PF589 MULTIPLE HIGH‐RISK CYTOGENETIC ABERRATIONS CONFER A PROGRESSIVELY NEGATIVE IMPACT ON SURVIVALS OF NEWLY DIAGNOSED MYELOMA PATIENTS
Authors: Mao X.‐H. , An G. , Xu Y. , Yan Y. , Liu J. , Fan H. , Sui W. , Deng S. , Li Z. , Fu M. , Wang T. , Yi S. , Wang Q. , Liu H. , Xiong W. , Zou D. , Qiu L. 
Published: June 2019

Background:

Cytogenetic aberration detected by fluorescence in situ hybridization is one of the most important prognostic factors for multiple myeloma (MM). Identifying patients with high risk aberrations (HRA) is critical for initial risk stratification as well as follow‐up treatment. Although specific HRA has been well discussed, cumulative impact of multiple HRA is still unclear. Also, the limited published reports on this issue were almost conducted in the context of traditional chemotherapy, with incomplete FISH detections.

Aims:

Based on our comprehensive FISH panels and uniformly treated cohort, we aimed to depict patients’ clinical characteristics as well as the impact of multiple high‐risk aberrations on their survival in the era of novel agents.

Methods:

In our prospective non‐randomized clinical study (BDH 2008/02) study, 573 cases of NDMM with a comprehensive FISH panel were evaluated. OS and PFS for patients were compared across different number of HRA group, stratified analysis for age, disease stage as well as initial treatment were also conducted.

Results:

In multivariate analysis, we found that,of all these parameters, age≥65 years old (HR = 1.64, 95% CI 1.19–2.28, p = 0.003), LDH level ≥220 U/L (HR = 1.58, 95% CI 1.07–2.32, p = 0.02), ISS 3 stage (HR = 1.59, 95% CI 1.13–2.26, p = 0.009), del(17p) (HR = 1.68, 95% CI 1.03–2.73, p = 0.036), amp(1q21) (HR = 1.72, 95% CI 1.26–2.34, p = 0.001), and adverse IgH translocation (t(4;14) or t(14;16)) (HR = 1.65, 95% CI 1.17–2.34, p = 0.005) were statistically independent prognostic factors for shortened OS; while taking autologous stem cell transplant (ASCT)(HR = 0.37, 95% CI 0.22–0.63, p = 0.000) profoundly prolonged OS for patients.

Accordingly, HRA was defined by the presence of t(4;14), t(14;16),1q21 gain or del(17p). For all 573 cases, number of patients harboring 0–3 HRA were 236(41.2%), 236(41.2%), 94(16.4%) and 7(1.2%), respectively. When occurred in isolation, every HRA conferred a similar and modulate impact on OS [for del(17p), amp(1q21), and t(4;14)/ t(14;16), overall survival (OS) was 50.1, 63.9 and 64.3 months, respectively, with p value across three subgroup of 0.33]. OS of patients with 0–3 HRA was NR (Not Reached), 62.1, 38.8, and 22.9 months, respectively (with p value across three subgroup of 0.000). A clear progressive association between the accumulation of HRA and impairment of survival was observed. In risk stratification analysis by age, serum LDH level, DS stage, ISS stage, induction therapy and transplantation, the cumulative cytogenetic model remained its prognostic value in differentiating patients into three risk group: low‐risk group was defined as patients with 0 HRA; intermediate‐risk group was defined as patients with 1 HRA; and patients with ≥2 HRA was assigned to the high‐risk group. Specifically, ASCT remarkably improved survival of patients across different groups, especially those with one or more HRA.

Summary/Conclusion:

Taken together, our study showed that while isolated adverse IgH (t(4;14) or t(14;16)), del(17p) and 1q21 gain carried similar negative impact on survival, concurrent multiple HRA progressively impaired overall survival of MM patients. Patients with two or more HRA were considered as high‐risk group, and transplantation may attenuate their negative prognosis.

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