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in the bone marrow
HONOLULU—Early results from a pilot study suggest an investigational agent can effectively mobilize hematopoietic stem cells (HSCs) in healthy transplant donors.
The agent, CDX-301 (recombinant human Flt3 ligand), is a hematopoietic cytokine designed to expand dendritic cells and HSCs.
For the study, researchers tested CDX-301 in sibling-matched donors for hematopoietic stem cell transplant (HSCT) recipients with hematologic malignancies.
The team reported early results with 4 donor/recipient pairs at the 2016 BMT Tandem Meetings (abstract 479). The research was sponsored by Celldex Therapeutics, Inc., the company developing CDX-301.
Donor results
The donors received CDX-301 at 75 μg/kg/day for 5 days. Leukapheresis began on day 6 if the peripheral blood CD34+ count was 7/μL or greater. The goal CD34+ yield was at least 2x106 per kilogram of recipient weight collected in 2 days of leukapheresis or less.
The donors could receive rescue plerixafor if the peripheral blood CD34+ count was less than 7/μL by day 8 or if the total CD34+ yield was less than 1x106/kg after the second day of leukapheresis.
The researchers analyzed CDX-301-mobilized cells by flow cytometry and compared them to historical data for peripheral blood grafts mobilized by granulocyte colony-stimulating factor (G-CSF).
Compared to the G-CSF-mobilized grafts, CDX-301-mobilized grafts had an increase in CD127+ (IL-7R) naïve T cells, γδ T cells, natural killer cells, and B cells.
The CDX-301-mobilized grafts were more enriched with plasmacytoid dendritic cells. And dendritic cells from the CDX-301 grafts had a more mature phenotype, expressing CD80 and CD86.
“From these data and preclinical studies, CDX-301 appears to be an effective, targeted approach to mobilization comparable to G-CSF,” said Steven Devine, MD, of The Ohio State Comprehensive Cancer Center in Columbus.
“With a relatively short course of treatment, we are observing specificity for mobilized stem cells and a lack of toxicity, instead of broad cellular mobilization and side effects.”
CDX-301 related adverse events included dizziness (grade 2), back pain (grade 1), arthralgia (grade 1), injection site reaction (2 grade 1), dyspepsia (1 grade 1, 1 grade 2), and decreased platelet count (2 grade 1). There were no grade 3/4 adverse events.
Recipient results
Thus far, 4 recipients have undergone HSCT with CDX-301-mobilized grafts. Recipient 1 had acute myeloid leukemia, recipients 2 and 3 had mantle cell lymphoma, and recipient 4 had chronic myeloid leukemia.
Recipients 1 through 3 received myeloablative conditioning, while recipient 4 received reduced-intensity conditioning. All patients received standard graft-vs-host disease (GVHD) prophylaxis (tacrolimus and methotrexate).
Recipient 4 has not yet engrafted. The other 3 had both neutrophil engraftment (day 17, 18, and 19) and platelet engraftment (day 14, 25, and 40).
There have been no infectious complications, and recipients 1 and 3 have not developed GVHD.
Recipient 2 developed steroid-responsive, grade 2, upper gastrointestinal GVHD on day 18, followed by grade 1 skin GVHD on day 50 that progressed to stage 3. Overall, the patient had grade 2 GVHD on day 64. The patient’s lymphoma has also progressed.
The researchers said these results suggest CDX-301 is well tolerated and can mobilize CD34+ cells when given as a single agent. They said recipients experienced successful engraftment in an expected time frame.
And the additional naïve T cells and plasmacytoid dendritic cells in CDX-301-mobilized grafts (compared to G-CSF-mobilized grafts) may provide better outcomes in HSCT recipients.
Now, the researchers plan to explore CDX-301 in combination with plerixafor. Additional donor/patient pairs are being accrued to a second study cohort. 
in the bone marrow
HONOLULU—Early results from a pilot study suggest an investigational agent can effectively mobilize hematopoietic stem cells (HSCs) in healthy transplant donors.
The agent, CDX-301 (recombinant human Flt3 ligand), is a hematopoietic cytokine designed to expand dendritic cells and HSCs.
For the study, researchers tested CDX-301 in sibling-matched donors for hematopoietic stem cell transplant (HSCT) recipients with hematologic malignancies.
The team reported early results with 4 donor/recipient pairs at the 2016 BMT Tandem Meetings (abstract 479). The research was sponsored by Celldex Therapeutics, Inc., the company developing CDX-301.
Donor results
The donors received CDX-301 at 75 μg/kg/day for 5 days. Leukapheresis began on day 6 if the peripheral blood CD34+ count was 7/μL or greater. The goal CD34+ yield was at least 2x106 per kilogram of recipient weight collected in 2 days of leukapheresis or less.
The donors could receive rescue plerixafor if the peripheral blood CD34+ count was less than 7/μL by day 8 or if the total CD34+ yield was less than 1x106/kg after the second day of leukapheresis.
The researchers analyzed CDX-301-mobilized cells by flow cytometry and compared them to historical data for peripheral blood grafts mobilized by granulocyte colony-stimulating factor (G-CSF).
Compared to the G-CSF-mobilized grafts, CDX-301-mobilized grafts had an increase in CD127+ (IL-7R) naïve T cells, γδ T cells, natural killer cells, and B cells.
The CDX-301-mobilized grafts were more enriched with plasmacytoid dendritic cells. And dendritic cells from the CDX-301 grafts had a more mature phenotype, expressing CD80 and CD86.
“From these data and preclinical studies, CDX-301 appears to be an effective, targeted approach to mobilization comparable to G-CSF,” said Steven Devine, MD, of The Ohio State Comprehensive Cancer Center in Columbus.
