Myeloma XI Trial – Second Primary Malignancy Interim Report in Newly Diagnosed Multiple Myeloma (NDMM) Patients

• Published in: Blood 2014-12, Vol.124 (21), p.4744-4744
• Main Authors: Jones, John, Pawlyn, Charlotte, Brioli, Annamaria, Cairns, David A, Quartillo, Ana, Sigsworth, Rachel, Howard, Helen, Collett, Corinne, Ouzman, Jacqueline, Gregory, Walter, Russell, Nigel, Jackson, Graham H, Davies, Faith E, Morgan, Gareth J.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V124.21.4744.4744

▪ Background: Past studies have linked lenalidomide to an increased risk of second primary malignancy (SPM) and in-particular a higher incidence of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). Such studies in which oral melphalan was used in combination with lenalidomide resulted in haematological SPM incidence of between 3.0-11.4% at 5 years. More recently, meta-analysis has suggested that lenalidomide in combination with other agents such as cyclophosphamide and dexamethasone does not result in an increased rate of SPM development. Here we report the incidence of SPM in Myeloma XI, the largest randomised trial to date in-which lenalidomide is used as both an induction and maintenance treatment option. Methods: Myeloma XI is a phase III, randomised, multi-centre, parallel group design, open-label trial comparing thalidomide, lenalidomide and bortezomib combinations and lenalidomide as maintenance treatment in newly diagnosed symptomatic myeloma patients. The trial has both transplant eligible (TE) and transplant non-eligible (TNE) pathways. NDMM patients are entered into the TE pathway if they are deemed fit/young enough to tolerate high dose therapy. Those who enter the TNE pathway receive attenuated doses of chemotherapy agents. Patients in the TE pathway will receive high dose melphalan supported by autologous stem cell transplantation if they achieve a very good partial response or better following induction or, if appropriate following pre-transplant consolidation. Pre-transplant consolidation with bortezomib is protocol treatment for patients with refractory disease or no change post-induction whereas for patients with a sub-optimal response (MR/PR) randomisation to bortezomib versus observation alone is compared. Both pathways include maintenance with lenalidomide, lenalidomide and vorinostat or monitoring only. Since May 2010, 2745 patients have been recruited with over 950 patients enrolled for more than 2 years since initial induction randomisation. A total of 1225 patients have entered maintenance with 720 receiving lenalidomide maintenance either as a single agent or in combination with vorinostat. Results: Thirty three patients (1.2% of entrants) have developed a second primary malignancy since enrolment. One patient developed a haematological SPM (CML) whilst on the trial (0.04%). This occurred in a patient being treated on the TE pathway who had received lenalidomide containing induction and had undergone 24 months of l