Taewoong Choi

Overview:

Based on my prior experience in basic/translational immunology research and clinical hematopoietic stem cell transplantation, I am interested in early phase clinical protocols for novel immunotherapy of hematologic malignancies.

Positions:

Assistant Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2002

Seoul National University (South Korea)

Internship and Residency in Internal Medicine

St. Luke's Memorial Hospital Center

Hematology/Oncology Fellowship

University of Pittsburgh, School of Medicine

BMT Fellowship

Stanford University, School of Medicine

Postdoctoral Research Fellow on T32 Training Grant

Stanford University, School of Medicine

Grants:

Prospective, Multicenter, Open-Label, Single Arm, Phase 2 Study to Evaluate the Safety and Efficacy of Defibrotide in the Prevention of Chimeric Antigen Receptor-T-cell-associated Neurotoxicity in Subjects with Relapsed or Refractory Diffuse Large B-

Administered By
Duke Cancer Institute
Awarded By
Jazz Pharmaceuticals
Role
Principal Investigator
Start Date
End Date

A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of BB2121 Versus Standard Triplet Regimens in Subjects with Relapsed and Refractory Multiple Myeloma (RRMM) (KARMMa-3)

Administered By
Duke Cancer Institute
Awarded By
Celgene Corporation
Role
Principal Investigator
Start Date
End Date

A Phase I, Open-Label, Multi-Center, Dose Escalation and Dose Expansion Study of NKTR-255 as a single agent in relapsed or refractory hematological malignancies and in combgination with Daratumumab as a Salvage Regimen for Multiple Myeloma

Administered By
Duke Cancer Institute
Awarded By
Nektar Therapeutics
Role
Principal Investigator
Start Date
End Date

Long Term Follow-up Protocol for Subjects Treated with Gene-Modified T Cells

Administered By
Duke Cancer Institute
Awarded By
Celgene Corporation
Role
Principal Investigator
Start Date
End Date

A Phase 3 Randomized Study Comparing JNJ-68284528, a Chimeric Antigen Receptor T cell (CAR-T) Therapy Directed Against BCMA, versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd)

Administered By
Duke Cancer Institute
Awarded By
Janssen Research & Development, LLC
Role
Principal Investigator
Start Date
End Date

Publications:

Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma.

Although treatment outcomes of multiple myeloma patients have improved significantly during the last two decades, myeloma is still an incurable disease. There are newly emerging immunotherapies to treat multiple myeloma including monoclonal antibodies, antibody-drug conjugate, bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy. Impressive response rate and clinical efficacy in heavily pretreated myeloma patients led to the FDA approval of the first myeloma CAR-T therapy in March 2021. Among many different targets for myeloma CAR-T therapies, B Cell Maturation Antigen (BCMA) has been the most successful target so far, but other targets which can be used either for single-target or dual-target CAR-T's are actively being explored. Clinical efficacy and safety of current myeloma CAR-T therapies will be presented here. Potential mechanisms leading to resistance include clearance of CAR-T cells, antigenic escape, and immunosuppressive tumor microenvironment. Novel strategies to enhance myeloma CAR-T will also be described. In this article, we provide a comprehensive review of the current data and the future directions of myeloma CAR-T therapies.
Authors
MLA Citation
Choi, Taewoong, and Yubin Kang. “Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma.Pharmacol Ther, Sept. 2021, p. 108007. Pubmed, doi:10.1016/j.pharmthera.2021.108007.
URI
https://scholars.duke.edu/individual/pub1497860
PMID
34582835
Source
pubmed
Published In
Pharmacol Ther
Published Date
Start Page
108007
DOI
10.1016/j.pharmthera.2021.108007

Obesity-Independent Association between Glycemic Status and the Risk of Hematologic Malignancy: A Nationwide Population-Based Longitudinal Cohort Study.

