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TRIAL OF AB-205 (E-CEL® CELLS) IN ADULTS WITH SYSTEMIC LYMPHOMA UNDERGOING HIGH-DOSE THERAPY AND AUTOLOGOUS HEMATOPOIETIC CELL TRANSPLANTATION (HDT-AHCT)RESULTS OF AB-205-001 BY AGE SUBGROUP
Author(s): ,
Mehrdad Abedi
Affiliations:
Hematology and Oncology,University of California Davis,Davis, CA,United States
,
Michael Scordo
Affiliations:
Medicine, Adult Bone Marrow Transplant Service,Memorial Sloan Kettering Cancer Center,New York,United States
,
Lihua E. Budde
Affiliations:
Hematology and Hematopoietic Cell Transplantation,City of Hope National Medical Center,Duarte, CA,United States
,
Carolyn Mulroney
Affiliations:
Medicine, Blood and Marrow Transplantation,University of California San Diego,San Diego,United States
,
Bita Fakhri
Affiliations:
Medicine, Blood and Marrow Transplantation,University of California San Francisco,San Francisco,United States
,
Attaphol Pawarode
Affiliations:
Medicine, Blood and Marrow Transplantation,University of Michigan,Ann Arbor,United States
,
Bhagirathbhai Dholaria
Affiliations:
Medicine, Division of Hematology and Oncology,Vanderbilt University,Nashville,United States
,
Edward Kavalerchik
Affiliations:
Clinical Development,Angiocrine Bioscience,San Diego,United States
,
Sanjay K. Aggarwal
Affiliations:
Clinical Development,Angiocrine Bioscience,San Diego,United States
,
Muzaffar Qazilbash
Affiliations:
Stem Cell Transplantation and Cellular Therapy,The University of Texas MD Anderson Cancer Center,Houston,United States
,
Paul Finnegan
Affiliations:
Clinical Development,Angiocrine Bioscience,San Diego,United States
Sergio Giralt
Affiliations:
Medicine, Adult Bone Marrow Transplant Service,Memorial Sloan Kettering Cancer Center,New York,United States
EHA Library. Abedi M. 06/09/21; 324955; EP1235
Mehrdad Abedi
Mehrdad Abedi
Contributions
Abstract
Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP1235

Type: E-Poster Presentation

Session title: Stem cell transplantation - Clinical

Background

Improvements in supportive care and HCT practices have led to increasing use of HDT-AHCT for patients with chemosensitive lymphomas, with a growing interest of treating older patients (pts). However, HDT is associated with high rates of severe regimen-related toxicities (SRRT), especially in older adults, (Dahi 2018) and the risk of life-threatening SRRT may preclude older pts or pts with co-morbidities from this potentially curative treatment.


SRRT is thought to result from diffuse injury to the microvasculature forming the organ vascular stem cell niches caused by off-target cytotoxic effects of HDT. SRRT involves virtually all organ systems, but is most evident in organs with high cell turnover such as  oral-gastrointestinal (oral/GI) tract and bone marrow. While the hematopoietic system is rescued by AHCT, there are no effective therapies to repair damage to other organs.


AB-205 is a novel experimental engineered-cell therapy. AB-205 contains E-CEL® cells: allogeneic E4+ human cord endothelial cells. E-CEL cells express multiple angiocrine factors in a dynamic, paracrine manner.

Aims
AB-205-001 objectives included assessing initial safety and efficacy.

Methods
Subjects with chemosensitive lymphomas eligible for HDT-AHCT were enrolled. AB-205 was administered IV after AHCT in dose-escalated cohorts: 5, 10 and 20x106 cells/kg, either as single or divided (D0, D2) dose. Supportive care therapies were administered as per site institutional guidelines. Oral/GI SRRT was defined as NCI-CTCAEv5.0 grade (G)≥3 oral mucositis, nausea, vomiting or diarrhea. A retrospective chart review (n=45) at a participating site served as a contemporary control.

Results

Overall results have been presented previously [ASH 2020, TCT 2021, EBMT 2021]. Here we present data from pts treated with  20x106 cells/kg by age.


29 systemic lymphoma subjects were treated with AB-205 with a median (range) follow up of 271 (179, 566) days. MTD was not reached. AEs were generally mild/moderate and as expected with HDT-AHCT.


AB-205 therapy demonstrated dose-dependent reduction of oral/GI SRRT. No (0%) oral/GI SRRT were reported for any subjects (n=18) receiving the recommended AB-205 dose, including the subjects ≥60 yo (n=7). In contrast, the control cohort reported 16/25 (64%) oral/GI SRRT rate ≥60 yo, while those <60 yo had 9/20 (45%).


