P-356: Prognostic impact of t(11;14) in newly diagnosed patients with multiple myeloma

Introduction:
Translocation t(11;14) has emerged as a crucial genetic aberration and is one of the most common primary translocations in multiple myeloma (MM). One of the key features linked with t(11;14) is the BCL2 dependency, which is a druggable target with BCL2 inhibitors. In the era of the novel anti-myeloma agents, the exact prognostic role of t(11;14) remains to be determined.

Methods:
We analyzed data from 1011 consecutive patients with newly diagnosed MM (NDMM), who were diagnosed and treated in our department, from 1997 to 2023. All were tested for t(11;14) at diagnosis using standard fluorescent in-situ hybridization in CD138+ selected cells. Positivity was defined as at least 20% of clonal cells harboring t(11;14). The presence of +1q21, t(4;14), t(14;16), del(17p), del(13q), were also determined by FISH.

Results:
At baseline, 89 out of 1011 patients (8.8%) had the t(11;14), whereas 922 (91.2%) were negative. The median age was 68 years for both subgroups (range 37-88 and 34-93, respectively), whereas 42 (47%) and 502 (54%) were males (p=0.35), respectively.

Overall, patients with t(11;14) did not have a statistically significant difference in progression-free survival (PFS) compared with those who did not had t(11;14) [hazard ratio (HR) 1.25, 95% confidence interval (CI) 0.92 – 1.70, p=0.15]. Patients with no cytogenetic abnormalities at diagnosis had superior PFS compared with those who were positive for t(11;14) (HR 1.41, p=0.04) or any other cytogenetic aberration (HR 1.39, p=0.001). Interestingly, those with isolated positivity for t(11;14) did not have a statistically significant difference in PFS compared with those without any abnormalities (HR 1.28, 95%CI: 0.81-2.03, p=0.282). However, patients with t(11;14) and at least another cytogenetic abnormality had inferior PFS (HR 1.38, p=0.001). More specifically, those with t(11;14) and del17p (HR 3.74, 95%CI: 1.53-9.17, p=0.004) and those with t(11;14) and 1q21 amplification/addition (HR 1.67, 95%CI: 1.00-2.78, p=0.05) had particularly dismal outcomes.

Similarly, there was no statistically significant difference in overall survival (OS) between patients with and without t(11;14) (HR 1.31, 95%CI: 0.86-2.00, p=0.21). However, patients who had at least an additional cytogenetic abnormality had inferior OS (HR 1.68, p< 0.001). Furthermore, patients with t(11;14) had inferior OS compared with those without any aberrations (HR 1.62, 95%CI: 1.03-2.55, p=0.04). Interestingly, patients with isolated t(11;14) did not demonstrate inferior OS compared with those without any abnormalities (HR 0.61, 95%CI: 0.22-1.67, p=0.33). However, the co-presence of del17p (HR 6.03, 95%CI 2.20-16.52, p< 0.001) or 1q21 amplification/addition (HR 2.51, 95%CI: 1.30-4.86, p=0.006) with t(11;14) had a detrimental impact on OS.

Conclusions:
Isolated t(11;14) in patients with NDMM does not seem to be a marker of adverse prognosis, whereas the presence of other high-risk cytogenetic abnormalities confer dismal outcomes.