AN UPDATE ON THE OVERALL SAFETY AND INCIDENCE OF SPM IN LENALIDOMIDE-, THALIDOMIDE-, AND BORTEZOMIB-TREATED PATIENTS WITHIN THE EUROPEAN POST-APPROVAL SAFETY STUDY (EU PASS) OF RELAPSED/REFRACTORY MM

Sborník

Background. The efficacy and tolerability of lenalidomide in patients with relapsed or refractory multiple myeloma (RRMM) has been demonstrated in 2 large, randomized, phase 3 studies (MM-009 and MM-010). Bortezomib and thalidomide are also proven to be effective for the treatment of RRMM. Postapproval observational studies provide additional information on the safety of novel medications in real-world clinical practice. Aims. To compare the incidence of adverse events (AEs) of special interest, such as neutropenia, thrombocytopenia, venous thromboembolism (VTE), peripheral neuropathy (PN), and second primary malignancies (SPM) in patients treated with lenalidomide and other antimyeloma therapies for RRMM in a real-world setting. Methods. In this observational, non-interventional, post-authorization safety study, patients with MM who had received at least one prior therapy were enrolled into the lenalidomide cohort (lenalidomide plus dexamethasone, the approved combination for the treatment of RRMM) or the background. cohort (all other treatments, including other novel agents) at the investigator’s discretion. Thromboprophylaxis was allowed but not required. AEs were graded according to NCICTCAE (version 3) grading. Assessments for SPM were to be conducted up to 36 months after treatment discontinuation. Results. As of November 2011, 2,717 patients across 265 institutions, in 17 European countries were enrolled. Of those, 1,857 received lenalidomide, 670 received bortezomib, 101 received thalidomide, and 89 received other therapies or had missing data at time of analysis. Ninety-seven patients from the background. cohort crossed over following the physician’s decision to initiate lenalidomide treatment. Median follow- up for all groups was 24 weeks (range, 0.6-157.3). Median age was 69 years (range, 29-95) and 54% were male. Most patients (66%) had good performance status (ECOG score 0-1); 17% had an ECOG score of 2-4. Median number of prior therapies was 2 (range, 0-6): 52% had 2 prior therapies and 22% had ≥3 prior therapies. Baseline characteristics were similar between groups. Overall, 1,189 (45%) had an AE of grade 3-4. Grade 3-4 neutropenia occurred in 19%, 7%, and 15% of patients in the lenalidomide, bortezomib, and thalidomide groups, respectively. Grade 3-4 thrombocytopenia developed in 16%, 14%, and 9% of patients, respectively. The overall incidence of peripheral neuropathy was 27% (4% grade 3-4) in the bortezomib group compared with 7% (1%) in the lenalidomide and 13% (1%) thalidomide groups. Grade 3- 4 VTE developed in 2% of patients in the lenalidomide group and none in the other two treatment groups. The overall treatment discontinuation rate was 63%, 79%, and 78% in the lenalidomide, bortezomib, and thalidomide groups, respectively, with a similar discontinuation rate due to AEs in each group. The incidence of SPM was ≤1% overall (Table). Incidence of death during the study was similar with all treatments (lenalidomide 6%, bortezomib 5%, and thalidomide 5%). Conclusions. Lenalidomide has been shown to improve disease outcomes in RRMM patients. AEs, including SPM, were similar with all treatments except for higher rates of neutropenia and lower rates of PN with lenalidomide, compared with patients receiving bortezomib or thalidomide.

Table. Summary of SPM (*indicates same patient).

Haematologica, 2012; 97(s1):  340