“With a relatively short course of treatment, we are observing specificity for mobilized stem cells and a lack of toxicity, instead of broad cellular mobilization and side effects.”
CDX-301 related adverse events included dizziness (grade 2), back pain (grade 1), arthralgia (grade 1), injection site reaction (2 grade 1), dyspepsia (1 grade 1, 1 grade 2), and decreased platelet count (2 grade 1). There were no grade 3/4 adverse events.
Recipient results
Thus far, 4 recipients have undergone HSCT with CDX-301-mobilized grafts. Recipient 1 had acute myeloid leukemia, recipients 2 and 3 had mantle cell lymphoma, and recipient 4 had chronic myeloid leukemia.
Recipients 1 through 3 received myeloablative conditioning, while recipient 4 received reduced-intensity conditioning. All patients received standard graft-vs-host disease (GVHD) prophylaxis (tacrolimus and methotrexate).
Recipient 4 has not yet engrafted. The other 3 had both neutrophil engraftment (day 17, 18, and 19) and platelet engraftment (day 14, 25, and 40).
There have been no infectious complications, and recipients 1 and 3 have not developed GVHD.
Recipient 2 developed steroid-responsive, grade 2, upper gastrointestinal GVHD on day 18, followed by grade 1 skin GVHD on day 50 that progressed to stage 3. Overall, the patient had grade 2 GVHD on day 64. The patient’s lymphoma has also progressed.
The researchers said these results suggest CDX-301 is well tolerated and can mobilize CD34+ cells when given as a single agent. They said recipients experienced successful engraftment in an expected time frame.
And the additional naïve T cells and plasmacytoid dendritic cells in CDX-301-mobilized grafts (compared to G-CSF-mobilized grafts) may provide better outcomes in HSCT recipients.
Now, the researchers plan to explore CDX-301 in combination with plerixafor. Additional donor/patient pairs are being accrued to a second study cohort.
in the bone marrow
HONOLULU—Early results from a pilot study suggest an investigational agent can effectively mobilize hematopoietic stem cells (HSCs) in healthy transplant donors.
The agent, CDX-301 (recombinant human Flt3 ligand), is a hematopoietic cytokine designed to expand dendritic cells and HSCs.
For the study, researchers tested CDX-301 in sibling-matched donors for hematopoietic stem cell transplant (HSCT) recipients with hematologic malignancies.
The team reported early results with 4 donor/recipient pairs at the 2016 BMT Tandem Meetings (abstract 479). The research was sponsored by Celldex Therapeutics, Inc., the company developing CDX-301.
Donor results
The donors received CDX-301 at 75 μg/kg/day for 5 days. Leukapheresis began on day 6 if the peripheral blood CD34+ count was 7/μL or greater. The goal CD34+ yield was at least 2x106 per kilogram of recipient weight collected in 2 days of leukapheresis or less.
The donors could receive rescue plerixafor if the peripheral blood CD34+ count was less than 7/μL by day 8 or if the total CD34+ yield was less than 1x106/kg after the second day of leukapheresis.
The researchers analyzed CDX-301-mobilized cells by flow cytometry and compared them to historical data for peripheral blood grafts mobilized by granulocyte colony-stimulating factor (G-CSF).
Compared to the G-CSF-mobilized grafts, CDX-301-mobilized grafts had an increase in CD127+ (IL-7R) naïve T cells, γδ T cells, natural killer cells, and B cells.
The CDX-301-mobilized grafts were more enriched with plasmacytoid dendritic cells. And dendritic cells from the CDX-301 grafts had a more mature phenotype, expressing CD80 and CD86.
“From these data and preclinical studies, CDX-301 appears to be an effective, targeted approach to mobilization comparable to G-CSF,” said Steven Devine, MD, of The Ohio State Comprehensive Cancer Center in Columbus.
“With a relatively short course of treatment, we are observing specificity for mobilized stem cells and a lack of toxicity, instead of broad cellular mobilization and side effects.”
CDX-301 related adverse events included dizziness (grade 2), back pain (grade 1), arthralgia (grade 1), injection site reaction (2 grade 1), dyspepsia (1 grade 1, 1 grade 2), and decreased platelet count (2 grade 1). There were no grade 3/4 adverse events.
Recipient results
Thus far, 4 recipients have undergone HSCT with CDX-301-mobilized grafts. Recipient 1 had acute myeloid leukemia, recipients 2 and 3 had mantle cell lymphoma, and recipient 4 had chronic myeloid leukemia.
Recipients 1 through 3 received myeloablative conditioning, while recipient 4 received reduced-intensity conditioning. All patients received standard graft-vs-host disease (GVHD) prophylaxis (tacrolimus and methotrexate).
Recipient 4 has not yet engrafted. The other 3 had both neutrophil engraftment (day 17, 18, and 19) and platelet engraftment (day 14, 25, and 40).
There have been no infectious complications, and recipients 1 and 3 have not developed GVHD.
Recipient 2 developed steroid-responsive, grade 2, upper gastrointestinal GVHD on day 18, followed by grade 1 skin GVHD on day 50 that progressed to stage 3. Overall, the patient had grade 2 GVHD on day 64. The patient’s lymphoma has also progressed.
The researchers said these results suggest CDX-301 is well tolerated and can mobilize CD34+ cells when given as a single agent. They said recipients experienced successful engraftment in an expected time frame.
And the additional naïve T cells and plasmacytoid dendritic cells in CDX-301-mobilized grafts (compared to G-CSF-mobilized grafts) may provide better outcomes in HSCT recipients.
Now, the researchers plan to explore CDX-301 in combination with plerixafor. Additional donor/patient pairs are being accrued to a second study cohort.