Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy

A report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project

Kenneth R. Carson, Scott D. Newsome, Ellen J. Kim, Nina D. Wagner-Johnston, Gloria Von Geldern, Craig Moskowitz, Alison J. Moskowitz, Alain H. Rook, Pankaj Jalan, Alison W. Loren, Daniel Landsburg, Thomas Coyne, Donald Tsai, Dennis W. Raisch, Leann B. Norris, P. Brandon Bookstaver, Oliver Sartor, Charles L. Bennett

Research output: Contribution to journalArticle

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Abstract

BACKGROUND Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody-drug conjugate that was approved in 2011 for the treatment of patients with anaplastic large cell and Hodgkin lymphomas. The product label indicates that 3 patients who were treated with BV developed progressive multifocal leukoencephalopathy (PML), a frequently fatal JC virus-induced central nervous system infection. Prior immunosuppressive therapy and compromised immune systems were postulated risk factors. In the current study, the authors reported 5 patients who developed BV-associated PML, including 2 immunocompetent patients. METHODS Case information was obtained from clinicians (4 patients) or a US Food and Drug Administration database (1 patient). RESULTS All 5 patients had lymphoid malignancies. Two patients with cutaneous T-cell lymphomas had not previously received chemotherapy. PML developed after a median of 3 BV doses (range, 2 doses-6 doses) and within a median of 7 weeks after BV initiation (range, 3 weeks-34 weeks). Presenting findings included aphasia, dysarthria, confusion, hemiparesis, and gait dysfunction; JC virus in the cerebrospinal fluid (2 patients) or central nervous system biopsy (3 patients); and brain magnetic resonance imaging scans with white matter abnormalities (5 patients). Four patients died at a median of 8 weeks (range, 6 weeks-16 weeks) after PML diagnosis. The sole survivor developed immune reconstitution inflammatory syndrome. CONCLUSIONS PML can develop after a few BV doses and within weeks of BV initiation. Clinicians should be aware of this syndrome, particularly when neurologic changes develop after the initiation of BV treatment. The decision to administer BV to patients with indolent cutaneous lymphomas should be based on consideration of risk-benefit profiles and of alternative options.

Original languageEnglish (US)
Pages (from-to)2464-2471
Number of pages8
JournalCancer
Volume120
Issue number16
DOIs
StatePublished - Aug 15 2014
Externally publishedYes

Fingerprint

Progressive Multifocal Leukoencephalopathy
Therapeutics
JC Virus
cAC10-vcMMAE
Immune Reconstitution Inflammatory Syndrome
Pharmaceutical Databases
Anaplastic Large-Cell Lymphoma
Cutaneous T-Cell Lymphoma
Central Nervous System Infections
Dysarthria
Aphasia
Paresis
Immunosuppressive Agents
Hodgkin Disease
Gait
Nervous System

Keywords

  • autoimmune
  • brentuximab
  • fungoides
  • immunocompromised
  • lymphoma
  • vedotin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy : A report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project. / Carson, Kenneth R.; Newsome, Scott D.; Kim, Ellen J.; Wagner-Johnston, Nina D.; Von Geldern, Gloria; Moskowitz, Craig; Moskowitz, Alison J.; Rook, Alain H.; Jalan, Pankaj; Loren, Alison W.; Landsburg, Daniel; Coyne, Thomas; Tsai, Donald; Raisch, Dennis W.; Norris, Leann B.; Bookstaver, P. Brandon; Sartor, Oliver; Bennett, Charles L.

In: Cancer, Vol. 120, No. 16, 15.08.2014, p. 2464-2471.

Research output: Contribution to journalArticle

Carson, KR, Newsome, SD, Kim, EJ, Wagner-Johnston, ND, Von Geldern, G, Moskowitz, C, Moskowitz, AJ, Rook, AH, Jalan, P, Loren, AW, Landsburg, D, Coyne, T, Tsai, D, Raisch, DW, Norris, LB, Bookstaver, PB, Sartor, O & Bennett, CL 2014, 'Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: A report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project', Cancer, vol. 120, no. 16, pp. 2464-2471. https://doi.org/10.1002/cncr.28712
Carson, Kenneth R. ; Newsome, Scott D. ; Kim, Ellen J. ; Wagner-Johnston, Nina D. ; Von Geldern, Gloria ; Moskowitz, Craig ; Moskowitz, Alison J. ; Rook, Alain H. ; Jalan, Pankaj ; Loren, Alison W. ; Landsburg, Daniel ; Coyne, Thomas ; Tsai, Donald ; Raisch, Dennis W. ; Norris, Leann B. ; Bookstaver, P. Brandon ; Sartor, Oliver ; Bennett, Charles L. / Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy : A report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project. In: Cancer. 2014 ; Vol. 120, No. 16. pp. 2464-2471.
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abstract = "BACKGROUND Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody-drug conjugate that was approved in 2011 for the treatment of patients with anaplastic large cell and Hodgkin lymphomas. The product label indicates that 3 patients who were treated with BV developed progressive multifocal leukoencephalopathy (PML), a frequently fatal JC virus-induced central nervous system infection. Prior immunosuppressive therapy and compromised immune systems were postulated risk factors. In the current study, the authors reported 5 patients who developed BV-associated PML, including 2 immunocompetent patients. METHODS Case information was obtained from clinicians (4 patients) or a US Food and Drug Administration database (1 patient). RESULTS All 5 patients had lymphoid malignancies. Two patients with cutaneous T-cell lymphomas had not previously received chemotherapy. PML developed after a median of 3 BV doses (range, 2 doses-6 doses) and within a median of 7 weeks after BV initiation (range, 3 weeks-34 weeks). Presenting findings included aphasia, dysarthria, confusion, hemiparesis, and gait dysfunction; JC virus in the cerebrospinal fluid (2 patients) or central nervous system biopsy (3 patients); and brain magnetic resonance imaging scans with white matter abnormalities (5 patients). Four patients died at a median of 8 weeks (range, 6 weeks-16 weeks) after PML diagnosis. The sole survivor developed immune reconstitution inflammatory syndrome. CONCLUSIONS PML can develop after a few BV doses and within weeks of BV initiation. Clinicians should be aware of this syndrome, particularly when neurologic changes develop after the initiation of BV treatment. The decision to administer BV to patients with indolent cutaneous lymphomas should be based on consideration of risk-benefit profiles and of alternative options.",
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T2 - A report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project

