20 min
AUDIO JOURNAL OF ONCOLOGY—Fast Durable Responses to Bi-Specific Antibody Therapy In Heavily Pre-Treated Multiple Myeloma Audio Journal of Oncology Podcast
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- Science
January 10, 2023
Fast Durable Responses to Bi-Specific Antibody Therapy In Heavily Pre-Treated Multiple Myeloma
INTERVIEW WITH:
Ajai Chari MD, Associate Professor of Medicine and Director of Clinical Research in the Multiple Myeloma Program at Mount Sinai School of Medicine in New York, USA.
NEW ORLEANS, USA—The bispecific antibody talquetamab, classed as a “T-cell redirecting therapy” achieved high response rates in the phase one/two multi-national MonumenTAL-1 study investigating 288 patients who had heavily pre-treated refractory multiple myeloma.
Findings reported at the American Society of Hematology 2022 Annual Meeting showed that nearly three-quarters of patients treated had “complete” or “very good partial” responses within one or two months, and median response durations of around nine months.https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.8015
“Remarkably in this unmet need we saw response rates of 73 to 74 per cent. The responses were maintained in triple-class refractory patients, penta-drug refractory patients, ISS (International Staging System) three high-risk disease,” said Ajai Chari MD, Associate Professor of Medicine and Director of Clinical Research in the Multiple Myeloma Program at Mount Sinai School of Medicine in New York, USA.
“The median time to response was one month—which is outstanding. And the median time to “best response” was slightly over two months—which is great, because it means that these patients who had explosive disease (these are not CAR-T cherry-picked patients with really indolent progression) were benefiting in high percentages—and quickly, and deeply,” Chari told the Audio Journal of Oncology.
Although patients with extra-medullary disease had fared slightly less well, their responses had still been good, he said. “Even there, there was an impressive 50 per cent response rate.”
Talquetamab was an off-the-shelf bispecific antibody, that binds to both T cells and multiple myeloma cells, said Chari. This facilitates an immune response to destroy myeloma cells by bringing T cells to the cancer. Its twin targets were the CD3 T-cell receptors and the cancer cell surface receptor known as G protein-coupled receptor family C group 5 member D (GPRC5D).
“[Previously] we only had naked antibodies. And a bispecific antibody is different. Like with all antibodies it has the Y-shaped structure, but unlike typical antibodies it binds two different targets. Â One target is the T cell—with CD3; and the other target is GPRC5D, which is a novel target in myeloma. It’s over-expressed particularly on malignant plasma cells, less so on normal plasma cells, and—importantly—not on the hematopoietic stem cell compartment—Which we think is a favorable finding,” said Chari.
“You basically can engage the patient’s own T-cells to try to attack the myeloma. And it’s a little surprising how remarkable this whole approach has been: Because patients with myeloma who are entering these studies have typically five to six lines of therapy over six years, are usually in their late sixties [or] early seventies, and you wouldn’t think that their T-cells would even be robust, and fit, and present, enough to generate results—let alone the outstanding results we’re seeing,” he said.
In the MonumenTAL-1 study, patients with relapsed/refractory multiple myeloma, were treated with either of two recommended dosing regimens: 0.40 mg/kg of talquetamab subcutaneously at weekly intervals, or 0.80 mg/kg every other week.
Results
Patients in the weekly and bi-weekly dose regimens (equivalent in overall dose intensity) had similar outcomes in terms of response rates and toxicities. Nearly a third of patients had complete responses. More than half had “very good” partial responses. The responses deepened with time, and conti
January 10, 2023
Fast Durable Responses to Bi-Specific Antibody Therapy In Heavily Pre-Treated Multiple Myeloma
INTERVIEW WITH:
Ajai Chari MD, Associate Professor of Medicine and Director of Clinical Research in the Multiple Myeloma Program at Mount Sinai School of Medicine in New York, USA.
NEW ORLEANS, USA—The bispecific antibody talquetamab, classed as a “T-cell redirecting therapy” achieved high response rates in the phase one/two multi-national MonumenTAL-1 study investigating 288 patients who had heavily pre-treated refractory multiple myeloma.
Findings reported at the American Society of Hematology 2022 Annual Meeting showed that nearly three-quarters of patients treated had “complete” or “very good partial” responses within one or two months, and median response durations of around nine months.https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.8015
“Remarkably in this unmet need we saw response rates of 73 to 74 per cent. The responses were maintained in triple-class refractory patients, penta-drug refractory patients, ISS (International Staging System) three high-risk disease,” said Ajai Chari MD, Associate Professor of Medicine and Director of Clinical Research in the Multiple Myeloma Program at Mount Sinai School of Medicine in New York, USA.
“The median time to response was one month—which is outstanding. And the median time to “best response” was slightly over two months—which is great, because it means that these patients who had explosive disease (these are not CAR-T cherry-picked patients with really indolent progression) were benefiting in high percentages—and quickly, and deeply,” Chari told the Audio Journal of Oncology.
Although patients with extra-medullary disease had fared slightly less well, their responses had still been good, he said. “Even there, there was an impressive 50 per cent response rate.”
Talquetamab was an off-the-shelf bispecific antibody, that binds to both T cells and multiple myeloma cells, said Chari. This facilitates an immune response to destroy myeloma cells by bringing T cells to the cancer. Its twin targets were the CD3 T-cell receptors and the cancer cell surface receptor known as G protein-coupled receptor family C group 5 member D (GPRC5D).
“[Previously] we only had naked antibodies. And a bispecific antibody is different. Like with all antibodies it has the Y-shaped structure, but unlike typical antibodies it binds two different targets. Â One target is the T cell—with CD3; and the other target is GPRC5D, which is a novel target in myeloma. It’s over-expressed particularly on malignant plasma cells, less so on normal plasma cells, and—importantly—not on the hematopoietic stem cell compartment—Which we think is a favorable finding,” said Chari.
“You basically can engage the patient’s own T-cells to try to attack the myeloma. And it’s a little surprising how remarkable this whole approach has been: Because patients with myeloma who are entering these studies have typically five to six lines of therapy over six years, are usually in their late sixties [or] early seventies, and you wouldn’t think that their T-cells would even be robust, and fit, and present, enough to generate results—let alone the outstanding results we’re seeing,” he said.
In the MonumenTAL-1 study, patients with relapsed/refractory multiple myeloma, were treated with either of two recommended dosing regimens: 0.40 mg/kg of talquetamab subcutaneously at weekly intervals, or 0.80 mg/kg every other week.
Results
Patients in the weekly and bi-weekly dose regimens (equivalent in overall dose intensity) had similar outcomes in terms of response rates and toxicities. Nearly a third of patients had complete responses. More than half had “very good” partial responses. The responses deepened with time, and conti
20 min