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SAN FRANCISCO—The oral proteasome inhibitor ixazomib induces high-quality hematologic responses in patients with relapsed/refractory systemic light-chain (AL) amyloidosis, with generally manageable side effects, a phase 1 study suggests.
Preliminary results from this study indicated that ixazomib had promise for treating AL amyloidosis.
Now, researchers have reported updated safety data and figures for hematologic and organ responses, progression-free survival, and overall survival.
The study was presented at the 2014 ASH Annual Meeting (abstract 3450) 5 days after the US Food and Drug Administration granted ixazomib breakthrough status for the treatment of relapsed/refractory AL amyloidosis.
“To have an oral drug that is well-tolerated and extremely effective in patients exposed to all lines of other therapy is remarkable in this disease,” said study investigator Giampaolo Merlini, MD, of the Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, at the University of Pavia in Italy.
He and his colleagues evaluated ixazomib in 22 patients with a median age of 65 years. They were heavily pretreated, with 95% exposed to melphalan and 73% to bortezomib.
The patients received 4 mg of ixazomib on days 1, 8, and 15 of 28-day cycles for up to 12 cycles. Those who did not achieve a hematologic partial response after 3 cycles received added dexamethasone.
In 21 evaluable patients, the overall response rate was 52%, including a complete response and very good partial response in 43% of patients.
Dr Merlini noted that responses were deep and durable. And the high response rates translated into high organ response rates.
“End-organ damage is what kills patients,” he said. “In 18 evaluable patients, both the heart and kidney response rate was 45%.”
At 1 year, progression-free survival was 60%. At 2 years, overall survival was 63%.
The drug was well-tolerated as well. The 3 most common side effects—nausea, diarrhea, and fatigue—were mild and seen in about 30% of patients.
Severe grade 3 or higher side effects included thrombocytopenia, diarrhea, and rash, occurring in about 10% of patients.
The development program for ixazomib in AL amyloidosis progressed directly from this phase 1 trial to a phase 3 study, TOURMALINE-AL1. The trial is already underway, with 80 patients enrolled thus far.
TOURMALINE-AL1 investigators are comparing ixazomib plus dexamethasone to physician’s choice of treatment in patients with relapsed/refractory AL amyloidosis. Data from this trial are expected by the end of 2015.
“For the first time, we have evidence of an oral drug that is extremely effective,” Dr Merlini said. “We need to see the phase 3 data, but it could be a breakthrough.” 
Photo courtesy of ASH
SAN FRANCISCO—The oral proteasome inhibitor ixazomib induces high-quality hematologic responses in patients with relapsed/refractory systemic light-chain (AL) amyloidosis, with generally manageable side effects, a phase 1 study suggests.
Preliminary results from this study indicated that ixazomib had promise for treating AL amyloidosis.
Now, researchers have reported updated safety data and figures for hematologic and organ responses, progression-free survival, and overall survival.
The study was presented at the 2014 ASH Annual Meeting (abstract 3450) 5 days after the US Food and Drug Administration granted ixazomib breakthrough status for the treatment of relapsed/refractory AL amyloidosis.
“To have an oral drug that is well-tolerated and extremely effective in patients exposed to all lines of other therapy is remarkable in this disease,” said study investigator Giampaolo Merlini, MD, of the Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, at the University of Pavia in Italy.
He and his colleagues evaluated ixazomib in 22 patients with a median age of 65 years. They were heavily pretreated, with 95% exposed to melphalan and 73% to bortezomib.
The patients received 4 mg of ixazomib on days 1, 8, and 15 of 28-day cycles for up to 12 cycles. Those who did not achieve a hematologic partial response after 3 cycles received added dexamethasone.
In 21 evaluable patients, the overall response rate was 52%, including a complete response and very good partial response in 43% of patients.
Dr Merlini noted that responses were deep and durable. And the high response rates translated into high organ response rates.
“End-organ damage is what kills patients,” he said. “In 18 evaluable patients, both the heart and kidney response rate was 45%.”
At 1 year, progression-free survival was 60%. At 2 years, overall survival was 63%.
The drug was well-tolerated as well. The 3 most common side effects—nausea, diarrhea, and fatigue—were mild and seen in about 30% of patients.
Severe grade 3 or higher side effects included thrombocytopenia, diarrhea, and rash, occurring in about 10% of patients.
The development program for ixazomib in AL amyloidosis progressed directly from this phase 1 trial to a phase 3 study, TOURMALINE-AL1. The trial is already underway, with 80 patients enrolled thus far.
TOURMALINE-AL1 investigators are comparing ixazomib plus dexamethasone to physician’s choice of treatment in patients with relapsed/refractory AL amyloidosis. Data from this trial are expected by the end of 2015.
“For the first time, we have evidence of an oral drug that is extremely effective,” Dr Merlini said. “We need to see the phase 3 data, but it could be a breakthrough.”
Photo courtesy of ASH
SAN FRANCISCO—The oral proteasome inhibitor ixazomib induces high-quality hematologic responses in patients with relapsed/refractory systemic light-chain (AL) amyloidosis, with generally manageable side effects, a phase 1 study suggests.
Preliminary results from this study indicated that ixazomib had promise for treating AL amyloidosis.
Now, researchers have reported updated safety data and figures for hematologic and organ responses, progression-free survival, and overall survival.
The study was presented at the 2014 ASH Annual Meeting (abstract 3450) 5 days after the US Food and Drug Administration granted ixazomib breakthrough status for the treatment of relapsed/refractory AL amyloidosis.
“To have an oral drug that is well-tolerated and extremely effective in patients exposed to all lines of other therapy is remarkable in this disease,” said study investigator Giampaolo Merlini, MD, of the Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, at the University of Pavia in Italy.
He and his colleagues evaluated ixazomib in 22 patients with a median age of 65 years. They were heavily pretreated, with 95% exposed to melphalan and 73% to bortezomib.
The patients received 4 mg of ixazomib on days 1, 8, and 15 of 28-day cycles for up to 12 cycles. Those who did not achieve a hematologic partial response after 3 cycles received added dexamethasone.
In 21 evaluable patients, the overall response rate was 52%, including a complete response and very good partial response in 43% of patients.
Dr Merlini noted that responses were deep and durable. And the high response rates translated into high organ response rates.
“End-organ damage is what kills patients,” he said. “In 18 evaluable patients, both the heart and kidney response rate was 45%.”
At 1 year, progression-free survival was 60%. At 2 years, overall survival was 63%.
The drug was well-tolerated as well. The 3 most common side effects—nausea, diarrhea, and fatigue—were mild and seen in about 30% of patients.
Severe grade 3 or higher side effects included thrombocytopenia, diarrhea, and rash, occurring in about 10% of patients.
The development program for ixazomib in AL amyloidosis progressed directly from this phase 1 trial to a phase 3 study, TOURMALINE-AL1. The trial is already underway, with 80 patients enrolled thus far.
TOURMALINE-AL1 investigators are comparing ixazomib plus dexamethasone to physician’s choice of treatment in patients with relapsed/refractory AL amyloidosis. Data from this trial are expected by the end of 2015.
“For the first time, we have evidence of an oral drug that is extremely effective,” Dr Merlini said. “We need to see the phase 3 data, but it could be a breakthrough.”