Risk of second primary malignancy in patients with AL amyloidosis treated with lenalidomide
Authors: Vaishali Sanchorawala, Anthony C. Shelton, Jerome B. Zeldis, David C. Seldin
Journal: American Journal of Hematology (2013)

Second primary malignancy (SPM) is a growing issue for cancer survivors 1, 2. SPM has been associated with radiation therapy, anthracyclines, alkylating agents, and topoisomerase inhibitors 3. Recently an increased incidence of invasive SPM has been observed with lenalidomide (7.6%) compared with controls (2.9%) in patients with newly diagnosed myeloma receiving lenalidomide in combination with melphalan 4 or as long-term maintenance therapy following high-dose melphalan with autologous stem cell transplantation 5, 6. In a retrospective pooled analysis of 11 clinical trials of lenalidomide-based therapy for relapsed/refractory myeloma, the overall incidence rate (IR, events per 100 patient-years) of invasive SPM was 2.08 7. Lenalidomide treatment can be effective in AL amyloidosis. In 2007, our group and the Mayo Clinic described promising results of phase 2 trials 8, 9. In view of emerging data on SPM in myeloma with lenalidomide treatment, we performed a post hoc analysis for the incidence of SPM in the patients with AL amyloidosis treated with lenalidomide at Boston Medical Center. Occurrence of SPM was reported by the patient and/or referring physician and confirmed by the site by reviewing the pathology. Between 2004 and 2011, 82 patients with AL amyloidosis were treated with lenalidomide and dexamethasone (ClinicalTrials.gov: NCT00091260) 9. The median age was 62 years (range, 40–82) and 63% were male. Seventy-eight patients (95%) had received prior therapy (94% prior melphalan-based therapy). The median duration of lenalidomide treatment was nine cycles (range, 1–69). Sixteen (20%) patients received lenalidomide treatment for > 24 months. Hematologic response was evaluated in 68 patients after completion of three cycles of therapy; patients who withdrew from the study or who had not completed at least three cycles were not evaluable for response assessment. A complete hematologic response was seen in 11 patients (16%) and a partial hematologic response was seen in 30 patients (44%), for an overall response rate of 60%. The median time to best hematologic response was 6 months. Thirty patients (44%) had a measurable organ response. The median overall survival is not yet reached with a median follow-up for 32 months (range, 3–92). Six patients were noted to develop SPM. The total follow-up was 2.46 per 100 patient-years. One patient developed primary lung cancer with metastases after 24 months of lenalidomide therapy; he was a cigarette smoker and had prior treatment with oral melphalan. Additionally, five patients developed nonmelanoma skin cancer. There were no cases of hematologic malignancy or B-cell lymphoproliferative disorder. Therefore, the IR of invasive cancer (without nonmelanoma skin cancers) was only 0.44 per 100 patient-years (95% CI, 0.05–2.88) in this trial. This compares favorably to the annual incidence of invasive cancers in the United States for the general population. Age-specific IRs of invasive cancers across all sites identified through the SEER program are 1.26 among persons aged 60–64 years; 1.74 among persons aged 65–69 years; 2.09 among persons aged 70–74 years; 2.39 among persons aged 75–79 years; 2.46 among persons aged 80–84 years; and 2.18 among persons aged ≥ 85 years 10. In summary, lenalidomide-based treatment in AL amyloidosis did not appear to increase the IR for invasive SPM compared to the IR for invasive cancers in general population. Longer follow-up and additional patient accrual may be needed to better define the risk of SPM in this patient population. This clinical trial was funded by Celgene Corporation. Vaishali Sanchorawala,1,2 Anthony C. Shelton,1 Jerome B. Zeldis,3 and David C. Seldin1,2 1Section of Hematology-Oncology, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts 2Amyloidosis Center, Boston University School of Medicine, Boston, Massachusetts 3Celgene Corporation, Summit, New Jersey