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ASH 2011: Dr. Palumbo - Melphalan/Prednisone/Lenalidomide (MPR) Versus High-Dose Melphalan and Autologous Transplantation (MEL200) in Newly Diagnosed Multiple Myeloma (MM) Patients <65 Years: Results of a Randomized Phase III Study
Antonio Palumbo, MD
University of Torino
AOU S. Giovanni Battista
Torino, Italy

Background: The risk of developing a tumor is 2.1% per year of life in the general population older than 65 years. In MGUS, the incidence of AML/MDS is increased 8 fold compared with normal population, this observation supports a role for non-treatment related factors in the causation of AML/MDS in plasma-cell dyscrasias (Blood, July 27,2011). In multiple myeloma (MM) patients, the risk of second primary malignancy (SPM) is influenced by age and the use of alkylating agents.

Methods: We examined SPM incidence rates (IRs) per 100 person-years in 2459 newly diagnosed MM patients, enrolled in 9 experimental trials of the European Myeloma Network (RVMM EMN 01, RVMM EMN 441, RVMM PI 026, RVMM PI 302, RVMM PI 209, GIMEMA MM 03 05, GIMEMA MM 04 05, GISMM 2001, HOVON 87). 287 patients received cyclophosphamide-lenalidomide-corticosteroids (CRC), 685 melphalan-prednisone-lenalidomide (MPR), 484 high-dose melphalan followed by lenalidomide maintenance (MEL200-R), 164 melphalan-prednisone (MP), 328 MP-thalidomide (MPT), 257 MP-bortezomib (MPV), 254 MP-bortezomib-thalidomide (VMPT). This post hoc analysis was restricted on pooled data from 1798 patients with at least 1 year of follow-up.

Results: As of March 2011 cut-off, median follow-up was 28 months. Median age was 69 years, 49% of patients were aged 65-74 years, and 19% aged ≥75 years. Total cases of SPMs were 30/1798 (IR 0.72), including 8 hematologic (acute leukemia) and 22 solid cancers (gastrointestinal, lung, breast, skin, gynecologic). No cases of SPMs were reported in patients receiving cyclophosphamide and lenalidomide.

In patients receiving lenalidomide and alkylating agents (CRC/MPR/MEL200-R), the cumulative incidence of death for MM and diagnosis of SPMs at 3 years was 13.8% and 2.0%, respectively. In patients not receiving lenalidomide (MP/MPT/MPV/VMPT), the cumulative incidence of death and SPMs at 3 years was 26.1% and 1.1%, respectively. In the analysis restricted to Italian patients treated with lenalidomide and alkylating agents, we report 11 cases of SPMs. This figure is lower than the 15.6 cases expected from the age/sex adjusted incidence derived form the Italian Cancer Registry, with a standardized incidence ratio of 0.70.

Conclusions: SPM incidence was lower than expected in all treatment groups. At present, the benefits of continuous therapy with lenalidomide outweigh the potential risk of SPMs. Longer follow-up is needed to definitively assess the risk of SPMs in patients receiving lenalidomide with alkylating agents. With the limitation of a short follow-up, the numbers currently support a role for non-treatment related factors as causes of SPMs. Updated data will be presented at the meeting.

Table. Clinical outcome after MPR or MEL200 consolidation





P value













      2-year PFS




      2-year OS




Standard-risk patients




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High-risk patients




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Patients who achieved CR




      2-year PFS




Patients who achieved PR




      2-year PFS




Disclosures: Palumbo: celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Off Label Use: The presentation includes information of off-label use of Lenalidomide during induction, consolidation and maintenance therapy in newly diagnosed multiple myeloma patients younger than 65 years. . Cavallo: Celgene: Honoraria; Janssen-Cilag: Honoraria. Cavo: celgene: Honoraria. Ria: celgene: Consultancy. Caravita Di Toritto: Celgene: Honoraria, Research Funding. Di Raimondo: celgene: Honoraria. Boccadoro: celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

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