T(11;14) with Multiple Myeloma: Standard Risk Survival but Slow and Poor Response

Introduction:

Presence of t(11;14) on plasma cells is considered a standard-risk prognostic factor per IMWG risk-stratification. However, recent studies suggest inferior PFS and OS observed among t(11;14) patients relative to the standard-risk myeloma patients.

Methods:

This study aimed to evaluate the impact of t(11;14) in newly diagnosed multiple myeloma (NDMM) patients on treatment response rate, response kinetics, and survival based on mutually exclusive risk groups. We describe 790 patients with newly diagnosed myeloma treated with available baseline FISH data (within 90 days post-diagnosis) from January 2010 until June 2021, including 99 patients with t(11;14) alone, 58 with t(11;14) plus other high-risk cytogenetic abnormalities [t(11;14)+HR] including chromosome 1 abnormalities [C1A1, including gain/amp1q and/or del(1p)] and/or del(17p), 224 standard-risk (SR) patients without t(11;14) and 409 in the high-risk cytogenetic abnormality (HRCA) group including t(4;14), t(14;16), t(14;20), C1A1 and/or del(17p) but without t(11;14).

Results:

Our study have showed NDMM patients in the t(11;14)alone group had similar PFS (49.3 vs. 50.7 months; P= 0.392) and OS (112.4 vs. NR months; P= 0.982) as those in the SR patients, but had a significantly worse response than the SR group (t(11;14)alone vs. SR: ≥VGPR 72.9% vs. 85.2%, P= 0.011; ≥CR 50.0% vs. 66.8%, P= 0.005; MRD- 60.0% vs. 76.0%, P=0.009). Paradoxically, depth of response does not seem to be significantly associated with better survival in the t(11;14)alone group (PFS: < VGPR vs. CR, P=0.235, MRD- vs. MRD+, P= 0.159; OS: <VGPR vs. CR, P=0.256, MRD- vs. MRD+: P= 0.082). Response kinetics analyses showed that the t(11;14)alone group had a significantly slower time to response than the other subgroups (t(11;14)alone vs. SR vs. HRCA: median time to VGPR=4.93 vs. 3.01 vs. 2.63 months; P< 0.05; median time to MRD negativity= 9.19 vs. 4.25 vs. 4.27 months; P<0.001).

Conclusion:

The slow rate of response may explain the paradoxical relationship between poorer depth of response and standard risk survival outcomes, suggesting the need for individualised therapeutic strategies for this group of patients. On the other hand, t(11;14) coexistence does not provide a survival benefit for high-risk genetic patients. Patients with t(11;14) plus other high risk cytogenetic abnormalities requires early and more aggressive treatment options, such as BCL-2 inhibitors.

No relevant conflicts of interest to declare.