Prognostic Value of t(11;14)(q13;32) in Newly Diagnosed Myeloma Patients in Novel Agent Era; Matched-Pair Analysis

Introduction. Multiple myeloma (MM) with t(11;14)(q13;32) is one of the unique subtypes of MM, which is characterized by the consequent upregulation of cyclin D1, lymphoplasmacytic morphology, elevated levels of the antiapoptotic protein BCL-2, and low CD38 expression. In addition, venetoclax has been shown to be effective in MM with t(11;14). In the current era of novel agent, t(11;14) is considered as a standard risk while its prognostic impact is incompletely understood. To clarify the characteristics and the progression of MM with t(11;14), we analyzed our cohort of MM patients over the last 14 years.

Methods. We retrospectively evaluated 322 patients who were diagnosed as MM at Kameda medical center from April 2008 to December 2022 and performed iFISH analysis all of t(11;14), t(4;14), t(14;16), and del17p. We divided our cohort into three groups; t(11;14) group, non-t(11;14) group with high-risk cytogenetic abnormality (HRCA group), and non-t(11;14) group without HRCA (non-HRCA group). t(4;14), t(14;16), and del17p were classified into the HRCA group. For accurate survival comparison, we performed matched-pair retrospective analysis. After we excluded 8 patients having both t(11;14) and HRCA, patients data were matched for age (<75 vs ≥75 years), the international staging system (ISS) stage (l vs ll or lll), prior ASCT, and prior one or more novel agents (daratumumab, isatuximab, carfilzomib, and/or pomalidomide). Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method and analyzed with Cox proportional hazards model. Multivariate analyses were performed to evaluate prognostic factors in the t(11;14) cohort.

Results. Of 322 patients, 86 patients had t(11;14) (26.7%). The median ages were 72 years, 75 years, and 68.5 years in the t(11;14) group, the non-HRCA group, and the HRCA group respectively. In the t(11;14) group, percentage of serum circulating plasma cells (cPC) were higher than in the non-HRCA group (median [‰], 1.3 vs 0.43) yet lower than in the HRCA group (median [‰], vs 2.6). The incidence of co-expression of 1q gain was notably lower (21.5%) in comparison to the non-HRCA group (37.5%) and the HRCA group (61.7%) (p<.001). In terms of treatments, many patients received novel agents, with 49.7%, 35.7%, and 40.0% receiving anti-CD38moAb, carfilzomib, and pomalidomide, respectively. The proportions receiving one or more novel agents in these groups were 75.8%, 64.0%, and 59.8%, respectively. The proportions of patients undergoing ASCT were 37.1%, 31.4% and 27.6% in the HRCA, t(11;14) and non-HRCA groups, respectively.

With a median follow-up of 44.7 months for the entire cohort, the median PFS was 39.0 months (95% CI, 35-78), 61.0 months (95% CI, 40-84), and 37.0 months (95% CI, 22-44) in the t(11;14) group, the non-HRCA group, and the HRCA group, respectively. The median OS was 59 months (95% CI, 50-NA), 108 months (95% CI, 74-NA), and 92.0 months (95% CI, 65-99) in the same sequence. No statistical differences were seen in these survival analyses.

Next, we conducted matched-pair analysis. In the matched-t(11;14) group (n=66) and the matched-non-HRCA group (n=112), median OS was 112 months and 56.0 months (HR, 1.66; 95% CI, 1.06-2.6; p=.026). In the matched-t(11;14) group (n=56) and the matched-HRCA group (n=56), median OS was 54 months and 84 months (HR, 1.04 ;95% CI, 0.61-1.77 ;p=0.89). Median OS in the matched-t(11;14) group was only half of that in the matched-non-HRCA group, and this difference was statistically significant. Furthermore, median OS in the matched-t(11;14) group was shorter compared to that of the matched-HRCA group, although there was no statistically difference.

Finally, we performed multivariate analysis in the entire MM with t(11;14) cohort (n=86). For PFS, the multivariate analysis including variables such as ISS stage(≥ll), cPC(≧1.0‰), gain 1q, and del17p, identified cPC as statistically significant (HR, 3.11; 95% CI, 1.10-8.79; p=0.033). No statistically significant factors were found for OS.

Conclusion. In our analysis, median PFS was the longest of the non-HRCA group, followed by the t(11;14) group, and then the HRCA group. Furthermore, our matched-pair analysis regarding OS showed worse outcomes of patients with t(11;14) compared to those without HRCA in the novel agents era. There is a need to further explore optimal therapeutic strategies and management approaches for MM with t(11;14).