Inclusion of Rituximab in Treatment Protocols for Non-Hodgkin's Lymphomas and Risk for Progressive Multifocal Leukoencephalopathy

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BlankThe Oncologist, Vol. 15, No. 11, 1214-1219, November 2010;

doi:10.1634/theoncologist.2010-0098

Inclusion of Rituximab in Treatment Protocols for Non-Hodgkin's Lymphomas and

Risk for Progressive Multifocal Leukoencephalopathy

Marco Tuccoria,d, e Focosib, Corrado Blandizzia,d, Matteo Pelosinib,

Montagnania,d, Fabrizio Maggic, Mauro Pistelloc, Luca lia, Matteo

Fornaia, Pasquale Pepee, Giuseppe Rossie, Petrinib

aDivision of Pharmacology and Chemotherapy, Department of Internal Medicine,

bDivision of Haematology, Department of Oncology, Transplantations and New

Technologies in Medicine, and cVirology Section and Retrovirus Centre,

Department of Experimental Pathology, University of Pisa, Pisa, Italy; dTuscan

Regional Centre of Pharmacovigilance, Pisa, Italy; eInstitute of Clinical

Physiology, Unit of Epidemiology and Biostatistics, National Research Council,

Pisa, Italy

Correspondence: e Focosi, M.D., Ph.D., via Roma 56, 56126, Pisa, Italy.

Telephone: 39-050-995486; Fax: 39-050-8312268; e-mail: dfocosi@...

Received April 6, 2010; accepted for publication October 5, 2010; first

published online in THE ONCOLOGIST Express on November 1, 2010.

Disclosures

Marco Tuccori: None; e Focosi: None; Corrado Blandizzi: None; Matteo

Pelosini: None; Montagnani: None; Fabrizio Maggi: None; Mauro Pistello:

None; Luca li: None; Matteo Fornai: None; Pasquale Pepe: None; Giuseppe

Rossi: None; Petrini: None.

Section Editor Canellos discloses that he serves as a consultant for the

Celgene Business Advisory Board.

Reviewer " A " discloses no financial relationships.

Reviewer " B " discloses no financial relationships.

Reviewer " C " serves on a speakers bureau for Genentech.

The content of this article has been reviewed by independent peer reviewers to

ensure that it is balanced, objective, and free from commercial bias. On the

basis of disclosed information, all conflicts of interest have been resolved.

Objectives. Rituximab is an anti-CD20 monoclonal antibody that promotes better

treatment outcomes in patients with non-Hodgkin's lymphoma (NHL). Case series of

progressive multifocal leukoencephalopathy (PML) in patients receiving rituximab

within polychemotherapy regimens have led to the introduction of a black box

warning, but no risk estimation has ever been provided.

Methods. We performed a retrospective, monocentric cohort study on 976 NHL

patients diagnosed in 1994–2008, including 517 patients who received at least

one dose of rituximab.

Results. Inclusion of rituximab into standard chemotherapy regimens for NHL

caused a significantly higher incidence of PML cases (rate difference, 2.2 every

1,000 patient-years; 95% confidence interval, 0.1–4.3).

Interpretation. Based on this finding, clinical surveillance of PML-related

symptoms is recommended in NHL patients exposed to rituximab.