Median time to neutrophil engraftment, platelet engraftment and number of hospitalization days (from AHCT) were numerically lower with AB-205 than in the control cohort by approximately 2, 7 and 3 days respectively (Table). The benefits with AB-205 treatment were consistent across age subgroups.


As of the cutoff date, there have been no reports of SRRT affecting the pulmonary, cardiac, renal or hepatic systems. No detrimental effect on PFS or OS was observed. There were no deaths by day 100.

Conclusion
20x106 cells/kg of AB-205 eliminated the occurrence of oral/GI SRRT including in subjects 60 yo. In contrast, 64% event rates were seen in pts ≥60 yo in a contemporary control cohort. AB-205 has potential to make HDT-AHCT substantially safer for older pts and may enable physicians to consider this potentially curative therapy for high-risk patients currently considered ineligible for HCT.

Keyword(s): Autologous hematopoietic stem cell transplantation, Cellular therapy, Lymphoma therapy, Supportive care

Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP1235

Type: E-Poster Presentation

Session title: Stem cell transplantation - Clinical

Background

Improvements in supportive care and HCT practices have led to increasing use of HDT-AHCT for patients with chemosensitive lymphomas, with a growing interest of treating older patients (pts). However, HDT is associated with high rates of severe regimen-related toxicities (SRRT), especially in older adults, (Dahi 2018) and the risk of life-threatening SRRT may preclude older pts or pts with co-morbidities from this potentially curative treatment.


SRRT is thought to result from diffuse injury to the microvasculature forming the organ vascular stem cell niches caused by off-target cytotoxic effects of HDT. SRRT involves virtually all organ systems, but is most evident in organs with high cell turnover such as  oral-gastrointestinal (oral/GI) tract and bone marrow. While the hematopoietic system is rescued by AHCT, there are no effective therapies to repair damage to other organs.


AB-205 is a novel experimental engineered-cell therapy. AB-205 contains E-CEL® cells: allogeneic E4+ human cord endothelial cells. E-CEL cells express multiple angiocrine factors in a dynamic, paracrine manner.

Aims
AB-205-001 objectives included assessing initial safety and efficacy.

Methods
Subjects with chemosensitive lymphomas eligible for HDT-AHCT were enrolled. AB-205 was administered IV after AHCT in dose-escalated cohorts: 5, 10 and 20x106 cells/kg, either as single or divided (D0, D2) dose. Supportive care therapies were administered as per site institutional guidelines. Oral/GI SRRT was defined as NCI-CTCAEv5.0 grade (G)≥3 oral mucositis, nausea, vomiting or diarrhea. A retrospective chart review (n=45) at a participating site served as a contemporary control.

Results

Overall results have been presented previously [ASH 2020, TCT 2021, EBMT 2021]. Here we present data from pts treated with  20x106 cells/kg by age.


29 systemic lymphoma subjects were treated with AB-205 with a median (range) follow up of 271 (179, 566) days. MTD was not reached. AEs were generally mild/moderate and as expected with HDT-AHCT.


AB-205 therapy demonstrated dose-dependent reduction of oral/GI SRRT. No (0%) oral/GI SRRT were reported for any subjects (n=18) receiving the recommended AB-205 dose, including the subjects ≥60 yo (n=7). In contrast, the control cohort reported 16/25 (64%) oral/GI SRRT rate ≥60 yo, while those <60 yo had 9/20 (45%).


Median time to neutrophil engraftment, platelet engraftment and number of hospitalization days (from AHCT) were numerically lower with AB-205 than in the control cohort by approximately 2, 7 and 3 days respectively (Table). The benefits with AB-205 treatment were consistent across age subgroups.


As of the cutoff date, there have been no reports of SRRT affecting the pulmonary, cardiac, renal or hepatic systems. No detrimental effect on PFS or OS was observed. There were no deaths by day 100.

Conclusion
20x106 cells/kg of AB-205 eliminated the occurrence of oral/GI SRRT including in subjects 60 yo. In contrast, 64% event rates were seen in pts ≥60 yo in a contemporary control cohort. AB-205 has potential to make HDT-AHCT substantially safer for older pts and may enable physicians to consider this potentially curative therapy for high-risk patients currently considered ineligible for HCT.

Keyword(s): Autologous hematopoietic stem cell transplantation, Cellular therapy, Lymphoma therapy, Supportive care

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