1. 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

2. 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

3. 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:

4. 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

5. 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

6. 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.