P890: THE OUTCOME OF SECOND PRIMARY MALIGNANCIES DEVELOPING IN MM PATIENTS

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Background: The continuing improvement in response rates and overall survival (OS) of multiple myeloma (MM) patients exposed to the cumulative effect of multiple anti-MM agents including IMiDs, PIs, mAbs and cytotoxic chemotherapy, has resulted in an increased risk for second primary malignancies (SMPs). There is minimal detailed information regarding the clinical characteristics of patients who develop SPMs, risk factors predicting development, time to onset, SPM’s management and outcomes in patients treated with novel agents outside clinical trials. Aims: To investigate the characteristics and outcome of SPMs reported in MM patients and define impact of SPM diagnosis on MM management and outcome. Methods: A multicenter international ‘real-world’ retrospective analysis, reviewing MM databases of 25 participating centers and analyzing the characteristics and outcome of SPM reported in patients that were treated with novel-based induction. In addition, the impact of SPM diagnosis on MM management and outcome are reported. Results: Two hundred and one consecutive MM patients, experiencing SPM ≥ 6 months since initiation of first line therapy were included in the analysis. Clinical characteristics included the following: 64% were male, median age at 66±10.57 years, 10% with a prior history of cancer. 36% and 25% of evaluable cases presented with high ISS-3 and high-risk cytogenetics. 87(43%) underwent an autologous hematopoietic cell transplantation and 51(27%) received maintenance therapy. Median number of lines of therapy prior to SPM defection was 2 (1-7). With a median follow-up of 50± 45 months since MM diagnosis, 115 patients (57%) were diagnosed with solid cancers: colorectal cancer (n=20, 17.4%), lung (n=18, 15.6%), breast (n=14, 12%), prostate (n=8, 7%), melanoma (n=10, 9%), pancreas (n=10, 9%), bladder (n=7, 6%) and gastric (n=7, 6%), skin cancer (n= 34, 16.9%) and cancer of unknown origin (n=9, 4.5%). 46 patients (22.9%) developed hematological cancers, including lymphoma and MDS/AML; reported in 7(6%) and 27 (13.4%) cases respectively. 79% (n=158) were actively treated for SPM and 39.5% responded to therapy. Forty Eight percent (n=98) of the patients were concurrently receiving an anti-MM therapy at the time of SPM diagnosis. MM treatment remained unchanged in 27 patients, discontinued and not substituted with any other anti-MM therapy until MM progression in 59 patients and changed to a new anti-MM therapy in 12 patients. Within a median follow-up period of 112 months since MM diagnosis and 31 months since SPM detection, 50.5% (n-101) have died; 32 due to solid cancer (32/101, 28%), 11 due to hematological cancer (11/46, 24%) and 13 (6%) due to MM progression. Cause of death was not available for 45 cases. Median OS since MM diagnosis and since SPM detection were 63 months and 8.5 months, respectively (Figure 1). (Detailed analysis regarding causes of death and risk factors to be presented at the meeting). Image:Summary/Conclusion: With the continuing improvement in OS, a higher proportion of MM patients are likely to develop SPM. OS since SPM diagnosis is shortened, approaching 8.5 months only, suggesting that the SPMs, originating in this scenario, are generally aggressive. Surveillance for early detection and treatment of SPMs are warranted. Further studies are necessary to determine the factors associated with the development of SPM to avoid precipitating agents especially in patients with lower risk disease since these individuals should have extended survival that may be substantially shortened by the development of treatment-related SPM.

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