Outcome Of t(4;14) In Multiple Myeloma - Princess Margaret Cancer Centre Experience Over The Last 10 Years
Authors: Farooki Sophia , Maganti Manjula , Reece Donna E , Masih-Khan Esther , Jimenez-Zepeda Victor H , Trudel Suzanne , Chen Christine I. , Tiedemann Rodger E. , Kukreti Vishal 
Published: October 2019

Abstract
Translocation (4;14) is identified by FISH cytogenetics in approximately 15% of myeloma patients (pts). Pts with this translocation have a poor outcome characterized by initial response to induction chemotherapy but followed by rapid relapse and resistance to alkylating agents. Recent studies have suggested that novel agents such as bortezomib may improve both event-free survival and overall survival (OS). We reviewed the outcome of 74 consecutive myeloma pts with t(4;14) managed at Princess Margaret Cancer Centre between October 2002 and July 2012. Our goal was to evaluate the impact of specific pts' characteristics on OS and to assess outcome according to treatments received. Clinical characteristics at time of diagnosis for the 74 myeloma pts with t(4;14) are presented in table 1. The average age was 57 years (range 31-82 years) and 58% were male. Pts received a median of 2 lines of therapy (range 1-6). Of the 69 pts requiring treatment, 46% of pts received one year of bortezomib as part of the Canadian t(4;14) clinical trial, 32% of pts were treated with novel agents including bortezomib (given for an average of 4 months) and lenalidomide, 22% of pts received conventional treatment such as dexamethasone alone, thalidomide and/or melphalan. 20 pts underwent autologous stem cell transplantation (ASCT) as part of their first line treatment; 16 were single ASCT, 4 were tandem ASCT. The overall response rate to induction chemotherapy was 70%, with 60% complete response/very good partial response and 10% partial response. The median OS was 5 years and 3 year OS was 66%. Presence of p53 significantly decreased the 3 year OS (71% vs 29% for absence and presence of p53, respectively, log-rank p value=0.0017). Median follow-up was 2.43 years (range: 0.24-11.81 years). There was no significant difference in OS based on the type of first line treatment received. The 3 year OS was 69% for pts enrolled in the t(4;14) clinical trial, 65% for pts who received novel agents and 53% for pts who received conventional treatment (log-rank p value=0.33). In a multivariable analysis looking at pts' initial characteristics, p53 deletion, LDH, bone lesions and age at diagnosis were found to be significant predictors of overall survival while ISS staging and immunoglobulin isotype were not found to be significant for overall survival. In conclusion, in our retrospective single institution study, the median OS for pts with t(4;14) was 5 years. Older age, addition of p53 deletion, high LDH and presence of bone disease predicted a worse OS. Although the lack of significant difference in OS based on the type of first line treatment received may be due to the limited number of pts in our study, there was a trend towards improvement in OS for pts that received a bortezomib containing regimen versus those who received conventional agents. While the median OS for pts with t(4;14) in our study has increased compared to historical controls, new therapeutic options are still needed to further improve the outcome in this subset of pts3.
3 Keats JJ et al. In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression. Blood. 2003 Feb 15;101(4):1520-9.Table 1Clinical characteristics for the 74 myeloma pts with t(4;14)Clinical characteristicsAverageRange%Hemoglobin (g/L)10051-157Creatinine (μmol/L)13933-796Calcium (mmol/L)2.41.89-3.84B2-microglobulin (mg/L)4.51.58-20.25Albumin (g/L)3518-46ISS stage 145%ISS stage 236%ISS stage 319%Presence of bone lesions68%Mean % of nuclei positive for t(4;14)3%-71.5%25%Presence of del 13q/monosomy 13 by FISH77%Presence of del 17p by FISH10%

Disclosures:
Reece: Celgene: Honoraria, Research Funding; Jansen: Honoraria, Research Funding; Onyx: Honoraria; Novartis: Honoraria; BMS: Research Funding; Merk: Honoraria, Research Funding; Millennium: Research Funding.