29th European Congress of Pathology

Malignancies in patients with ANCA-associated vasculitis

Chinar Rahmattulla

06-09-2017

ANCA-associated vasculitis (AAV)

Systemic autoimmune disease

• Granulomatosis with polyangiitis (GPA)

• Microscopic polyangiitis (MPA)

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ANCAs

• ANCA = Anti-Neutrophil Cytoplasmic Autoantibody

• Directed against components in the primary granules of the neutrophil

• GPA – usually proteinase 3 (PR3)-ANCA

• MPA – usually myeloperoxidase (MPO)–ANCA

Presentation of ANCA associated vasculitis

Berden,

BMJ 2012

Prognosis

• Life-threatening when untreated

• 1-year mortality: 80%

• Immunosuppressive therapy has dramatically improved prognosis

• 1-year remission rate: 90%

• Therapy regimen

• Induction therapy: cyclophosphamide + prednisone

• Remission therapy: azathioprine / mycophenolate mofetil (MMF)

Malignancy risk in AAV

• Better prognosis attention shifted to long-term complications

Interpretation of previous studies

• Data on malignancy based on patient or physician questionnaires

• Reporting bias

• Follow-up limited to 5 years

• Observation period in most studies dated from the 1960s to the 1990

• Immunosuppressive therapy regimens have changed significantly

Current study

We investigated malignancies occurrence in 138 AAV patients treated with

current immunosuppressive therapy regimens, with a mean follow-up of 10

years.

Material & methods

• 138 patients with histopathologically confirmed AAV

• Primary malignancies were identified via the Dutch National Pathology

Database

• Nationwide accurate malignancy data reporting

• Malignancy occurrence was compared to that in the general population by

determining standardized incidence ratios (SIRs)

• National cancer incidence rate data provided by the Netherlands Cancer Registry

• Matching for sex, age (5-year age groups), and calendar-year period (1-year time

periods)

Included patients

Malignancy occurence

Subgroup analyses

• Increased malignancy risk in GPA and/or with PR3-ANCA as compared to

MPA/MPO-ANCA

• Malignancy risk not increased in patients treated after publication of

CYCAZAREM

• Three times less cyclophosphamide exposure

SIR according to cyclophosphamide treatment

Conclusion

• Malignancy risk is 2.21 times increased as compared to the general

population

• Attributable solely to the occurrence of NMSC

• No increased risk of other malignancies

• bladder cancer, leukemia, or malignant lymphomas

• Most likely reflect the changes in AAV treatment regimens over the years

• Malignancy occurrence directly associated with cyclophosphamide exposure

• Not increased in patients treated < 1 year

Rahmattulla et al. Arthritis & Rheumatology 2015

Acknowledgement

• Prof. dr. J.A. Bruijn (Department of pathology, LUMC)

• Dr. I.M. Bajema (Department of pathology, LUMC)

• S.W. Wakker (Department of pathology, LUMC)

• Dr. A.E. Berden (Department of internal medicine, LUMC)

• Dr. M.E.J. Reinders (Department of internal medicine, LUMC)

• Dr. M. Galli (Department of internal medicine, Medical Center Haaglanden)

• Dr. M. van Buren (Department of internal medicine, HagaZiekenhuis)

• Dr. H. Ablij (Department of internal medicine, Diaconessehuis)

• Dr. B. Gabreëls (Department of internal medicine, Rijnland Ziekenhuis)

• Dr. H. Peltenburg (Department of internal medicine, Groene Hart Ziekenhuis)

• Dr. H. Boom Department of internal medicine, (Reinier de Graaf Gasthuis)

• Dr. M. van Sandwijk (Department of internal medicine, Academic Medical Center)

• Dr. R. Nette (Department of internal medicine, Sint Franciscus Gasthuis)

• Dr. A. Lavrijssen (Department of internal medicine, Admiraal De Ruyter Ziekenhuis)

• Dr. M. G. H. Betjes (Department of internal medicine, Erasmus Medical Center, Rotterdam)