Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal 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 Jaeckle, Christian Grommes, Thomas E. Witzig

Research output: Contribution to journalArticle

4 Citations (Scopus)

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) ofPOMas 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 doseescalation 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.

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
Anemia
Sepsis
Appointments and Schedules

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Tun, H. W., Johnston, P. B., DeAngelis, L. M., Atherton, P. J., Pederson, L. D., Koenig, P. A., ... Witzig, T. E. (2018). Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma. Blood, 132(21), 2240-2248. https://doi.org/10.1182/blood-2018-02-835496
Tun, Han W. ; Johnston, Patrick B. ; DeAngelis, Lisa M. ; Atherton, Pamela J. ; Pederson, Levi D. ; Koenig, Patricia A. ; Reeder, Craig B. ; Padula Omuro, Antonio M. ; Schiff, David ; O'Neill, Brian ; Pulido, Jose ; Jaeckle, Kurt ; Grommes, Christian ; Witzig, Thomas E. / 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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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) ofPOMas 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 doseescalation 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.",
author = "Tun, {Han W.} and Johnston, {Patrick B.} and DeAngelis, {Lisa M.} and Atherton, {Pamela J.} and Pederson, {Levi D.} and Koenig, {Patricia A.} and Reeder, {Craig B.} and {Padula Omuro}, {Antonio M.} and David Schiff and Brian O'Neill and Jose Pulido and Kurt Jaeckle and Christian Grommes and Witzig, {Thomas E.}",
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Tun, HW, Johnston, PB, DeAngelis, LM, Atherton, PJ, Pederson, LD, Koenig, PA, Reeder, CB, Padula Omuro, AM, Schiff, D, O'Neill, B, Pulido, J, Jaeckle, K, 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

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

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

Research output: Contribution to journalArticle

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T1 - Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma

AU - Tun, Han W.

AU - Johnston, Patrick B.

AU - DeAngelis, Lisa M.

AU - Atherton, Pamela J.

AU - Pederson, Levi D.

AU - Koenig, Patricia A.

AU - Reeder, Craig B.

AU - Padula Omuro, Antonio M.

AU - Schiff, David

AU - O'Neill, Brian

AU - Pulido, Jose

AU - Jaeckle, Kurt

AU - Grommes, Christian

AU - Witzig, Thomas E.

PY - 2018/11/22

Y1 - 2018/11/22

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) ofPOMas 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 doseescalation 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.

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Tun HW, Johnston PB, DeAngelis LM, Atherton PJ, Pederson LD, Koenig PA et al. Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma. Blood. 2018 Nov 22;132(21):2240-2248. https://doi.org/10.1182/blood-2018-02-835496