Real-World Outcomes In Myeloma Patients With t (11;14): A Matched Comparison Using the Canadian Myeloma Research Group National Clinical Database

BACKGROUND: In multiple myeloma, t(11;14) confers a unique biology including a lymphoplasmacytic phenotype and an association with plasma cell leukemia. Some studies report a favourable while others a worse prognosis, compared to non-t(11;14) cases. Dependence of t(11;14) cells on the BCL2 pathway offers a potential therapeutic target. METHODS: We performed a matched comparison of real-world outcomes in patients with and without t(11;14) as a benchmark for future therapy targeting BCL2. A retrospective observational study was conducted using the Canadian Myeloma Research Group database between 2004-2022. FISH and karyotype studies were used to identify which patients carried the t(11;14) versus those who did not. Those found to harbour the t(11;14) were matched one-to-one with a non-t(11;14) cohort based on age at line 1 of therapy, gender, year of diagnosis and history of autologous stem cell transplant. RESULTS: Compared with non-t(11;14), those with t(11;14) had similar PFS during line 1 (44 (95%CI: 32-51) months vs. 44 (95%CI: 36-65) months), but shorter PFS in line 2 (18 (95% CI: 11-22) months vs. 32 (95%CI: 23-49) months) resulting in a shorter PFS2 (55 (95%CI: 45-87 months vs. 83 (95%CI: 74-115) months). CONCLUSIONS: Although not yet translating into a worse OS, this merits longer follow up. This suggests the need for optimal treatment choice and sequencing at relapse within this unique cytogenetic group. Our large, matched comparison in real-world t(11;14) myeloma serves as an important benchmark for studies looking at targeted BCL2 inhibitors in these patients.