Outcomes of Myeloma Patients with t(11;14) Receiving Lenalidomide, Bortezomib, and Dexamethasone (RVD) Induction Therapy
Authors: Kaufman Jonathan L , Joseph Nisha , Gupta Vikas A. , Gleason Charise , Hofmeister Craig C , Heffner Leonard , Dhodapkar Madhav V , Lonial Sagar , Boise Lawrence H. , Nooka Ajay K 
Published: October 2019

Abstract
Background: In the cytogenetic risk-stratification of myeloma, identification of t(11;14) on plasma cells has long been regarded as a standard risk prognostic factor. More recently, there have been reports of inferior PFS and OS relative to the standard risk myeloma patients. These results carry significance in the current day, as an ongoing phase I trial of Bcl-2 inhibitor (venetoclax) reported an ORR of 40% among myeloma patients with t(11;14) leading way for individualized therapeutic approach for myeloma. In this context, we evaluated the clinical outcomes of t(11;14) myeloma patients receiving uniform modern day induction therapies to evaluate the prognostic implication of this translocation.
Methods: Of the 1000 consecutive newly diagnosed myeloma patients treated with RVD induction therapy per Richardson et al (Blood 2010) from July 2005 until August 2016, we have FISH probes for t(11;14) tested in 867 patients. Among these patients, we identified 122 patients with t(11;14). Excluding 247 patients that had del 17p, t(4;14), t (14;16) and complex karyotype on metaphase cytogenetics, we have identified 527 patients that formed the control group of standard risk myeloma. Demographic and outcomes data for the patients were collected from our IRB approved myeloma database and responses were evaluated per IMWG Uniform Response Criteria.
Results: Median age of the patients is 61 years (range 16-83). 32% of the patients are above the age of 66. Other patient characteristics include: M/F 56%/44%; W/AA 62%/36%; ISS I/II/III 48%/30%/22%; Isotype IgG/IgA/FLC 60%/18%/19%. Response rates are summarized in table 1. Post induction responses ≥VGPR are lower for t(11;14) compared with non-t(11;14): 49.5% vs 76.3% p<0.001 and similarly best VGPR for t(11;14) vs non-t(11;14): 76.3% vs 91.4% p=0.001. The median progression-free survival for the t(11;14) and non-t(11;14) groups were 51 months (95% confidence interval (CI), 30.628-71.372) and 75 months (95% CI, 57.882-92.118) months, respectively (P<0.001), at a median follow up of 39 months. This difference is more pronounced among patients not receiving maintenance therapy (29 vs 62 months, p=0.001). The median overall survival (OS) for t(11;14), and non-(11;14) groups were not reached at a median follow up of 38 months.
Conclusions: Even with the use of modern day induction regimens, patients with t(11;14) have inferior outcomes compared to the other patients standard risk myeloma. The lower rates of ≥VGPR post-induction and the shorter median PFS suggests more novel regimens such as venetoclax should be studied earlier in the course to improve the outcomes of t(11;14) patients on par with the other standard risk myeloma patients.

Disclosures
Kaufman: Janssen: Consultancy; Abbvie: Consultancy; Karyopharm: Other: data monitoring committee; Roche: Consultancy; BMS: Consultancy. Hofmeister:Adaptive biotechnologies: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Heffner:ADC Therapeutics: Research Funding; Pharmacyclics: Research Funding; Kite Pharma: Research Funding; Genentech: Research Funding. Lonial:Amgen: Research Funding. Boise:AstraZeneca: Honoraria; Abbvie: Consultancy. Nooka:GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive technologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees.