Second malignancies in the context of lenalidomide treatment: an analysis of 2732 myeloma patients enrolled to the Myeloma XI trial

Abstract

We have carried out the largest randomised trial to date of newly diagnosed myeloma patients, in which lenalidomide has been used as an induction and maintenance treatment option and here report its impact on second primary malignancy (SPM) incidence and pathology. After review, 104 SPMs were confirmed in 96 of 2732 trial patients. The cumulative incidence of SPM was 0.7% (95% confidence interval (CI) 0.4–1.0%), 2.3% (95% CI 1.6–2.7%) and 3.8% (95% CI 2.9–4.6%) at 1, 2 and 3 years, respectively. Patients receiving maintenance lenalidomide had a significantly higher SPM incidence overall (P=0.011). Age is a risk factor with the highest SPM incidence observed in transplant non-eligible patients aged >74 years receiving lenalidomide maintenance. The 3-year cumulative incidence in this group was 17.3% (95% CI 8.2–26.4%), compared with 6.5% (95% CI 0.2–12.9%) in observation only patients (P=0.049). There was a low overall incidence of haematological SPM (0.5%). The higher SPM incidence in patients receiving lenalidomide maintenance therapy, especially in advanced age, warrants ongoing monitoring although the benefit on survival is likely to outweigh risk.

Lenalidomide vs bortezomib maintenance choice post-autologous hematopoietic cell transplantation for multiple myeloma

“…There are many potential factors that may impact the risk of SPM, including effects from previous cancer treatment, host factors, and genetic predisposition [32,33]. An individual risk-benefit analysis for continued therapy should be conducted for each myeloma patient [34][35][36], and physicians and patients should make an informed decision together.…”

Realistic Lenalidomide Dose Adjustment Strategy for Transplant-Ineligible Elderly Patients with Relapsed/Refractory Multiple Myeloma: Japanese Real-World Experience

“…We think that this strategy is sensible as we did not have to stop treatment because of adverse events. Evidence is emerging that continuous treatment can improve progression-free survival and OS [10]. …”

“…Although this rate is higher than normal, it is uncertain whether it is related to lenalidomide or the original nature of myeloma [10,13]. …”

Prevention and management of adverse events of Novel agents in multiple myeloma: A consensus of the european myeloma network

“…Lenalidomide therapy is associated with an increased risk for second primary malignancies, especially in the post-transplantation setting, [24][25][26] or after a melphalan-containing regimen, 27 and after an IMiD-based induction therapy. 28 Data from the latter study show a cumulative incidence of 0.7%, 2.3%, and 3.8% after 1, 2, and 3 years, with the highest incidence in elderly patients. Lenalidomide is to a substantial degree excreted by the kidney and the dose has to be adapted to glomerular filtration rate.…”