Second primary malignancies in patients receiving treatment with ruxolitinib for myelofibrosis – a regional experience
Published Date: 01st May 2020
Publication Authors: Nicholson T
Patients with myeloproliferative neoplasms (MPN) are at an increased risk of second primary malignancies (SPM) compared with matched‐controls and the general population. The Surveillance, Epidemiology and End Results (SEER) database (US cancer registries) reported that patients with primary myelofibrosis (PMF) had an incidence of SPM of 5·3% after a median duration of 1·8 years (range 0·04–9·1 years). These patients were at increased risk of respiratory malignancies and lymphoma when compared with the US general population.
Ruxolitinib (Jakavi, Novartis) is a protein kinase inhibitor that targets Janus‐associated kinase (JAK) signalling and is approved for use in selected adults with primary and secondary myelofibrosis (PMF). There is conflicting published data for the occurrence of SPM in ruxolitinib treated MF patients. There appears to be a possible increased incidence of non‐melanoma skin cancers (NMSC) in these patients but the risk of other SPM is less clear.
We undertook an audit of our regional experience of SPM in ruxolitinib treated MF patients. Local Trusts within the Cheshire & Merseyside Cancer Alliance were invited to participate. All patients with a diagnosis of PMF or secondary MF who had received ruxolitinib were included for analysis. Data were collected and analysed for patient demographics, disease characteristics, past history of malignancy, duration of ruxolitinib therapy and any occurrences of SPM whilst on therapy.
There were 29 patients (male = 19, female = 10) included in the audit covering a 6 years period (January 2013 to September 2019). Of these, 15 had PMF and 14 had secondary MF. The median age at diagnosis was 73 years (range 35–94 years). Four patients had a past history of malignancy prior to ruxolitinib exposure. These included: NMSC (n = 3), breast cancer (n = 1 – this patient also had concurrent NMSC) and bladder carcinoma (n = 1). The median age at commencement of ruxolitinib was 73 years (range 47–94 years). The median duration of treatment was 18 months (range 2–79 months). The total duration of ruxolitinib exposure across the entire cohort was 60 years. SPM were seen in 6 patients (21%). The median duration of treatment prior to SPM diagnosis was 19 months (range 12–63 months). The SPM diagnoses were as follows: NMSC (n = 2), oropharyngeal basaloid squamous cell carcinoma (SCC, n = 1), diffuse large B‐cell lymphoma (DLBCL, n = 1), SCC of the lung (n = 1) and myelodysplastic syndrome with multi‐lineage dysplasia (n = 1). The case of DLBCL did not have a preceding history of lymphoproliferative disorder. Four patients with SPM (67%) had no prior history of malignancy. One patient with previous NMSC developed multiple aggressive NMSCs after commencing ruxolitinib with the suspicion of a pulmonary metastasis. The case of the SCC of the lung originated from a previously stable lung nodule that had been under surveillance for 5 years. After 24 months of ruxolitinib the lung nodule progressed into lung carcinoma and the patient died 12 months later secondary to this.
Our regional audit confirms the increased incidence of SPM in ruxolitinib treated MF patients when compared to the SEER comparison population (21% versus 5·3%). This is comparable to other published data. On this basis, we counsel all patients being considered for ruxolitinib for MF of the risk of NMSC and the potential risk of other SPMs. A larger UK audit of real world incidence of SPM in ruxolitinib treated MF patient would be valuable.
Scholfield, J; Wells, R; Nicholson, T; Butt, NM. (2020). Second primary malignancies in patients receiving treatment with ruxolitinib for myelofibrosis – a regional experience. British Journal of Haematology. 189 (S1),