Guidelines for the correct determination of second primary malignancies (SPM) in myeloma trails Background and update from Myeloma XI Dr John Jones Myeloma Clinical Research Fellow Institute of Cancer Research, London

SPMs in myeloma Older age, myeloma and MGUS risk factors for malignancy Myeloma survival improving with a trend towards continuous therapy resulting in ↑drug exposure. Three studies published in 2012 suggested an increased SPM incidence with lenalidomide maintenance treatment. McCarthy et al. Len after SCT for MM. NEJM. 2012 Palumbo A et al. Continuous len for NDMM. NEJM. 2012 Attal M et al. Len maintenance after SCT for MM. NEJM. 2012

Meta-analysis Increased risk of haematological SPMs mainly associated with lenalidomide given in combination with oral melphalan: Cumulative incidence of solid and haematological second primary malignancies: 7.2% 5yrs Palumbo A et al, Lancet Oncol 2014; 15: 333-42

Myeloma XI len used as induction + maintenance treatment Correct identification of trial related SPMs essential. Rejection criteria 1 Malignancy was present prior to diagnosis. 2 Pre-malignant condition 3 Developed in first cycle of treatment 4 Recurrence of previous malignancy 5 Initial report found to be incorrect 6 Spontaneous resolution of disease

MXI SPM committee outcome 88 reported SPM 67 accepted 21 rejected Overall incidence – 2.45% Haem incidence – 0.29% Of the 67 cases 52 had received lenalidomide at some point. 12 pre-dated trial 5 not malignancy 3 non malignant condition 1 resolved

Conclusions There is a need for the correct identification of SPMs to provide accurate risk to patients We have shown that thorough review of each case has led to the rejection of over 20% of cases We therefore recommend the incorporation of a review process into all trials where SPM risk is deemed to be an associated risk factor.