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CHICAGO—Cord blood (CB) is a viable source of natural killer (NK) cells for adoptive cellular therapy for multiple myeloma (MM), according to a speaker at the 2018 ASCO Annual Meeting.
Ex-vivo expanded cord blood NK cells were well tolerated without significant graft-versus-host disease (GVHD) or cytokine release syndrome (CRS) in a phase 2 study.
Nina Shah, MD, of the University of California San Francisco, reported these results as abstract 8006.*
The phase 2 study (NCT01729091) included 33 patients with symptomatic MM who were appropriate candidates for autologous stem cell transplant (ASCT).
For each patient, investigators chose cord blood units with at least a 4/6 match at HLA-A, -B and –DR.
Prior to the autologous graft, patients received lenalidomide and melphalan. Lenalidomide was given based on preclinical data suggesting synergy between that immunomodulatory agent and NK cells, Dr Shah said.
Patients were a median age of 59 (range, 25 – 72), 36% had a history of progressive disease or relapse, and 73% had adverse cytogenetics/FISH, were ISS III, or had a history of progressive disease or relapse.
Results
Dr Shah observed that in a generally high-risk population, responses to treatment with cord blood NK cells in the setting of ASCT were “encouraging,” with 79% of patients achieving very good partial response (VGPR) or better.
Twenty-one patients (64%) achieved a complete response (CR) or near CR. And 61% achieved minimal residual disease (MRD) negativity by day 100.
Patients had an estimated 3-year progression-free survival of 52%.
Three patients died, all from disease progression, and 13 patients have progressed.
The investigators observed no infusional toxicities, no GVHD, no CRS, and no neurotoxicity.
One patient experienced graft failure and was rescued with an autologous back-up graft.
"We are able to detect the donor-derived NK cells up to 13 days after infusion,” Dr Shah said, “but I think a more sensitive analysis with flow chimerism will not only allow us to detect more patients, but also better interrogate them to truly understand the in vivo phenotype and activation status of these cells."
Dr Shah indicated she and her colleagues became interested in studying cord blood for NK cell therapy because it is a known source of hematopoietic cells that is immediately available, does not require donor manipulation, and has more flexibility in genetic matching.
Previously, Dr Shah and colleagues conducted a phase 1 study, in which 12 patients received cord blood NK cells up to a dose of 1 x 108 NK cells/kg. “This was determined to be adequate and safe to move on to the phase 2,” she said.
Despite encouraging results, more research needs to be done, according to Dr Shah. “I don't think this is the end-all, be-all for NK cell therapy.”
Some future directions include combination with antibody therapy, improving NK persistence in vivo using cytokine manipulation, and possibly engineering chimeric antigen receptor (CAR)-modified NK cells, Dr Shah observed.
It’s also possible that HLA match may not be needed: “If that is the case, we will truly have an off-the-shelf source of NK cells that we can apply more readily to various patients,” she said.
The study was supported by Celgene Corporation, Stading-Younger Cancer Research Foundation, and the MD Anderson High-Risk Multiple Myeloma Moonshot Project.
*Data in the presentation differ from the abstract.
CHICAGO—Cord blood (CB) is a viable source of natural killer (NK) cells for adoptive cellular therapy for multiple myeloma (MM), according to a speaker at the 2018 ASCO Annual Meeting.
Ex-vivo expanded cord blood NK cells were well tolerated without significant graft-versus-host disease (GVHD) or cytokine release syndrome (CRS) in a phase 2 study.
Nina Shah, MD, of the University of California San Francisco, reported these results as abstract 8006.*
The phase 2 study (NCT01729091) included 33 patients with symptomatic MM who were appropriate candidates for autologous stem cell transplant (ASCT).
For each patient, investigators chose cord blood units with at least a 4/6 match at HLA-A, -B and –DR.
Prior to the autologous graft, patients received lenalidomide and melphalan. Lenalidomide was given based on preclinical data suggesting synergy between that immunomodulatory agent and NK cells, Dr Shah said.
Patients were a median age of 59 (range, 25 – 72), 36% had a history of progressive disease or relapse, and 73% had adverse cytogenetics/FISH, were ISS III, or had a history of progressive disease or relapse.
Results
Dr Shah observed that in a generally high-risk population, responses to treatment with cord blood NK cells in the setting of ASCT were “encouraging,” with 79% of patients achieving very good partial response (VGPR) or better.
Twenty-one patients (64%) achieved a complete response (CR) or near CR. And 61% achieved minimal residual disease (MRD) negativity by day 100.
Patients had an estimated 3-year progression-free survival of 52%.
Three patients died, all from disease progression, and 13 patients have progressed.
