Contributions
Abstract: EP1021
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
t(11;14) is the most frequently IgH rearrangement in multiple myeloma (MM) 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.
Aims
To analyze the long-term outcome of t(11;14) compared with the remaining SR population in transplant-eligible (TE) patients included in the GEM05MENOS65 study.
Methods
From April 2006 to August 2009, 386 TE patients with newly diagnosed symptomatic MM were randomized to receive three induction regimens: six 4-week cycles of TD (thalidomide 200 mg daily; dexamethasone 40 mg on days 1-4 and 9-12) vs. six 4-week cycles of VTD (TD at identical doses plus iv bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11) vs. combination chemotherapy plus bortezomib (4 cycles of alternating VBMCP and VBAD chemotherapy followed by two cycles of iv bortezomib). All patients were planned to undergo autologous stem cell transplant (ASCT) with MEL-200 followed by maintenance therapy with thalidomide/bortezomib vs. thalidomide vs. alfa-2b-interferon for 3 years.
Results
A total of 53 (16%) patients were positive for t(11;14) but 7 patients harboring concomitant high-risk abnormalities were excluded. SR excluding t(11;14) were found in 215 (66%) patients. There were no differences in baseline characteristics among groups. In the overall series, there were no differences in overall response rate (ORR) after induction between patients with t(11;14) compared to SR (78 vs. 87%, p=0.1). However, the ≥VGPR and MRD negativity rates were lower in patients with t(11;14) (17 vs. 33%; p=0.03 and 6 vs. 33%; p=0.002). 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 SR. 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 overall series, on an intention-to-treat basis, the ORR after ASCT (65% vs 76%, p=0.1) as well as the CR and MRD negativity rates were lower for patients with t(11;14) (CR 28 vs. 45%; p=0.04, MRD negative 20 vs. 42%; p=0.01).
With a median follow-up of 63.4 months, median progression free survival (PFS) in the overall series was shorter for patients with t(11;14) (30 vs. 54 months; p=0.004). 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) (Figure 1). In the overall series, there were no differences in the overall survival (OS) between t(11;14) and SR patients. However, 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 both, TD and VTD arms.
Conclusion
In our study, bortezomib and 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. 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.
Keyword(s): Cytogenetic abnormalities, Multiple myeloma, Survival
Abstract: EP1021
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
t(11;14) is the most frequently IgH rearrangement in multiple myeloma (MM) 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.
Aims
To analyze the long-term outcome of t(11;14) compared with the remaining SR population in transplant-eligible (TE) patients included in the GEM05MENOS65 study.
Methods
From April 2006 to August 2009, 386 TE patients with newly diagnosed symptomatic MM were randomized to receive three induction regimens: six 4-week cycles of TD (thalidomide 200 mg daily; dexamethasone 40 mg on days 1-4 and 9-12) vs. six 4-week cycles of VTD (TD at identical doses plus iv bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11) vs. combination chemotherapy plus bortezomib (4 cycles of alternating VBMCP and VBAD chemotherapy followed by two cycles of iv bortezomib). All patients were planned to undergo autologous stem cell transplant (ASCT) with MEL-200 followed by maintenance therapy with thalidomide/bortezomib vs. thalidomide vs. alfa-2b-interferon for 3 years.
Results
A total of 53 (16%) patients were positive for t(11;14) but 7 patients harboring concomitant high-risk abnormalities were excluded. SR excluding t(11;14) were found in 215 (66%) patients. There were no differences in baseline characteristics among groups. In the overall series, there were no differences in overall response rate (ORR) after induction between patients with t(11;14) compared to SR (78 vs. 87%, p=0.1). However, the ≥VGPR and MRD negativity rates were lower in patients with t(11;14) (17 vs. 33%; p=0.03 and 6 vs. 33%; p=0.002). 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 SR. 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 overall series, on an intention-to-treat basis, the ORR after ASCT (65% vs 76%, p=0.1) as well as the CR and MRD negativity rates were lower for patients with t(11;14) (CR 28 vs. 45%; p=0.04, MRD negative 20 vs. 42%; p=0.01).
With a median follow-up of 63.4 months, median progression free survival (PFS) in the overall series was shorter for patients with t(11;14) (30 vs. 54 months; p=0.004). 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) (Figure 1). In the overall series, there were no differences in the overall survival (OS) between t(11;14) and SR patients. However, 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 both, TD and VTD arms.
Conclusion
In our study, bortezomib and 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. 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.
Keyword(s): Cytogenetic abnormalities, Multiple myeloma, Survival