Development of Second Primary Malignancies in Multiple Myeloma Patients Treated with Lenalidomide: An Alberta Perspective

Background: Use of immunomodulatory agents such as lenalidomide have increased overall survival rates in multiple myeloma patients, but has been linked to increased development of second primary malignancies (SPM). The estimated incidence of SPM in multiple myeloma patients treated with lenalidomide ranges from 2.3- 7.2% in the literature.

Objectives: The primary objective of this study was to identify the proportion of patients in Alberta who used lenalidomide to treat multiple myeloma and developed a SPM. Secondary objectives were to evaluate the types of SPM that occurred, examine duration of lenalidomide therapy, evaluate the impact of exposure to other immunomodulatory agents, alkylating agents, radiation therapy and stem cell transplant on the development of SPM, and compare overall survival between patients with and without a SPM.

Methods: A retrospective chart review was conducted using the electronic medical record system ARIA Medical Oncology, the Alberta Cancer Registry, and the pharmacy dispensing system BDM Pharmacy from January 1, 2008 to June 30, 2015. Patients were eligible to be included if they received at least one dose of lenalidomide for multiple myeloma during the study timeframe and were ≥ 18 years of age. In addition to patient demographics, data collected included date and cause of death, cancer diagnoses prior to multiple myeloma, diagnosis of SPM, duration of lenalidomide therapy, and treatment with other immunomodulatory agents, alkylating agents, radiation therapy and stem cell transplantation. Non-invasive malignancies, such as squamous cell and basal cell carcinoma were excluded from the primary outcome.

Results: A total of 777 charts were reviewed, of which 768 patients were included. The average age at diagnosis was 63.7 years (33 - 89 years), and 59.8% were male. Mean duration of follow up from the start of lenalidomide therapy was 27 months (1 -144 months). The average number of lenalidomide cycles received was 19 (1 - 121 cycles). There were 41 SPM, including 30 solid tumours and 11 hematological SPM, that developed in 35 lenalidomide treated patients resulting in an occurrence rate of 5.3%. Five patients developed more than one SPM, with one patient found to have as many as three different SPM. No difference was identified in the rate of SPM in patients who received alkylating agents, other immunomodulatory agents or radiation therapy. Patients who developed a SPM received treatment for a longer duration (26.5 vs. 19 mean cycles, p= 0.021) and were less likely to have had a stem cell transplant (34.3% vs. 52.3%, p=0.038). Prior to the diagnosis of myeloma, 127 malignancies had been diagnosed in 107 patients, and was similar between the two groups (22.9% vs. 13.5%, p=0.086). There was no difference found in overall survival between those patients with a SPM and those without (96.9 vs. 95.0 mean months, p=0.872).

Conclusions: In this population-based study, rates of SPM identified in Alberta were similar to rates reported in the literature and overall patient survival was not found to differ between patients who developed a SPM and those who did not. Patients that developed a SPM received more cycles of lenalidomide and were less likely to have had stem cell transplant. There appeared to be higher rates of SPM in those patients who had a malignancy diagnosed prior to the development of multiple myeloma, but the difference was not statistically significant. Further research is needed to investigate the correlation between the development of a SPM and the number of malignancies found prior to being diagnosed with multiple myeloma.