The investigators observed no infusional toxicities, no GVHD, no CRS, and no neurotoxicity.
One patient experienced graft failure and was rescued with an autologous back-up graft.
"We are able to detect the donor-derived NK cells up to 13 days after infusion,” Dr Shah said, “but I think a more sensitive analysis with flow chimerism will not only allow us to detect more patients, but also better interrogate them to truly understand the in vivo phenotype and activation status of these cells."
Dr Shah indicated she and her colleagues became interested in studying cord blood for NK cell therapy because it is a known source of hematopoietic cells that is immediately available, does not require donor manipulation, and has more flexibility in genetic matching.
Previously, Dr Shah and colleagues conducted a phase 1 study, in which 12 patients received cord blood NK cells up to a dose of 1 x 108 NK cells/kg. “This was determined to be adequate and safe to move on to the phase 2,” she said.
Despite encouraging results, more research needs to be done, according to Dr Shah. “I don't think this is the end-all, be-all for NK cell therapy.”
Some future directions include combination with antibody therapy, improving NK persistence in vivo using cytokine manipulation, and possibly engineering chimeric antigen receptor (CAR)-modified NK cells, Dr Shah observed.
It’s also possible that HLA match may not be needed: “If that is the case, we will truly have an off-the-shelf source of NK cells that we can apply more readily to various patients,” she said.
The study was supported by Celgene Corporation, Stading-Younger Cancer Research Foundation, and the MD Anderson High-Risk Multiple Myeloma Moonshot Project.
*Data in the presentation differ from the abstract.
CHICAGO—Cord blood (CB) is a viable source of natural killer (NK) cells for adoptive cellular therapy for multiple myeloma (MM), according to a speaker at the 2018 ASCO Annual Meeting.
Ex-vivo expanded cord blood NK cells were well tolerated without significant graft-versus-host disease (GVHD) or cytokine release syndrome (CRS) in a phase 2 study.
Nina Shah, MD, of the University of California San Francisco, reported these results as abstract 8006.*
The phase 2 study (NCT01729091) included 33 patients with symptomatic MM who were appropriate candidates for autologous stem cell transplant (ASCT).
For each patient, investigators chose cord blood units with at least a 4/6 match at HLA-A, -B and –DR.
Prior to the autologous graft, patients received lenalidomide and melphalan. Lenalidomide was given based on preclinical data suggesting synergy between that immunomodulatory agent and NK cells, Dr Shah said.
Patients were a median age of 59 (range, 25 – 72), 36% had a history of progressive disease or relapse, and 73% had adverse cytogenetics/FISH, were ISS III, or had a history of progressive disease or relapse.
Results
Dr Shah observed that in a generally high-risk population, responses to treatment with cord blood NK cells in the setting of ASCT were “encouraging,” with 79% of patients achieving very good partial response (VGPR) or better.
Twenty-one patients (64%) achieved a complete response (CR) or near CR. And 61% achieved minimal residual disease (MRD) negativity by day 100.
Patients had an estimated 3-year progression-free survival of 52%.
Three patients died, all from disease progression, and 13 patients have progressed.
The investigators observed no infusional toxicities, no GVHD, no CRS, and no neurotoxicity.
One patient experienced graft failure and was rescued with an autologous back-up graft.
"We are able to detect the donor-derived NK cells up to 13 days after infusion,” Dr Shah said, “but I think a more sensitive analysis with flow chimerism will not only allow us to detect more patients, but also better interrogate them to truly understand the in vivo phenotype and activation status of these cells."
Dr Shah indicated she and her colleagues became interested in studying cord blood for NK cell therapy because it is a known source of hematopoietic cells that is immediately available, does not require donor manipulation, and has more flexibility in genetic matching.
Previously, Dr Shah and colleagues conducted a phase 1 study, in which 12 patients received cord blood NK cells up to a dose of 1 x 108 NK cells/kg. “This was determined to be adequate and safe to move on to the phase 2,” she said.
Despite encouraging results, more research needs to be done, according to Dr Shah. “I don't think this is the end-all, be-all for NK cell therapy.”
Some future directions include combination with antibody therapy, improving NK persistence in vivo using cytokine manipulation, and possibly engineering chimeric antigen receptor (CAR)-modified NK cells, Dr Shah observed.
It’s also possible that HLA match may not be needed: “If that is the case, we will truly have an off-the-shelf source of NK cells that we can apply more readily to various patients,” she said.
The study was supported by Celgene Corporation, Stading-Younger Cancer Research Foundation, and the MD Anderson High-Risk Multiple Myeloma Moonshot Project.
*Data in the presentation differ from the abstract.