P-178: Impact of t(11;14) according to induction regimen in newly diagnosed transplant-eligible multiple myeloma patients: long term follow-up of GEM05MENOS65 and GEM2012 PETHEMA/GEM studies

Abstract

<h3>Background</h3> t(11;14) is the most frequently IgH rearrengement in newly diagnosed multiple myeloma (NDMM) with a 15-20% prevalence and is considered a standard-risk cytogenetic abnormality (SR). However, t(11;14) is controversial since recent reports describe inferior outcomes in contrast to other SR patients. We analyze the long-term outcome of t(11;14) compared to the remaining SR population in transplant-eligible patients included in GEM05MENOS65 and GEM2012 spanish trials for NDMM. <h3>Methods</h3> 386 patients included in GEM05MENOS65 trial were randomized to receive induction with 6 cycles of thalidomide and dexamethasone (TD) vs. 6 cycles of VTD vs. 4 cycles of alternating chemotherapy (VBMCP/VBAD) plus 2 cycles of bortezomib (VBMCP/VBAD/B). 458 patients included in GEM2012 trial received induction with 6 cycles of VRD. <h3>Results</h3> From a total of 414 SR patients, 84 (20%) were positive for t(11;14) and 328 (80%) were SR non-t(11;14). There were no differences in baseline characteristics among groups. In the VBMCP/VBAD/B arm, there were no significant differences in ORR or CR rate after induction between patients with t(11;14) or other SR (ORR 93 vs. 85%, p=0.4; CR 21 vs. 16%, p=0.6). However, patients with t(11;14) treated with VTD had lower ORR and CR rates after induction than SR patients (ORR 85 vs. 97%, p=0.04; CR 15 vs. 38%, p=0.1). Patients with t(11;14) treated with TD had lower ORR and CR rates although the differences were not statistically significant (ORR 63 vs. 78%, p=0.2, CR 5 vs. 11%, p=0.4). In the VRD arm, patients with t(11;14) had similar ORR and CR compared to other SR (ORR 87 vs. 89%, p=0.8; CR 24 vs. 32%, p=0.3). With a median follow-up of 54.2 months, no differences in median PFS were observed in the VBMCP/VBAD/B arm (44 vs. 46 months; p=0.7). However, shorter PFS was observed in patients with t(11;14) in the TD (30 vs. 46 months; p=0.03) and VTD arms (28 vs. 72 months; p=0.003). With VRD, median PFS was not reached for patients with t(11;14) and SR non-t(11;14) (p=0.8). Among patients with t(11;14), VTD showed shorter median PFS compared to VRD (28 months vs. not reached, p<0.01). Patients with t(11;14) treated in the VBMCP/VBAD/B arm showed shorter median OS than SR patients (66 months vs. not reached; p=0.03). In contrast, median OS was not reached in patients with t(11;14) or SR in neither TD, VTD and VRD arms. <h3>Conclusion</h3> Thalidomide-based induction regimens (VTD/TD) are suboptimal in patients with t(11;14) concerning response rates and PFS than SR patients, although this does not impact on OS. In contrast, VRD showed similar ORR and PFS in patients with t(11;14) and SR. Despite this is a non-randomized comparison, VRD appears to be more effective than VTD in this subset of patients. Patients with t(11;14) receiving induction with chemotherapy have the same response and PFS than SR patients but display a shorter OS. These results should be confirmed in larger series.