Contributions
Abstract: EP1245
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Allogeneic stem cell transplantation (alloSCT) in multiple myeloma (MM) is considered a treatment option in relapsed MM, especially in the presence of high-risk disease as indicated by early progression post upfront autologous transplantation (ASCT) or adverse cytogenetics.
Aims
There is no standard conditioning regimen, especially in patients considered to be melphalan-refractory and data on alloSCT in relapsed MM consist of heterogenous patient populations. We aimed to study a TBI-based submyeloablative conditioing regimen in relapsed high-risk MM.
Methods
Between September 2009 and December 2017, we investigated a submyeloablative conditioning regimen consisting of 8 Gy total body irradiation (TBI) and cyclophosphamide (total 80mg/kg bodyweight) followed by alloSCT in 32 consecutive patients with early progression post upfront ASCT.
Results
90.6% of patients initially received novel agent-based induction therapy prior to ASCT. 58.3% had adverse cytogenetics (deletion17p, t(4;14), t(14;16) or gain 1q21 > 3 copies) and 79.2% had high-risk MM disease as defined by either International Staging System stage III, elevated LDH (above upper limit of the normal) or adverse cytogenetics and all patients had early disease progression (<24 months) post ASCT (median time to progression post ASCT: 300 days, range 52–664). Median lines of therapy prior to alloSCT reinduction was 1 (range 1-8) with a rate of very good partial response or better (≥VGPR) of 37.5%. Median time of hospitalization for conditioning and alloSCT was 29 days (range: 21 – 64 days). Toxicity of alloSCT during hospitalization was low and acceptable with only one early death (febrile neutropenia with multi-organ failure). Median days to engraftment of neutrophils and platelets of 14 days (range: 11 – 27 days) and 11 days (range: 8 – 34 days), respectively. Acute graft-versus-host disease (GvHD) occurred in 15 patients (20.0% ≥3 grade) and chronic GvHD in 18 patients (mild: 44.4%, moderate: 38.9%, severe: 16.7%). Response rates post alloSCT (between days 100-180) were ≥VGPR in 41.4% of patients. Maintenance therapy post alloSCT was applied in only 10.7% of patients. After a median follow-up of 76.7 months, median progression-free (PFS) and overall survival (OS) from alloSCT were 9.4 (95% CI: 5.2 – 13.7 months) and 28.8 months (95% CI: 8.0 - 49.5 months), 3- and 5-year OS rates were 50% and 30%, respectively. Non-relapse mortality (NRM) was 12.5% at 1 and 3 years (95% CIs: 4 - 27% each).
Conclusion
Our study demonstrated an acceptable toxicity profile, low NRM and a small fraction of high-risk patients achieving long-term disease control with 8 Gy TBI / cyclophosphamide conditioning prior to alloSCT in a homogenous cohort of MM with early relapse post upfront ASCT. The role of alloSCT in high-risk, relapsed MM deserves further investigation with optimized reinduction, conditioning and maintenance therapies.
Keyword(s): Allogeneic stem cell transplant, High risk, Multiple myeloma
Abstract: EP1245
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Allogeneic stem cell transplantation (alloSCT) in multiple myeloma (MM) is considered a treatment option in relapsed MM, especially in the presence of high-risk disease as indicated by early progression post upfront autologous transplantation (ASCT) or adverse cytogenetics.
Aims
There is no standard conditioning regimen, especially in patients considered to be melphalan-refractory and data on alloSCT in relapsed MM consist of heterogenous patient populations. We aimed to study a TBI-based submyeloablative conditioing regimen in relapsed high-risk MM.
Methods
Between September 2009 and December 2017, we investigated a submyeloablative conditioning regimen consisting of 8 Gy total body irradiation (TBI) and cyclophosphamide (total 80mg/kg bodyweight) followed by alloSCT in 32 consecutive patients with early progression post upfront ASCT.
Results
90.6% of patients initially received novel agent-based induction therapy prior to ASCT. 58.3% had adverse cytogenetics (deletion17p, t(4;14), t(14;16) or gain 1q21 > 3 copies) and 79.2% had high-risk MM disease as defined by either International Staging System stage III, elevated LDH (above upper limit of the normal) or adverse cytogenetics and all patients had early disease progression (<24 months) post ASCT (median time to progression post ASCT: 300 days, range 52–664). Median lines of therapy prior to alloSCT reinduction was 1 (range 1-8) with a rate of very good partial response or better (≥VGPR) of 37.5%. Median time of hospitalization for conditioning and alloSCT was 29 days (range: 21 – 64 days). Toxicity of alloSCT during hospitalization was low and acceptable with only one early death (febrile neutropenia with multi-organ failure). Median days to engraftment of neutrophils and platelets of 14 days (range: 11 – 27 days) and 11 days (range: 8 – 34 days), respectively. Acute graft-versus-host disease (GvHD) occurred in 15 patients (20.0% ≥3 grade) and chronic GvHD in 18 patients (mild: 44.4%, moderate: 38.9%, severe: 16.7%). Response rates post alloSCT (between days 100-180) were ≥VGPR in 41.4% of patients. Maintenance therapy post alloSCT was applied in only 10.7% of patients. After a median follow-up of 76.7 months, median progression-free (PFS) and overall survival (OS) from alloSCT were 9.4 (95% CI: 5.2 – 13.7 months) and 28.8 months (95% CI: 8.0 - 49.5 months), 3- and 5-year OS rates were 50% and 30%, respectively. Non-relapse mortality (NRM) was 12.5% at 1 and 3 years (95% CIs: 4 - 27% each).
Conclusion
Our study demonstrated an acceptable toxicity profile, low NRM and a small fraction of high-risk patients achieving long-term disease control with 8 Gy TBI / cyclophosphamide conditioning prior to alloSCT in a homogenous cohort of MM with early relapse post upfront ASCT. The role of alloSCT in high-risk, relapsed MM deserves further investigation with optimized reinduction, conditioning and maintenance therapies.
Keyword(s): Allogeneic stem cell transplant, High risk, Multiple myeloma