Prognostic Impact of T(11;14) in Newly Diagnosed Patients with Multiple Myeloma in the Era of Modern Treatments

Background

Translocation t(11;14) has been recognized as a significant genetic aberration and is among the most prevalent primary translocations in multiple myeloma (MM). A notable characteristic associated with t(11;14) is BCL2 dependency, making it a druggable target with BCL2 inhibitors. Despite advancements in novel anti-myeloma agents, the precise prognostic significance of t(11;14) remains unclear.

Methods

We analyzed data from 1,007 consecutive patients with newly diagnosed multiple myeloma (NDMM) who were diagnosed and treated in our department between 1997 and 2024. At diagnosis, all patients were tested for t(11;14) using standard fluorescent in-situ hybridization (FISH) in CD138+ selected cells, with positivity defined as at least 20% of clonal cells harboring the translocation. Additionally, the presence of +1q21, t(4;14), t(14;16), del(17p), and del(13q) was also determined by FISH.

Results

At baseline, 70 out of 1,007 patients (6.9%) had t(11;14), while 937 (93.1%) did not. The median age was 68 years for both groups (ranging from 32 to 88 years and 33 to 93 years, respectively). In terms of gender distribution, 31 patients (44.3%) with t(11;14) and 507 patients (50.3%) without the translocation were males (p=0.15).

Overall, there was no statistically significant difference in progression-free survival (PFS) between patients with t(11;14) and those without it [hazard ratio (HR) 1.24, 95% confidence interval (CI): 0.85 - 1.81, p=0.26]. Patients with no cytogenetic abnormalities at diagnosis had superior PFS compared to those with t(11;14) (HR 1.52, p=0.04) or any other aberration (HR 1.53, p<0.001).

Interestingly, patients with isolated t(11;14) did not show a statistically significant difference in PFS compared to those without any cytogenetic abnormalities [hazard ratio (HR) 1.16, 95% confidence interval (CI): 0.69-1.93, p=0.58]. However, patients with t(11;14) who also had at least one other cytogenetic abnormality experienced worse PFS [HR 1.95, p=0.02]. Specifically, those with t(11;14) and del(17p) had notably poorer outcomes [HR 3.51, 95% CI: 1.45-8.51, p=0.005], as did those with t(11;14) and del(13q) [HR 4.32, 95% CI: 1.38-13.51, p=0.01].

Overall survival (OS) did not differ significantly between patients with t(11;14) and those without it [HR 1.22, 95% confidence interval (CI): 0.73-2.06, p=0.45]. However, patients with at least one additional cytogenetic abnormality had worse OS [HR 2.57, p=0.005]. Conversely, patients with t(11;14) did not show inferior OS compared to those without any cytogenetic aberrations [HR 1.62, 95% CI: 0.93-2.81, p=0.09]. Notably, patients with isolated t(11;14) had similar OS to those without any abnormalities [HR 0.89, 95% CI: 0.39-2.05, p=0.78]. However, the presence of del(13q) [HR 4.20, 95% CI: 1.04-17.01, p=0.04] or del(17p) [HR 4.00, 95% CI: 1.49-10.75, p=0.006] in addition to t(11;14) was associated with significantly worse OS.

Conclusion

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

Ntanasis-Stathopoulos:Janssen-Cilag: Honoraria; AstraZeneca: Honoraria; Cellectar Biosciences: Research Funding. Terpos:EUSA Pharma: Honoraria, Other: Travel expenses; Pfizer: Honoraria; BMS: Honoraria; AstraZeneca: Honoraria, Other: Travel expenses; Menarini/Stemline: Honoraria; GSK: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Other: Travel expenses, Research Funding; Sanofi: Honoraria, Other: Travel expenses, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Novartis: Honoraria; Antengene: Honoraria, Research Funding; Swixx: Honoraria. Fotiou:Sanofi: Honoraria; Janssen: Honoraria. Migkou:Janssen Cilag: Honoraria; GlaxoSmithKline: Honoraria. Kastritis:Janssen-Cilag: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Sanofi: Honoraria. Dimopoulos:JANSSEN: Honoraria; BMS: Honoraria; GSK: Honoraria; TAKEDA: Honoraria; MENARINI: Honoraria; REGENERON: Honoraria; SANOFI: Honoraria; AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees; BEIGENE: Honoraria; SWIXX: Honoraria; ASTRA ZENECA: Honoraria. Gavriatopoulou:Genesis Pharma: Honoraria; Amgen: Consultancy; Beigene: Research Funding; AbbVie: Honoraria; BMS: Research Funding; Cellectar Biosciences: Research Funding; GSK: Consultancy, Honoraria; Integris: Honoraria; Takeda: Consultancy, Honoraria; Swixx: Honoraria; Janssen Cilag: Honoraria; Karyopharm: Consultancy.