There have been conflicting results regarding the association between diabetes and the risk of hematologic malignancies, and its interaction with obesity is unknown. This study determined the risk of hematologic malignancies according to the glycemic status in a population-based study involving health screening 9,774,625 participants. The baseline glycemic status of the participants was categorized into no diabetes, impaired fasting glucose (IFG), newly detected diabetes, diabetes duration <5 years, and diabetes duration ≥5 year groups. The risks of overall and specific hematologic malignancies were estimated using a Cox regression analysis. During a median follow up of 7.3 years, 14,733 hematologic malignancies developed. The adjusted hazard ratio (aHR) for the risk of all the hematologic malignancies was 0.99 (95% confidence interval (CI) 0.95-1.02) for IFG, 0.99 (95% CI 0.91-1.08) for newly detected diabetes, 1.03 (95% CI 0.96-1.11) for diabetes duration <5 years, and 1.11 (95% CI 1.03, 1.20) for diabetes duration ≥5 year groups. The association was independent from obesity. The risk of non-Hodgkin's lymphoma (NHL) increased according to the progression of dysglycemia towards a longer diabetes duration, while Hodgkin's lymphoma did not. This study in Korea demonstrated diabetes to be associated with an increased risk of hematologic malignancies independent of obesity. The NHL risk increased with the diabetes duration.
Authors
Kang, J; Jin, S-M; Kim, SJ; Kim, D; Han, K; Jeong, S-M; Chang, J; Rhee, SY; Choi, T; Shin, DW
MLA Citation
Kang, Jihun, et al. “Obesity-Independent Association between Glycemic Status and the Risk of Hematologic Malignancy: A Nationwide Population-Based Longitudinal Cohort Study.Cancers (Basel), vol. 13, no. 19, Sept. 2021. Pubmed, doi:10.3390/cancers13194760.
URI
https://scholars.duke.edu/individual/pub1497895
PMID
34638244
Source
pubmed
Published In
Cancers
Volume
13
Published Date
DOI
10.3390/cancers13194760

Female Sex Is Associated with Improved Long-Term Survival Following Allogeneic Hematopoietic Stem Cell Transplantation.

Life expectancy for long-term survivors of allogeneic hematopoietic stem cell transplantation (alloHSCT), defined as those living ≥5 years post-transplantation, is significantly lower compared with that of the age-matched general population despite a relatively low primary disease relapse rate at >2 years post-transplantation. Among several factors, patient sex is increasingly recognized as a prognostic indicator of long-term survival. We examined the influence of patient sex and donor-recipient sex matching on overall survival (OS) in a landmark analysis of long-term survivors. Using our institutional database supplemented with individual patient record review, we retrospectively investigated the relative influence of recipient sex and donor-recipient sex matching on outcomes of long-term survivors of alloHSCT between 1994 and 2014. Over this 20-year period, 247 met inclusion criteria for analysis; males and females had similar demographic and treatment characteristics. However, significantly more deaths after the 5-year landmark occurred in male recipients. Interestingly, donor sex did not have a significant impact on OS in multivariate analysis, and differences in OS of donor-recipient sex pairs was driven by recipient sex. In addition to recipient sex, only chronic graft-versus-host disease (cGVHD) retained significance as a covariate with an impact on OS in multivariate analysis. Men experienced slightly higher, but statistically nonsignificant, rates and increased severity of cGVHD, and had higher cGVHD-related mortality compared with females. In this long-term survival analysis of adult alloHSCT recipients, one of the only to include follow-up to 15 years, our results show that women survive significantly longer than men irrespective of their age at transplantation. This outcome is independent of other common pretransplantation prognostic indicators, such as donor sex or performance status at transplantation. The inferior survival in males is consistent with survival outcomes described in the transplantation literature. Increasing evidence suggests a biological basis for long-term sex-determined outcomes, possibly owing to differing rates or severity of cGVHD or sustained alloimmune tolerance in females. Larger studies are warranted to validate these retrospective clinical results.
Authors
Islam, P; Tang, H; Jin, H; Cao, F; Bohannon, LM; Ren, Y; Chao, NJ; Choi, T; Gasparetto, C; Horwitz, ME; Long, GD; Lopez, RD; Rizzieri, DA; Sarantopoulos, S; Sung, AD
MLA Citation
Islam, Prioty, et al. “Female Sex Is Associated with Improved Long-Term Survival Following Allogeneic Hematopoietic Stem Cell Transplantation.Transplant Cell Ther, vol. 27, no. 9, Sept. 2021, pp. 784.e1-784.e7. Pubmed, doi:10.1016/j.jtct.2021.06.012.
URI
https://scholars.duke.edu/individual/pub1485675
PMID
34146734
Source
pubmed
Published In
Transplant Cell Ther
Volume
27
Published Date
Start Page
784.e1
End Page
784.e7
DOI
10.1016/j.jtct.2021.06.012

