Impact of t(11;14) on the Outcome of Autologous Transplantation in Multiple Myeloma: A Matched-Pair Analysis

Abstract:

Background:

The translocation t(11;14)(q13;q32) is the most common chromosomal translocation in multiple myeloma (MM) with a reported frequency of 15-20%. Most, but not all, reports in the literature have identified this translocation with a relatively favorable outcome. In a smaller cohort, we had previously reported the impact of t(11;14) on the outcomes of MM patients who underwent autologous hematopoietic transplantation (auto-HCT) at our institution¹. In this study, we present an updated analysis with a larger cohort of t(11;14) patients, and compared their outcomes to a propensity-matched control group of MM patients with normal diploid cytogenetics and no high-risk abnormalities detected by Fluorescence in Situ Hybridization (FISH).

Methods and patients:

A total of 1365 MM patients underwent auto-HCT at our institution from 2007 to 2015. We identified 95 patients with t(11;14) by FISH before auto-HCT. Out of these 95 patients, 44 had t(11;14) alone, 26 had co-existent high-risk abnormalities and remaining 25 had standard-risk abnormalities. The control group included 287 MM patients with normal diploid cytogenetics and no abnormalities detected by FISH. From the above two cohorts, using a 1:1 propensity score-matched analysis without replacement, we identified matched controls for 79 patients with t(11;14). Clinical response, relapse, and progression were defined by the International Myeloma Working group criteria. The FISH technique was performed using a LSI IGH/CCND1 XT dual color, dual fusion translocation probe from Abbott Molecular, Inc. The normal cut off for IGH/MYEOV/CCND1 rearrangement using LSI IGH/CCND1 XT probe established at 95 (P<0.05) confidence level in the our Cytogenetics Laboratory is 0.4% for 1R1G2F; 1.1% for 2R2G1F; 3.4% for 3R2G; 7.4% for 2R3G and 0% for 1R3F signal patterns.

Results:

Table 1 includes the baseline characteristics of the matched doublets. Patients in both groups were well matched for age, ISS stage, serum creatinine, response to induction therapy, induction and preparative regimens, and maintenance therapy. The median follow-up time for the cohort was 48.1 months (range: 0.8-124.6). The overall response rate (CR+VGPR+PR) after auto-HCT was 77/79 (97%) and 78/79 (99%) patients in the t(11;14) and the control group, respectively (P = 1.00). Twenty eight (35%) and 37 (47%) patients achieved a CR in the t(11;14) and the control group, respectively. VGPR rate in the t(11;14) and the control group was 35 (44%) and 31 (39%), respectively. The median PFS for the t(11;14) and the control groups were 33.3 (95%CI: 25.8-not reached) and 39.7 (95%CI: 36.6-not reached) months, respectively (p = 0.24, stratified log-rank test). The median OS has not been reached for both groups (p=0.35). The 4-year PFS rates in the t(11;14) and the control groups were 42% (95%CI: 31%-57%) and 50% (95%CI: 38%-65%), respectively (Fig. A). The 4-year OS rates in the t(11;14) and the control groups were 76% (95%CI: 65%-90%) and 87% (95%CI: 79%-97%), respectively (Fig. B).

Conclusions:

On a propensity score matching analysis, multiple myeloma patients with translocation t(11;14) had similar response rates, PFS and OS to auto-HCT as standard-risk patients with normal cytogenetics or FISH studies.

References:

1. Qazilbash MH et.al. Impact of t(11;14)(q13;q32) on the outcome of autologous hematopoietic cell transplantation in multiple myeloma. Biol Bone Marrow Transplant 2013 Aug;19(8):1227-32.

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