CHICAGO -- Medical science may on the verge of finding antibody-based treatments for multiple myeloma, although they are likely to be used in combination with other types of therapy, a researcher said here.
"We appear to be heading toward finding more than one 'rituximab' [Rituxan] for multiple myeloma," said Nikhil Munshi, MD, of Harvard Medical School in Boston, referring to the highly successful antibody therapy against diseases involving B cells.
At least 10 such antibodies are in clinical development, said Munshi, who was an invited discussant in an American Society of Clinical Oncology session dedicated to multiple myeloma.
But in general, he said, the agents in development have a modest anti-cancer effect when given alone, and so they are being developed for use in combination with other drugs.
Among the most promising, Munshi said, is elotuzumab, a humanized monoclonal antibody that targets a cell surface glycoprotein highly expressed on multiple myeloma cells.
It's given in combination with oral lenalidomide (Revlimid) and low-dose dexamethasone, according to Philippe Moreau, MD, of the University Hospital Nantes in Nantes, France.
And in a phase I/II study, the combination yielded an objective response rate of 82% among 98 patients with relapsed or refractory disease, according to Moreau.
Among the 98 patients, he reported, 9% had a complete response, 33% had a very good partial response, and 40% had a partial response. Another 14% had stable disease, he said.
After a median follow-up of 9.4 months, the median progression-free survival had not yet been reached, he said.
The response rate was "very high" for a clinical trial in multiple myeloma, Moreau said, especially considering that patients in the trial had been on as many as three previous treatment regimens.
The antibody was given by infusion and early on, patients had difficult infusion reactions, including nausea and headache. These reactions were dealt with later in the trial with premedication regimens, Moreau said.
The combination was "generally well tolerated," he said, with most of the occurrence of toxicities -- neutropenia, thrombocytopenia, and lymphopenia -- that are generally associated with lenalidomide.
A phase III trial of the combination is under way.
The session also offered an early look at two other antibody-based therapies.
Lorvotuzumab mertansine is an antibody-drug conjugate that is being developed to treat patients with relapsed or refractory disease, whose multiple myeloma cells express the molecule CD56, according to Jesus Berdeja, MD, of the Sarah Cannon Research Institute in Nashville, Tenn.
The antibody targets the CD56-positive cells, Berdeja said, and delivers an attached cytotoxic agent, DM1, derived from maytansine, for the knockout punch.
Like elotuzumab, the drug is given with lenalidomide and dexamethasone, Berdeja reported.
In a phase I study, aimed at finding the best of three doses, 13 patients had an evaluable response, Berdeja, and eight had either a very good partial response or a partial response.
The most common adverse event was peripheral neuropathy (in the two higher doses) that required dose reduction, he reported, although several patients continued to have a response after their dose was cut.
The researchers will continue testing the combination with the lorvotuzumab mertansine given at a dose of 75 mg/meter2, a level at which he said dose reductions were not required.
Finally, researchers reported phase I data on LY2127399, a human monoclonal antibody that neutralizes the B-cell activating factor or BAFF.
Like the other antibodies, it was also given in combination with another drug, bortezomib (Velcade), which is used to treat patients with relapsed disease, according to Noopur Raje, MD, of Massachusetts General Hospital in Boston.
The main goal of the study was to settle on a dose for future testing. Although there was little difference in response according to dose, the researchers decided on 100 mg, she said.
Among the 20 patients with relapsed or refractory disease, she reported, there were two complete responses, three very good partial responses, and six partial responses.
The median duration of response was 9.7 months, she said.
There was one death and six adverse events, but only one case of pancreatitis was potentially related to the study drug, Raje reported.
The patient who died had dropped out of the study beforehand because of disease progression, she said.
"We appear to be heading toward finding more than one 'rituximab' [Rituxan] for multiple myeloma," said Nikhil Munshi, MD, of Harvard Medical School in Boston, referring to the highly successful antibody therapy against diseases involving B cells.
At least 10 such antibodies are in clinical development, said Munshi, who was an invited discussant in an American Society of Clinical Oncology session dedicated to multiple myeloma.
But in general, he said, the agents in development have a modest anti-cancer effect when given alone, and so they are being developed for use in combination with other drugs.
Among the most promising, Munshi said, is elotuzumab, a humanized monoclonal antibody that targets a cell surface glycoprotein highly expressed on multiple myeloma cells.
It's given in combination with oral lenalidomide (Revlimid) and low-dose dexamethasone, according to Philippe Moreau, MD, of the University Hospital Nantes in Nantes, France.
And in a phase I/II study, the combination yielded an objective response rate of 82% among 98 patients with relapsed or refractory disease, according to Moreau.
Among the 98 patients, he reported, 9% had a complete response, 33% had a very good partial response, and 40% had a partial response. Another 14% had stable disease, he said.
After a median follow-up of 9.4 months, the median progression-free survival had not yet been reached, he said.
The response rate was "very high" for a clinical trial in multiple myeloma, Moreau said, especially considering that patients in the trial had been on as many as three previous treatment regimens.
The antibody was given by infusion and early on, patients had difficult infusion reactions, including nausea and headache. These reactions were dealt with later in the trial with premedication regimens, Moreau said.
The combination was "generally well tolerated," he said, with most of the occurrence of toxicities -- neutropenia, thrombocytopenia, and lymphopenia -- that are generally associated with lenalidomide.
A phase III trial of the combination is under way.
The session also offered an early look at two other antibody-based therapies.
Lorvotuzumab mertansine is an antibody-drug conjugate that is being developed to treat patients with relapsed or refractory disease, whose multiple myeloma cells express the molecule CD56, according to Jesus Berdeja, MD, of the Sarah Cannon Research Institute in Nashville, Tenn.
The antibody targets the CD56-positive cells, Berdeja said, and delivers an attached cytotoxic agent, DM1, derived from maytansine, for the knockout punch.
Like elotuzumab, the drug is given with lenalidomide and dexamethasone, Berdeja reported.
In a phase I study, aimed at finding the best of three doses, 13 patients had an evaluable response, Berdeja, and eight had either a very good partial response or a partial response.
The most common adverse event was peripheral neuropathy (in the two higher doses) that required dose reduction, he reported, although several patients continued to have a response after their dose was cut.
The researchers will continue testing the combination with the lorvotuzumab mertansine given at a dose of 75 mg/meter2, a level at which he said dose reductions were not required.
Finally, researchers reported phase I data on LY2127399, a human monoclonal antibody that neutralizes the B-cell activating factor or BAFF.
Like the other antibodies, it was also given in combination with another drug, bortezomib (Velcade), which is used to treat patients with relapsed disease, according to Noopur Raje, MD, of Massachusetts General Hospital in Boston.
The main goal of the study was to settle on a dose for future testing. Although there was little difference in response according to dose, the researchers decided on 100 mg, she said.
Among the 20 patients with relapsed or refractory disease, she reported, there were two complete responses, three very good partial responses, and six partial responses.
The median duration of response was 9.7 months, she said.
There was one death and six adverse events, but only one case of pancreatitis was potentially related to the study drug, Raje reported.
The patient who died had dropped out of the study beforehand because of disease progression, she said.
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