Prognostic impact of t(11;14) on PFS1 among patients with myeloma receiving triplet induction therapy.

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8064 Background: Presence of t(11;14) on plasma cells by FISH or metaphase cytogenetics 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. In the context of the ongoing trials of BCL-2 inhibitors (venetoclax) among t(11;14) relapse/refractory myeloma patients yielding response rates closer to 90%, we review the prognostic impact of t(11;14) on PFS. These results may have implications for earlier incorporation of BCL-2 inhibitors among t(11;14) myeloma patients. Methods: Among the 1000 consecutive newly diagnosed myeloma patients uniformly treated with RVD induction therapy from January 2008 until August 2016, we have information on FISH probes for t(11;14) tested for 869 patients [121 - t(11;14) and 748 – no t(11;14)]. First, we explore the frequency of IMWG defined concomitant high-risk cytogenetic characteristics [del 17p, t(4;14), t (14;16)]. Next, we create a synthetic control cohort that received maintenance, and excluded patients exhibiting high-risk features to evaluate the relative prognostication conferred by presence of t(11;14). Median follow up was 91 months. Demographic and outcomes data were collected from IRB approved myeloma database and responses were evaluated per IMWG Uniform Response Criteria. Results: Median age is 61.2 years (range 16.3-79.83). 34% of the patients are above the age of 65. Men (14.1% vs 11.7%, p = NS) and blacks had higher rates of t(11;14) (16.1% vs 11.1%, p = 0.028). 17 (14%) had concomitant high-risk features – 4 (3.3%) had t(4;14), 3 (2.5%) had t(14;16) and 11 (9.1%) had del17p. Interestingly, the rates of amplification of 1q (26.1% vs 14.9%, p = 0.002), and del13 (34.7% vs 24.4%, p = 0.015) were higher among t(11;14) patients. Compared to the synthetic cohort, the post-induction and post-transplant responses were lower for t(11;14) patients as summarized in table 1. ≥VGPR for t(11;14) vs no t(11;14) post-induction were 48.2% vs 71.5% p < 0.001 and post-transplant were 83.1% vs 92.8% p = 0.001, respectively. The median progression-free survival for the t(11;14) and non-t(11;14) groups were 61.4 months (95% confidence interval (CI), 49.13-73.67) and 82.56 months (95% CI, 70.47-94.65) months, respectively (p = 0.002). Conclusions: Even with the use of modern day induction regimens and transplant, patients with t(11;14) seem to have inferior response rates compared to the other standard-risk myelomas. The lower rates of ≥VGPR post-induction and the shorter median PFS suggests BCL-2 inhibitors such as venetoclax may be incorporated earlier in myeloma treatments to improve the outcomes of t(11;14) patients on par with the other standard-risk myeloma patients.