PS1421 HONEUR (HEAMATOLOGY OUTCOMES NETWORK IN EUROPE) – DISTRIBUTED STATISTICS IN A FEDERATED MODEL TO SUPPORT REAL WORLD DATA RESEARCH IN HEMATOLOGY
Authors: A. Passey, N.J. Perualilia, K. Bardenheuer, T. Verbeke, V. Nassiri, M. Van Speybroeck
Journal: HemaSphere (2019)

Background: Lenalidomide (LEN)-based treatment (Tx) until disease progression is a standard approach for many newly diagnosed multiple myeloma (NDMM) patients (pts). The safety and efficacy of this approach in transplant-ineligible NDMM pts has been validated in multiple clinical trials, including the phase 3 FIRST trial. Aims: This observational, non-interventional post-authorization safety study (PASS; NCT03106324) is investigating the safety and tolerability of LEN-based Tx (LEN cohort) compared with non–LEN-based Tx (non-LEN cohort) in transplant-ineligible NDMM pts, including adverse events (AEs) of interest and second primary malignancies (SPMs). Methods: This ongoing PASS is enrolling transplant-ineligible NDMM pts initiating their first antimyeloma Tx. Pts already receiving Tx at the time of enrollment are eligible if they have received < 2 cycles. Tx is per routine clinical practice and is determined before enrollment in the trial. The observation period for patients on Tx is up to 3 years, with a follow-up period of 5 years, during which SPMs and survival will be assessed. The primary endpoint is incidence of cardiovascular events. Secondary endpoints are incidences of renal impairment, infections, and SPMs, as well as further characterization of safety. Results: As of 10 December 2018, 116 pts were enrolled in the LEN cohort and 119 pts were enrolled in the non-LEN cohort. Bortezomib-based Tx was the most common Tx in the non-LEN cohort. Median age was 79.0 yrs in the LEN cohort and 76.0 yrs in the non-LEN cohort. ISS stage I/II/III was 16.4%/22.4%/21.6% in the LEN cohort and 10.9%/24.4%/29.4% in the non-LEN cohort. Tx was ongoing in 86 pts (74.1%) and 77 pts (64.7%), respectively. There were 6 (5.2%) cardiovascular events in the LEN cohort: 2 (1.7%) angina pectoris, and 1 (0.9%) each of troponin increased, cardiac failure congestive, cardiovascular insufficiency, and acute pulmonary edema. Eight (6.7%) cardiovascular events were reported in the non-LEN cohort: 4 (3.4%) cardiac failure, 2 (1.7%) myocardial infarction, and 1 (0.8%) each of arterial bypass occlusion and cardiopulmonary failure. Rates of grade 3/4 AEs were generally low (Table 1). Similar proportions of pts in both cohorts experienced ≥ 1 grade 3/4 AE (LEN cohort, 38.8%; non-LEN cohort, 41.2%), but the proportions of pts who experienced ≥ 1 AE leading to death was higher in the non-LEN cohort (10.1%) than in the LEN cohort (5.2%). In the LEN cohort, 51 pts (44.0%) had ≥ 1 AE related to LEN. LEN discontinuations and reductions or interruptions due to ≥ 1 AE occurred in 11 pts (9.5%) and 48 pts (41.4%), respectively. In both cohorts, there were 2 solid tumor SPMS (LEN, 1 lung cancer and 1 prostate cancer; non-LEN, 1 lung cancer and 1 bladder cancer). Both cohorts had 1 nonmelanoma skin cancer (squamous cell carcinoma); this was a recurrence in the non-LEN cohort. There were no reported hematologic SPMs.Summary/Conclusion: The current results of this ongoing observational, non-interventional study demonstrate that LEN-based Tx in transplant-ineligible NDMM pts in a real-world setting has a safety profile consistent with what has been observed in clinical trials. The incidence of cardiovascular events and other AEs was low, and no new safety signals for LEN-based Tx have been identified.