Pederson, Levi D. ; Koenig, Patricia A. ; Reeder, Craig B. ; Omuro, Antonio M.Padula ; Schiff, David ; O'Neill, Brian Patrick ; Pulido, Jose S ; Jaeckle, Kurt A. ; Grommes, Christian ; Witzig, Thomas Elmer. / Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma. In: Blood. 2018 ; Vol. 132, No. 21. pp. 2240-2248.
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AU - Johnston, Patrick Bruce

AU - DeAngelis, Lisa M.

AU - Atherton, Pamela J.

AU - Pederson, Levi D.

AU - Koenig, Patricia A.

AU - Reeder, Craig B.

AU - Omuro, Antonio M.Padula

AU - Schiff, David

AU - O'Neill, Brian Patrick

AU - Pulido, Jose S

AU - Jaeckle, Kurt A.

AU - Grommes, Christian

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N2 - The combination of pomalidomide (POM) and dexamethasone (DEX) was evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL) and primary vitreoretinal 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 secondary objectives. A cohorts-of-3 study design was used with a dose-escalation schedule consisting of POM (3, 5, 7, or 10 mg) orally daily for 21 days every 28 days and DEX 40 mg orally every week. After 2 cycles, POM was continued alone until disease progression, intolerance, or subject withdrawal. Following MTD determination, the MTD cohort was expanded. Twenty-five of 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. Whole-study ORR was 48% (12 of 25; 95% confidence interval [CI], 27.8%, 68.7%) with 6 complete response (CR), 2 complete response, unconfirmed (CRu), and 4 partial response (PR). MTD cohort ORR was 50% (8 of 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 pseudoprogression. Grade 3/4 hematologic toxicities included neutropenia (21%), anemia (8%), and thrombocytopenia (8%). Grade 3/4 nonhematologic 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. This trial was registered at www.clinicaltrials.gov as #NCT01722305.

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