
Melanoma complicating treatment with natalizumab for multiple sclerosis: A report from the Southern Network on Adverse Reactions (SONAR)
Author(s) -
Sabol Rachel A.,
Noxon Virginia,
Sartor Oliver,
Berger Joseph R.,
Qureshi Zaina,
Raisch Dennis W.,
Norris LeAnn B.,
Yarnold Paul R.,
Georgantopoulos Peter,
Hrushesky William J.,
Bobolts Laura,
Ray Paul,
Lebby Akida,
Kane Robert C.,
Bennett Charles L.
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1098
Subject(s) - natalizumab , medicine , multiple sclerosis , melanoma , adverse effect , adverse event reporting system , surgery , oncology , immunology , cancer research
A 43‐year‐old female with multiple sclerosis developed urethral melanoma. The only potential risk factor was treatment with natalizumab, a humanized monoclonal antibody against α 4 integrins. To investigate the risk‐exposure relationship, we reviewed this case, all other published cases, and cases of natalizumab‐associated melanoma reported to regulatory agencies. Data sources included the Food and Drug Administration's ( FDA ) Adverse Event Reporting System ( FAERS ) (2004–2014), a FDA Advisory Committee Meeting Report, and peer‐reviewed publications. In the United States, the manufacturer maintains an FDA ‐mandated Tysabri Safety Surveillance Program (part of the Tysabri Outcomes Unified Commitment to Health ( TOUCH )) of natalizumab‐treated patients. We statistically compared reporting completeness for natalizumab‐associated melanoma cases in FAER s for which information was obtained entirely from the TOUCH program versus cases where FAERS information was supplemented by TOUCH program information. FAERS included 137 natalizumab‐associated melanoma reports in patients with multiple sclerosis. Median age at melanoma diagnosis was 45 years (range: 21–74 years). Changes in preexisting nevi occurred in 16%, history of cutaneous nevi occurred in 22%, diagnosis within 2 years of beginning natalizumab occurred in 34%, and 74% had primary surgical treatment. Among seven natalizumab‐treated MS patients who developed biopsy‐confirmed melanoma on treatment and reported in the literature, median age at diagnosis was 41 years (range: 38–48 years); and the melanoma diagnosis occurred following a median of 12 natalizumab doses (range: 1–77 doses). A history of mole or nevi was noted in four patients and a history of prior melanoma was noted in one patient. Completeness scores for reports were significantly lower for FAERS cases reported from the TOUCH program versus FAERS cases supplemented by TOUCH information (median score of 2 vs. 4 items out of 8‐possible items, P < 0.0007). Clinicians should monitor existing nevi and maintain suspicion for melanoma developing in natalizumab‐treated patients. The TOUCH Safety Surveillance Program, currently focused on progressive multifocal leukoencephalopathy, should be expanded to include information on other serious complications including malignancies, particularly if they are immunologic in nature.