Contributions
Abstract: PB2160
Type: Publication Only
Background
The asthma drug Montelukast has been shown to have many inhibitory physiological effects at an in vitro level that could be used to inhibit malignant processes. There is also no known maximal tolerated dose of this drug. It was thus proposed that that montelukast could be repurposed for use in malignancy. A solitary patient who had rapidly progressive lambda light chain myeloma while on Thalidomide based combination chemotherapy was treated with Montelukast in addition to Bortezomib based chemotherapy. This patient achieved a strict Complete response measured at 12 weeks despite the dire prognosis. A small phase 1 /2 longnitudinal cross over clinical trial was conducted in relapsed and refractory multiple myeloma patients to determine whether this benefit was due to montelukast and to establish whether the treatment is safe.
Aims
To determine whether montelukast combined with bortezomib based therapy is safe.To determine whether montelukast would reverse resistance to chemotherapy in high risk relapsed/refractory/resistant multiple myeloma patients.
Methods
Subjects had previously received a median of five treatments including stem cell transplant. Three of the patients had lambda light chain myeloma. The patients would have been excluded from clinical trials based on refractoriness. Patients were given CyBorD chemotherapy on a 4 week cycle. They received a minimum of two cycles. Paraproteins were measured at the end of each four week cycle. If there had been an increase in the paraprotein from the previous treatment cycle montelukast and gemfibrozil was added to their drug regimen. Five of the six patients had enough measurements and were eligible for review. The paraprotein levels were again measured following each 4 week cycle following montelukast administration. The patients were seen weekly to determine toxicity. The response in paraprotein was compared using a paired t-test as each patient acted as their own control.
Results
The patients had a median of five previous forms of therapy for myeloma including stem cell transplant. The increase in paraprotein on CyBorD was statically significant prior to the addition of montelukast. Three patients received two cycles of montelukast/ CyBorD. Two patients received a solitary cycle. There was no toxicity up to a dose level of montelukast 60mg a day, Gemfibrozil 600mg per day. Addition of these two agents lead to an improvement in the response to combination chemotherapy in all five patients. p<0.01 Student’s T test. Four of the five patients achieved a partial response including a VGPR following the addition of montelukast and gemfibrozil. The other had a partial response in bone marrow alone. The five patients are alive at a median of 15 months post treatment despite having highly advanced and refractory disease. Median progression free survival has not been reached and is over 8 months.
Conclusion
The addition of montelukast and gemfibrozil to standard chemotherapy leads to deeper responses in multiple myeloma patients resistant/refractory to chemotherapy including patients that have progressed following stem cell transplant. The treatment appears extremely effective, is safe and has few to no side effects.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Drug resistance, Drug sensitivity, Multiple Myeloma, Phase I/II
Abstract: PB2160
Type: Publication Only
Background
The asthma drug Montelukast has been shown to have many inhibitory physiological effects at an in vitro level that could be used to inhibit malignant processes. There is also no known maximal tolerated dose of this drug. It was thus proposed that that montelukast could be repurposed for use in malignancy. A solitary patient who had rapidly progressive lambda light chain myeloma while on Thalidomide based combination chemotherapy was treated with Montelukast in addition to Bortezomib based chemotherapy. This patient achieved a strict Complete response measured at 12 weeks despite the dire prognosis. A small phase 1 /2 longnitudinal cross over clinical trial was conducted in relapsed and refractory multiple myeloma patients to determine whether this benefit was due to montelukast and to establish whether the treatment is safe.
Aims
To determine whether montelukast combined with bortezomib based therapy is safe.To determine whether montelukast would reverse resistance to chemotherapy in high risk relapsed/refractory/resistant multiple myeloma patients.
Methods
Subjects had previously received a median of five treatments including stem cell transplant. Three of the patients had lambda light chain myeloma. The patients would have been excluded from clinical trials based on refractoriness. Patients were given CyBorD chemotherapy on a 4 week cycle. They received a minimum of two cycles. Paraproteins were measured at the end of each four week cycle. If there had been an increase in the paraprotein from the previous treatment cycle montelukast and gemfibrozil was added to their drug regimen. Five of the six patients had enough measurements and were eligible for review. The paraprotein levels were again measured following each 4 week cycle following montelukast administration. The patients were seen weekly to determine toxicity. The response in paraprotein was compared using a paired t-test as each patient acted as their own control.
Results
The patients had a median of five previous forms of therapy for myeloma including stem cell transplant. The increase in paraprotein on CyBorD was statically significant prior to the addition of montelukast. Three patients received two cycles of montelukast/ CyBorD. Two patients received a solitary cycle. There was no toxicity up to a dose level of montelukast 60mg a day, Gemfibrozil 600mg per day. Addition of these two agents lead to an improvement in the response to combination chemotherapy in all five patients. p<0.01 Student’s T test. Four of the five patients achieved a partial response including a VGPR following the addition of montelukast and gemfibrozil. The other had a partial response in bone marrow alone. The five patients are alive at a median of 15 months post treatment despite having highly advanced and refractory disease. Median progression free survival has not been reached and is over 8 months.
Conclusion
The addition of montelukast and gemfibrozil to standard chemotherapy leads to deeper responses in multiple myeloma patients resistant/refractory to chemotherapy including patients that have progressed following stem cell transplant. The treatment appears extremely effective, is safe and has few to no side effects.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Drug resistance, Drug sensitivity, Multiple Myeloma, Phase I/II