Background: As survival improves, SPMs have become an increasingly important safety consideration for RRMM patients. Alkylators, autologous stem cell transplantation, and immunomodulatory drugs (IMiDs), specifically lenalidomide, are known to increase SPM risk. Patients who are TCE (exposure to ≥1 IMiD, ≥1 proteasome inhibitor, and ≥1 anti-CD38 monoclonal antibody [mAb]) represent an increasingly large subgroup of RRMM patients.
Objectives: To describe the incidence of SPMs in patients with TCE RRMM. These data may inform development and selection of novel treatments for these patients.
Methods: Data were from two US insurance claims databases: the Optum Clinformatics® Data Mart and the IQVIA PharMetrics® Plus Claims database. Patients were selected if they had ≥1 confirmed diagnosis of multiple myeloma (MM) in the claims on or after December 1, 2015 (US Food and Drug Administration approval date of 1st anti-CD38 mAb for RRMM) and evidence of being TCE. The first line of therapy (LOT) after becoming TCE was identified (date of initiation = index date). Patients with SPMs prior to the index date were excluded. SPMs were identified based on ≥1 inpatient or ≥2 outpatient diagnoses (of the same cancer type) of invasive malignancies or myelodysplastic syndromes (MDS) other than MM, Waldenstrom macroglobulinemia, plasma cell leukemia, non-melanoma skin cancers, or primary bone malignancies preceded by a diagnosis of bone metastases. SPM incidence was calculated per 100 person years (PY), based on the first SPM for each patient. Cumulative incidence of SPM with death as competing risk was calculated in Optum database (mortality data unavailable in the PharMetrics).
Results: 1,110 TCE RRMM patients were identified in the two databases. Among those with no SPM prior the index date (N=726), mean age was 66.6 y and 45% were female, with a mean of 3 prior LOTs and 3.2 years since diagnosis. Over a mean (SD) follow-up of 11.7 (10.4) months, 96 patients (14.8 per 100 PY) experienced a new SPM, including 47 (7.2 per 100 PY) with first SPM of solid tumor (top 3: 7 lung, 6 prostate, 5 colon/5 breast) and 51 (7.9 per 100 PY) with a first SPM of hematologic malignancy (top 3: 22 acute myeloid leukemia [AML], 17 MDS, 8 non-Hodgkin lymphoma). In the Optum database (N=416), the estimated cumulative incidence of SPM (95%CI) was 10.3% (7.4, 13.7), 14.9% (10.8, 19.6), and 20.1% (13.9, 27.2) at 12, 24, and 36 months, respectively.
Conclusions: SPM incidence in TCE RRMM patients is clinically significant, including the majority of hematological SPM being AML and MDS. Future research is warranted to assess disease- and treatment-related factors contributing to SPM. There is a need for effective treatments for TCE RRMM that are not associated with increased risks of SPMs.
