Contributions
Abstract: PB1687
Type: Publication Only
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Melphalan at a dose of 200mg/m2 is considered the standard autograft dose in patients with multiple myeloma without major co-morbidity. This was formulated in early years before the era of novel agent induction and maintenance. Considering the deeper remission achieved by novel agents and prevailing refractory gram negative sepsis in most Indian setups.
Aims
We compared 140mg/m2 (MEL140) vs 200mg/m2(MEL200) of Melphalan in Indian myeloma patients who achieved a complete remission before transplant without having any major co-morbidity.
Methods
We analyzed myeloma autograft patients from September 2014 to February 2018. 49 patients received MEL200 and 51 patients received MEL140. These patients were clinically randomized. Diabetes on oral medications was randomized equally on both sides. The median age of patients in MEL200 was 52 years and MEL140 was 53.6 years. There were 60% and 55% males in MEL200 vs MEL140 respectively. ISS-III patients were 48% and 49% in MEL200 vs MEL140 respectively. The standard induction regimen was three to four cycles of RvD chemotherapy. Around 16% patients in MEL140 group had a creatinine clearance between 30-50ml/min. The mobilization regimen followed was 5 days of GCSF based mobilization. The stem cell cut-off was kept to a minimum of 2 x 106/CD34+ve cells/kg bodyweight.
Results
In outcome analysis, there was no transplant related mortality in both groups. The mean day of engraftment was around Day +9 in MEL140 vs Day +11 in MEL200. The rate of Gram Negative Bacilli sepsis was around 14% in MEL140 vs 27% in Mel200 (p 0.02). This reflected in use of high end antibiotics like Colistin and Fosfomycin in such patients and there was a delay in engraftment which may have been confounded by sepsis. The median progression free survival was 26.1 months in MEL200and 27.2 months in MEL140 group. The cumulative incidence of relapse at 3 years was not significantly different between the Mel200 (36.3%) and Mel140 (37.9%) groups. The adjusted HR for relapse was 0.98. Subgroup analysis suggests that in overall survival, progression-free survival, and cumulative incidence of relapse there was no significant advantage associated with melphalan 200 mg/m2.
We formulated to compare a lower dose melphalan to prevent a stormy post-transplant course and prevent patients succumbing to sepsis. This may not be an issue in western countries where gram negative sepsis rates are lower. The biggest worry for us is not to compromise the myeloma outcome due to lower doses of Melphalan in fit patients who achieve complete remission. This study concluded that there is not much of a difference in overall survival, Progression free survival and cumulative incidence of relapse at three years among MEL200 vs MEL140.
Conclusion
We conclude that Melphalan autograft at a dose 140mg/m2 can achieve comparable responses to 200mg/m2 in Indian myeloma patients who are taken to transplant post complete remission. We need a bigger multicentric study and a longer follow up to recommend MEL140 as standard of care in Indian setting.
Keyword(s): Melphalan, Myeloma, Transplant
Abstract: PB1687
Type: Publication Only
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Melphalan at a dose of 200mg/m2 is considered the standard autograft dose in patients with multiple myeloma without major co-morbidity. This was formulated in early years before the era of novel agent induction and maintenance. Considering the deeper remission achieved by novel agents and prevailing refractory gram negative sepsis in most Indian setups.
Aims
We compared 140mg/m2 (MEL140) vs 200mg/m2(MEL200) of Melphalan in Indian myeloma patients who achieved a complete remission before transplant without having any major co-morbidity.
Methods
We analyzed myeloma autograft patients from September 2014 to February 2018. 49 patients received MEL200 and 51 patients received MEL140. These patients were clinically randomized. Diabetes on oral medications was randomized equally on both sides. The median age of patients in MEL200 was 52 years and MEL140 was 53.6 years. There were 60% and 55% males in MEL200 vs MEL140 respectively. ISS-III patients were 48% and 49% in MEL200 vs MEL140 respectively. The standard induction regimen was three to four cycles of RvD chemotherapy. Around 16% patients in MEL140 group had a creatinine clearance between 30-50ml/min. The mobilization regimen followed was 5 days of GCSF based mobilization. The stem cell cut-off was kept to a minimum of 2 x 106/CD34+ve cells/kg bodyweight.
Results
In outcome analysis, there was no transplant related mortality in both groups. The mean day of engraftment was around Day +9 in MEL140 vs Day +11 in MEL200. The rate of Gram Negative Bacilli sepsis was around 14% in MEL140 vs 27% in Mel200 (p 0.02). This reflected in use of high end antibiotics like Colistin and Fosfomycin in such patients and there was a delay in engraftment which may have been confounded by sepsis. The median progression free survival was 26.1 months in MEL200and 27.2 months in MEL140 group. The cumulative incidence of relapse at 3 years was not significantly different between the Mel200 (36.3%) and Mel140 (37.9%) groups. The adjusted HR for relapse was 0.98. Subgroup analysis suggests that in overall survival, progression-free survival, and cumulative incidence of relapse there was no significant advantage associated with melphalan 200 mg/m2.
We formulated to compare a lower dose melphalan to prevent a stormy post-transplant course and prevent patients succumbing to sepsis. This may not be an issue in western countries where gram negative sepsis rates are lower. The biggest worry for us is not to compromise the myeloma outcome due to lower doses of Melphalan in fit patients who achieve complete remission. This study concluded that there is not much of a difference in overall survival, Progression free survival and cumulative incidence of relapse at three years among MEL200 vs MEL140.
Conclusion
We conclude that Melphalan autograft at a dose 140mg/m2 can achieve comparable responses to 200mg/m2 in Indian myeloma patients who are taken to transplant post complete remission. We need a bigger multicentric study and a longer follow up to recommend MEL140 as standard of care in Indian setting.
Keyword(s): Melphalan, Myeloma, Transplant