Contributions
Abstract: PB2187
Type: Publication Only
Background
The CyBorD drug regimen when administered to patients with multiple myeloma results in a complete response rate of 40% in previously untreated multiple myeloma and a complete response rate of 8% in relapsed or refractory myeloma. It has been found that Montelukast and Gemfibrozil when used in poor prognosis multiple myeloma deepens the response and reverses resistance to Bortezomib based treatment (MOM trial). The response was demonstrable within 1 cycle of CyBorD (28 days) and there was no additional toxicity. The question arises as to whether these agents when used up front earlier in the disease process leads to deeper and more rapid response.
Aims
To determine whether montelukast and gemfibrozil when added to bortezomib chemotherapy from the first cycle leads to an increase in complete responses over expected responses and whether the time taken to reach response is faster and deeper.
Methods
Three patients with relapsed/refractory Multiple Myeloma and two patients with high risk de novo disease have been given Montelukast 30mg orally twice daily with Gemfibrozil 600mg orally twice daily in combination with CyBorD regimen. Patient 1 and 2 had progressive disease while on CTD treatment including a patient with multiple soft tissue plasmacytomas and 17p deletion. The third patient had dialysis dependent renal failure for a period of 3 months prior to receiving treatment. The Fourth patient had recurrent nephrotic syndrome on the basis of AL Amyloid previously treated 6 years earlier with CTD. The fifth patient had Multiple Myeloma with suspected cardiac amyloid causing cardiac failure. The expected number of complete responders in this cohort was 1/5 and an expected ORR of 60%.
Results
4/5 patients achieved a complete haematological resonse in paraprotein with a mean time to complete response of less than 35 days. 80% CR.
1/5 patient has achieved a haematological partial response. ORR 100% Expected 2= 40%
chi^2 =14. df =2 p<0.01
Treatment is continuing and it is anticipated that all four patients in complete remission will undergo bone marrow biopsy and minimal residual disease assessment at the completion of four cycles of treatment.
The soft tissue plasmacytomas resolved in 10 days, The symptoms signs of nephrotic syndrome improved markedly in 10 days. The renal failure appears to be improving (lower creatinine , more urine output) in 3 weeks.
One patient was also found to have stage II co-existing breast cancer which partially responded to non breast cancer chemotherapy. There has been a partial response with post mastectomy histology to be reported at the congress.
Patient 1 has been in complete remission for a period of two years.
Conclusion
The addition of Montelukast to standard CyBorD chemotherapy in high risk patients leads to an extremely rapid and much deeper response in most patients treated with CyBorD chemotherapy. There is little toxicity. The ORR is 100% with a haematological CR rate of of 80%. The rate of sCR will be published following further bone marrow studies when all four cycles of CyBorD are completed.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Amyloidosis, bortezomib, Drug sensitivity, Multiple Myeloma
Abstract: PB2187
Type: Publication Only
Background
The CyBorD drug regimen when administered to patients with multiple myeloma results in a complete response rate of 40% in previously untreated multiple myeloma and a complete response rate of 8% in relapsed or refractory myeloma. It has been found that Montelukast and Gemfibrozil when used in poor prognosis multiple myeloma deepens the response and reverses resistance to Bortezomib based treatment (MOM trial). The response was demonstrable within 1 cycle of CyBorD (28 days) and there was no additional toxicity. The question arises as to whether these agents when used up front earlier in the disease process leads to deeper and more rapid response.
Aims
To determine whether montelukast and gemfibrozil when added to bortezomib chemotherapy from the first cycle leads to an increase in complete responses over expected responses and whether the time taken to reach response is faster and deeper.
Methods
Three patients with relapsed/refractory Multiple Myeloma and two patients with high risk de novo disease have been given Montelukast 30mg orally twice daily with Gemfibrozil 600mg orally twice daily in combination with CyBorD regimen. Patient 1 and 2 had progressive disease while on CTD treatment including a patient with multiple soft tissue plasmacytomas and 17p deletion. The third patient had dialysis dependent renal failure for a period of 3 months prior to receiving treatment. The Fourth patient had recurrent nephrotic syndrome on the basis of AL Amyloid previously treated 6 years earlier with CTD. The fifth patient had Multiple Myeloma with suspected cardiac amyloid causing cardiac failure. The expected number of complete responders in this cohort was 1/5 and an expected ORR of 60%.
Results
4/5 patients achieved a complete haematological resonse in paraprotein with a mean time to complete response of less than 35 days. 80% CR.
1/5 patient has achieved a haematological partial response. ORR 100% Expected 2= 40%
chi^2 =14. df =2 p<0.01
Treatment is continuing and it is anticipated that all four patients in complete remission will undergo bone marrow biopsy and minimal residual disease assessment at the completion of four cycles of treatment.
The soft tissue plasmacytomas resolved in 10 days, The symptoms signs of nephrotic syndrome improved markedly in 10 days. The renal failure appears to be improving (lower creatinine , more urine output) in 3 weeks.
One patient was also found to have stage II co-existing breast cancer which partially responded to non breast cancer chemotherapy. There has been a partial response with post mastectomy histology to be reported at the congress.
Patient 1 has been in complete remission for a period of two years.
Conclusion
The addition of Montelukast to standard CyBorD chemotherapy in high risk patients leads to an extremely rapid and much deeper response in most patients treated with CyBorD chemotherapy. There is little toxicity. The ORR is 100% with a haematological CR rate of of 80%. The rate of sCR will be published following further bone marrow studies when all four cycles of CyBorD are completed.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Amyloidosis, bortezomib, Drug sensitivity, Multiple Myeloma