Decreased Mortality in 1-Year Survivors of Umbilical Cord Blood Transplant vs. Matched Related or Matched Unrelated Donor Transplant in Patients with Hematologic Malignancies.

Allogeneic hematopoietic stem cell transplantation (HCT) has the potential to cure hematologic malignancies but is associated with significant morbidity and mortality. Although deaths during the first year after transplantation are often attributable to treatment toxicities and complications, death after the first year may be due to sequelae of accelerated aging caused by cellular senescence. Cytotoxic therapies and radiation used in cancer treatments and conditioning regimens for HCT can induce aging at the molecular level; HCT patients experience time-dependent effects, such as frailty and aging-associated diseases, more rapidly than people who have not been exposed to these treatments. Consistent with this, recipients of younger cells tend to have decreased markers of aging and improved survival, decreased graft-versus-host disease, and lower relapse rates. Given that umbilical cord blood (UCB) is the youngest donor source available, we studied the outcomes after the first year of UCB transplantation versus matched related donor (MRD) and matched unrelated donor (MUD) transplantation in patients with hematologic malignancies over a 20-year period. In this single-center, retrospective study, we examined the outcomes of all adult patients who underwent their first allogeneic HCT through the Duke Adult Bone Marrow Transplant program from January 1, 1996, to December 31, 2015, to allow for at least 3 years of follow-up. Patients were excluded if they died or were lost to follow-up before day 365 after HCT, received an allogeneic HCT for a disease other than a hematologic malignancy, or received cells from a haploidentical or mismatched adult donor. UCB recipients experienced a better unadjusted overall survival than MRD/MUD recipients (log rank P = .03, median overall survival: UCB not reached, MRD/MUD 7.4 years). After adjusting for selected covariates, UCB recipients who survived at least 1 year after HCT had a hazard of death that was 31% lower than that of MRD/MUD recipients (hazard ratio, 0.69; 95% confidence interval, 0.47-0.99; P = .049). This trend held true in a subset analysis of subjects with acute leukemia. UCB recipients also experienced lower rates of moderate or severe chronic graft-versus-host disease (GVHD) and nonrelapse mortality, and slower time to relapse. UCB and MRD/MUD recipients experienced similar rates of grade 2-4 acute GVHD, chronic GHVD, secondary malignancy, and subsequent allogeneic HCT. UCB is already widely used as a donor source in pediatric HCT; however, adult outcomes and adoption have historically lagged behind in comparison. Recent advancements in UCB transplantation such as the implementation of lower-intensity conditioning regimens, double unit transplants, and ex vivo expansion have improved early mortality, making UCB an increasingly attractive donor source for adults; furthermore, our findings suggest that UCB may actually be a preferred donor source for mitigating late effects of HCT.
Authors
Bohannon, L; Tang, H; Page, K; Ren, Y; Jung, S-H; Artica, A; Britt, A; Islam, P; Siamakpour-Reihani, S; Giri, V; Lew, M; Kelly, M; Choi, T; Gasparetto, C; Long, G; Lopez, R; Rizzieri, D; Sarantopoulos, S; Chao, N; Horwitz, M; Sung, A
MLA Citation
Bohannon, Lauren, et al. “Decreased Mortality in 1-Year Survivors of Umbilical Cord Blood Transplant vs. Matched Related or Matched Unrelated Donor Transplant in Patients with Hematologic Malignancies.Transplant Cell Ther, vol. 27, no. 8, Aug. 2021, pp. 669.e1-669.e8. Pubmed, doi:10.1016/j.jtct.2021.05.002.
URI
https://scholars.duke.edu/individual/pub1482829
PMID
33991725
Source
pubmed
Published In
Transplant Cell Ther
Volume
27
Published Date
Start Page
669.e1
End Page
669.e8
DOI
10.1016/j.jtct.2021.05.002

