TY - JOUR
T1 - Autologous Stem Cell Transplantation for Patients with Multiple Myeloma with Translocation (4;14)
T2 - The MD Anderson Cancer Center Experience
AU - Pasvolsky, Oren
AU - Gaballa, Mahmoud R.
AU - Milton, Denái R.
AU - Masood, Adeel
AU - Sami, Sophiya S.
AU - Tanner, Mark R.
AU - Bashir, Qaiser
AU - Srour, Samer
AU - Saini, Neeraj
AU - Ramdial, Jeremy
AU - Nieto, Yago
AU - Tang, Guilin
AU - Lin, Pei
AU - Lee, Hans C.
AU - Patel, Krina K.
AU - Kebriaei, Partow
AU - Thomas, Sheeba K.
AU - Weber, Donna M.
AU - Orlowski, Robert Z.
AU - Shpall, Elizabeth J.
AU - Champlin, Richard E.
AU - Qazilbash, Muzaffar H.
N1 - Publisher Copyright:
© 2023 The American Society for Transplantation and Cellular Therapy
PY - 2023/4
Y1 - 2023/4
N2 - Translocation between chromosomes 4 and 14, t(4;14), has been reported in 15% of patients with multiple myeloma (MM) and is considered a high-risk cytogenetic abnormality associated with inferior outcomes. Autologous hematopoietic stem cell transplantation (auto-HCT) is standard of care for patients with high-risk MM, yet there are scarce data on post-transplantation outcomes of patients with t(4;14) MM. The aim of the present study was to evaluate outcomes of MM patients with t(4;14) who underwent auto-HCT and received contemporary anti-myeloma agents for induction and post-transplantation maintenance. We conducted a retrospective analysis of MM patients with t(4;14), detected by fluorescence in situ hybridization (FISH), who underwent auto-HCT between 2008 and 2018 at MD Anderson Cancer Center. Primary endpoints were progression-free survival (PFS) and overall survival (OS), and secondary endpoints were hematologic response and minimal residual disease (MRD) status after auto-HCT. MRD status in the bone marrow biopsy was evaluated using 8-color next-generation flow cytometry with a sensitivity of 1/10−5 cells. Seventy-nine patients were included (52% male), with a median age of 60 years (range, 32 to 78 years). Forty-four patients (56%) had an additional high-risk cytogenetic abnormality. Fifty patients (63%) achieved at least a very good partial response (≥VGPR) prior to auto-HCT and 20 (25%) had MRD-negative ≥VGPR. At the best post-transplantation evaluation, 90% had ≥VGPR and 63% had MRD-negative ≥VGPR. The median follow-up for survivors was 35.7 months (range, 7.7 to 111.6 months). For the entire cohort, median PFS and OS were 22.9 months and 60.4 months, respectively. Patients with MRD-negative ≥VGPR prior to transplantation had improved PFS and OS on both univariate analysis (UVA) and multivariate analysis (MVA) (hazard ratio [HR],.35 [95% confidence interval (CI),.16 to.76; P =.008] and.12 [95% CI,.03 to.44; P =.002], respectively). The presence of additional high-risk cytogenetic abnormalities was not associated with inferior PFS (P =.57) or OS (P =.70). Post-transplantation lenalidomide-based combinations were associated with improved OS in both UVA and MVA (HR,.14; 95% CI,.04 to.45; P =.001), while their impact on PFS was not statistically significant (P =.37). Our results consolidate t(4;14) as a high-risk abnormality associated with poor outcomes despite novel agent induction, auto-HCT, and post-transplantation maintenance. Despite some inherent study design limitations, including a relatively small cohort and heterogeneity in treatment, we observed that deeper pretransplantation response and post-transplantation maintenance with lenalidomide-based combination were associated with improved outcomes. Novel immune and cellular therapies are needed to improve the outcomes in patients with t(4;14).
AB - Translocation between chromosomes 4 and 14, t(4;14), has been reported in 15% of patients with multiple myeloma (MM) and is considered a high-risk cytogenetic abnormality associated with inferior outcomes. Autologous hematopoietic stem cell transplantation (auto-HCT) is standard of care for patients with high-risk MM, yet there are scarce data on post-transplantation outcomes of patients with t(4;14) MM. The aim of the present study was to evaluate outcomes of MM patients with t(4;14) who underwent auto-HCT and received contemporary anti-myeloma agents for induction and post-transplantation maintenance. We conducted a retrospective analysis of MM patients with t(4;14), detected by fluorescence in situ hybridization (FISH), who underwent auto-HCT between 2008 and 2018 at MD Anderson Cancer Center. Primary endpoints were progression-free survival (PFS) and overall survival (OS), and secondary endpoints were hematologic response and minimal residual disease (MRD) status after auto-HCT. MRD status in the bone marrow biopsy was evaluated using 8-color next-generation flow cytometry with a sensitivity of 1/10−5 cells. Seventy-nine patients were included (52% male), with a median age of 60 years (range, 32 to 78 years). Forty-four patients (56%) had an additional high-risk cytogenetic abnormality. Fifty patients (63%) achieved at least a very good partial response (≥VGPR) prior to auto-HCT and 20 (25%) had MRD-negative ≥VGPR. At the best post-transplantation evaluation, 90% had ≥VGPR and 63% had MRD-negative ≥VGPR. The median follow-up for survivors was 35.7 months (range, 7.7 to 111.6 months). For the entire cohort, median PFS and OS were 22.9 months and 60.4 months, respectively. Patients with MRD-negative ≥VGPR prior to transplantation had improved PFS and OS on both univariate analysis (UVA) and multivariate analysis (MVA) (hazard ratio [HR],.35 [95% confidence interval (CI),.16 to.76; P =.008] and.12 [95% CI,.03 to.44; P =.002], respectively). The presence of additional high-risk cytogenetic abnormalities was not associated with inferior PFS (P =.57) or OS (P =.70). Post-transplantation lenalidomide-based combinations were associated with improved OS in both UVA and MVA (HR,.14; 95% CI,.04 to.45; P =.001), while their impact on PFS was not statistically significant (P =.37). Our results consolidate t(4;14) as a high-risk abnormality associated with poor outcomes despite novel agent induction, auto-HCT, and post-transplantation maintenance. Despite some inherent study design limitations, including a relatively small cohort and heterogeneity in treatment, we observed that deeper pretransplantation response and post-transplantation maintenance with lenalidomide-based combination were associated with improved outcomes. Novel immune and cellular therapies are needed to improve the outcomes in patients with t(4;14).
KW - Autologous hematopoietic cell transplantation
KW - Multiple myeloma
KW - Translocation (4,14)
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U2 - 10.1016/j.jtct.2023.01.010
DO - 10.1016/j.jtct.2023.01.010
M3 - Article
C2 - 36646323
AN - SCOPUS:85150461176
SN - 2666-6367
VL - 29
SP - 260.e1-260.e6
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 4
ER -