AU - Carson, Kenneth R.

AU - Newsome, Scott D.

AU - Kim, Ellen J.

AU - Wagner-Johnston, Nina D.

AU - Von Geldern, Gloria

AU - Moskowitz, Craig

AU - Moskowitz, Alison J.

AU - Rook, Alain H.

AU - Jalan, Pankaj

AU - Loren, Alison W.

AU - Landsburg, Daniel

AU - Coyne, Thomas

AU - Tsai, Donald

AU - Raisch, Dennis W.

AU - Norris, Leann B.

AU - Bookstaver, P. Brandon

AU - Sartor, Oliver

AU - Bennett, Charles L.

PY - 2014/8/15

Y1 - 2014/8/15

N2 - BACKGROUND Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody-drug conjugate that was approved in 2011 for the treatment of patients with anaplastic large cell and Hodgkin lymphomas. The product label indicates that 3 patients who were treated with BV developed progressive multifocal leukoencephalopathy (PML), a frequently fatal JC virus-induced central nervous system infection. Prior immunosuppressive therapy and compromised immune systems were postulated risk factors. In the current study, the authors reported 5 patients who developed BV-associated PML, including 2 immunocompetent patients. METHODS Case information was obtained from clinicians (4 patients) or a US Food and Drug Administration database (1 patient). RESULTS All 5 patients had lymphoid malignancies. Two patients with cutaneous T-cell lymphomas had not previously received chemotherapy. PML developed after a median of 3 BV doses (range, 2 doses-6 doses) and within a median of 7 weeks after BV initiation (range, 3 weeks-34 weeks). Presenting findings included aphasia, dysarthria, confusion, hemiparesis, and gait dysfunction; JC virus in the cerebrospinal fluid (2 patients) or central nervous system biopsy (3 patients); and brain magnetic resonance imaging scans with white matter abnormalities (5 patients). Four patients died at a median of 8 weeks (range, 6 weeks-16 weeks) after PML diagnosis. The sole survivor developed immune reconstitution inflammatory syndrome. CONCLUSIONS PML can develop after a few BV doses and within weeks of BV initiation. Clinicians should be aware of this syndrome, particularly when neurologic changes develop after the initiation of BV treatment. The decision to administer BV to patients with indolent cutaneous lymphomas should be based on consideration of risk-benefit profiles and of alternative options.

AB - BACKGROUND Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody-drug conjugate that was approved in 2011 for the treatment of patients with anaplastic large cell and Hodgkin lymphomas. The product label indicates that 3 patients who were treated with BV developed progressive multifocal leukoencephalopathy (PML), a frequently fatal JC virus-induced central nervous system infection. Prior immunosuppressive therapy and compromised immune systems were postulated risk factors. In the current study, the authors reported 5 patients who developed BV-associated PML, including 2 immunocompetent patients. METHODS Case information was obtained from clinicians (4 patients) or a US Food and Drug Administration database (1 patient). RESULTS All 5 patients had lymphoid malignancies. Two patients with cutaneous T-cell lymphomas had not previously received chemotherapy. PML developed after a median of 3 BV doses (range, 2 doses-6 doses) and within a median of 7 weeks after BV initiation (range, 3 weeks-34 weeks). Presenting findings included aphasia, dysarthria, confusion, hemiparesis, and gait dysfunction; JC virus in the cerebrospinal fluid (2 patients) or central nervous system biopsy (3 patients); and brain magnetic resonance imaging scans with white matter abnormalities (5 patients). Four patients died at a median of 8 weeks (range, 6 weeks-16 weeks) after PML diagnosis. The sole survivor developed immune reconstitution inflammatory syndrome. CONCLUSIONS PML can develop after a few BV doses and within weeks of BV initiation. Clinicians should be aware of this syndrome, particularly when neurologic changes develop after the initiation of BV treatment. The decision to administer BV to patients with indolent cutaneous lymphomas should be based on consideration of risk-benefit profiles and of alternative options.

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