difference between the two assessments relates to a marginally greater improvement in OS benefit with Rd relative to MPT in patients with NDMM not eligible for stem cell transplantation (Study MM-020) based on the second round assessment compared to the first round assessment (25% versus 22%, respectively). Second round assessment of risks Following consideration of the sponsor’s Section 31 Response to the round clinical questions and the first round clinical evaluation report the second round assessment of risks remains unchanged from that provided in the first round. Second round assessment of benefit-risk balance Following consideration of the sponsor’s Section 31 Response to the first round clinical questions and the first round clinical evaluation report the second round assessment of the benefit-risk balance remains unchanged from that provided in the first round. Second round recommendation regarding authorisation Following consideration of the sponsor’s Section 31 Response to the round clinical questions and the first round clinical evaluation report the second round recommendations regarding authorisation remain unchanged from those provided in the first round. The reasons for the recommendations remain unchanged from those provided in the first round. It should be noted that approval is recommended for Revlimid in combination with dexamethasone for the treatment of patients with NDMM who are not eligible for stem-cell transplantation. It is recommended that the following lenalidomide dosage regimen be approved for this indication: Lenalidomide 25 mg QD on days 1-21 of repeated 28 day cycles with dexamethasone 40 mg QD on days 1, 8, 15, and 22 of repeated 28 day cycles. V. Pharmacovigilance findings Risk management plan The sponsor submitted EU-RMP Version 23 (dated 10 February 2014, DLP 26 December 2012) and Australian Specific Annex (ASA) Version 1.0 (dated 10 February 2014). Safety specification The sponsor provided a summary of ongoing safety concerns are shown at Table 9. Table 9: Ongoing safety concerns. Important identified risks Teratogenicity Thrombocytopenia and bleeding Neutropenia and infection Thromboembolic events Cutaneous reactions Hypersensitivity and angioedema
Table 10: Ongoing safety concerns. Additional activity Assigned safety concern Actions/outcome proposed Estimated planned submission of final data RRMM PASS (ongoing) Safety profile in a ‘real world’ setting, foetal exposure (teratogenicity, Important identified risk) To monitor safety in a “real world” situation. Annual safety updates submitted with the PSUR MDS PASSes (presumed ongoing) [European Safety profile in a ‘real world’ setting, off-label use (Important potential risk) To gather safety data on the use of lenalidomide in MDS patients and monitor use (prospective disease registry in transfusion-dependent and INT-1-risk MDS with an isolated del 5q and a retrospective drug utilisation study of Revlimid in MDS). Annual safety updates submitted with the PSUR Pooled analysis of data from clinical trials of Revlimid Thromboembolic events (Important identified risk) To determine the incident of VTEs and ATEs in patients with MM, with consideration of the thromboprophylactic agents used. To be submitted in the next PSUR update. NDMM CONNECT Registry (ongoing) [United States] AML and B-cell malignancies (identified/potential risk) Non-melanoma skin cancer (identified/potential risk) Other Second Primary Malignancy (Important potential risk) The primary objectives of the registry will be to describe practice patterns of common first-line and subsequent treatment regimens (including lenalidomide-based) as well as diagnostic patterns and SPM occurrence in the community and academic settings. Additionally, the registry will provide insight into treatment regimens and therapy sequence in clinical practice as they relate to clinical outcomes (response, overall survival, progression free survival) in patients with symptomatic NDMM. Annual safety updates submitted with the PSUR CONNECT MDS/AML Registry (presumed Other second primary malignancy The primary objectives of the registry will be to describe practice patterns of common first-line treatment Annual safety updates submitted with the PSUR.