A phase 2 trial of the somatostatin analog pasireotide to prevent GI toxicity and acute GVHD in allogeneic hematopoietic stem cell transplant.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HCT) is an often curative intent treatment, however it is associated with significant gastrointestinal (GI) toxicity and treatment related mortality. Graft-versus-host disease is a significant contributor to transplant-related mortality. We performed a phase 2 trial of the somatostatin analog pasireotide to prevent gastrointestinal toxicity and GVHD after myeloablative allogeneic HCT. METHODS: Patients received 0.9mg pasireotide every 12 hours from the day prior to conditioning through day +4 after HCT (or a maximum of 14 days). The primary outcomes were grade 3-4 gastrointestinal toxicity through day 30 and acute GVHD. Secondary outcomes were chronic GVHD, overall survival and relapse free survival at one year. Stool and blood samples were collected from before and after HCT for analyses of stool microbiome, local inflammatory markers, and systemic inflammatory and metabolic markers. Results were compared with matched controls. RESULTS: Twenty-six patients received pasireotide and were compared to 52 matched contemporaneous controls using a 1-2 match. Grade 3-4 GI toxicity occurred in 21 (81%) patients who received pasireotide and 35 (67%) controls (p = 0.33). Acute GVHD occurred in 15 (58%) patients in the pasireotide group and 28 (54%) controls (p = 0.94). Chronic GVHD occurred in 16 patients in the pasireotide group (64%) versus 22 patients in the control group (42%) (p = 0.12). Overall survival at 1 year in the pasireotide group was 63% (95% CI: 47%,86%) versus 82% (95% CI: 72%, 93%) in controls (log-rank p = 0.006). Relapse-free survival rate at one year was 40% (95% CI: 25%, 65%) in the pasireotide group versus 78% (95% CI: 68%, 91%) in controls (log-rank p = 0.002). After controlling for the effect of relevant covariates, patients in the pasireotide group had attenuated post-HCT loss of microbial diversity. Analysis of systemic inflammatory markers and metabolomics demonstrated feasibility of such analyses in patients undergoing allogeneic HCT. Baseline level and pre-to-post transplant changes in several inflammatory markers (including MIP1a, MIP1b, TNFa, IL8Pro, and IL6) correlated with likelihood of survival. CONCLUSIONS: Pasireotide did not prevent gastrointestinal toxicity or acute GVHD compared to contemporaneous controls. Pasireotide was associated with numerically higher chronic GVHD and significantly decreased OS and RFS compared to contemporaneous controls. Pasireotide may provide a locally protective effect in the stool microbiome and in local inflammation as measured by stool calprotectin, stool beta-defensin, and stool diversity index.
Authors
Ramalingam, S; Siamakpour-Reihani, S; Bohannan, L; Ren, Y; Sibley, A; Sheng, J; Ma, L; Nixon, AB; Lyu, J; Parker, DC; Bain, J; Muehlbauer, M; Ilkayeva, O; Kraus, VB; Huebner, JL; Spitzer, T; Brown, J; Peled, JU; van den Brink, M; Gomes, A; Choi, T; Gasparetto, C; Horwitz, M; Long, G; Lopez, R; Rizzieri, D; Sarantopoulos, S; Chao, N; Sung, AD
MLA Citation
Ramalingam, Sendhilnathan, et al. “A phase 2 trial of the somatostatin analog pasireotide to prevent GI toxicity and acute GVHD in allogeneic hematopoietic stem cell transplant.Plos One, vol. 16, no. 6, 2021, p. e0252995. Pubmed, doi:10.1371/journal.pone.0252995.
URI
https://scholars.duke.edu/individual/pub1487527
PMID
34170918
Source
pubmed
Published In
Plos One
Volume
16
Published Date
Start Page
e0252995
DOI
10.1371/journal.pone.0252995

Research Areas:

Cellular therapy
Immunotherapy
Multiple Myeloma
Plasma cell diseases
Stem Cell Transplantation