Yubin Kang's research while affiliated with Duke University and other places

Publications (92)

Preprint
Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, we compared the transcriptomic and chromatin accessibility landscapes of six matched sets of colorectal...
Article
Many patients with multiple myeloma (MM) have comorbidities and are treated with PPAR agonists. Immunomodulatory agents (IMiDs) are the cornerstones for MM therapy. Currently, little is known about how co-administration of PPAR agonists impacts lenalidomide treatment in patients with MM. Here, we determined the effects of PPAR agonists on anti-myel...
Article
Full-text available
The United States is undergoing a demographic shift towards an older population with profound economic, social, and healthcare implications. The number of Americans aged 65 and older will reach 80 million by 2040. The shift will be even more dramatic in the extremes of age, with a projected 400% increase in the population over 85 years old in the n...
Article
Full-text available
Background: Anaplastic multiple myeloma (AMM) is a very rare but distinct subtype of multiple myeloma (MM) with an extremely poor prognosis. Due to its rarity, AMM lacks detailed descriptions and clear definitions. Moreover, there is no consensus on the treatment and evidence suggests that AMM responds poorly to several novel therapies. We conduct...
Article
The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, initial workup, treatment, follow-up, and supportive care for patients with various plasma cell neoplasms, including multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates/changes specific to the treatment of patients with multiple myel...
Article
Background: MM that is refractory to a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 monoclonal antibody (CD38MoAb) is labeled triple-class refractory (TCR) and recognized as a modern therapeutic challenge. In recent years, new agents have shown activity in this setting in single arm trials and many more are in develo...
Article
Background Despite high efficacy of three main classes of anti-myeloma agents, i.e., proteasome inhibitors (PI), immunomodulatory agents (IMiD) and anti-CD38 monoclonal antibodies (CD38MoAb), Multiple Myeloma (MM) remains incurable; therefore clinical trials testing new agents in the relapsed setting are crucial to open new therapeutic avenues. Whe...
Article
Full-text available
Myeloid-derived suppressor cells (MDSCs) are a hetero geneous group of cells, which can suppress the immune response, promote tumor progression and impair the efficacy of immunotherapies. Consequently, the pharmacological targeting of MDSC is emerging as a new immunotherapeutic strategy to stimulate the natural anti-tumor immune response and potent...
Article
Background : In the single-arm, phase 1b/2 CARTITUDE-1 study, ciltacabtagene autoleucel (cilta-cel), an anti-B-cell maturation antigen chimeric antigen receptor T-cell (CAR-T) therapy, showed encouraging efficacy in US patients with multiple myeloma (MM) who previously received an immunomodulatory drug, proteasome inhibitor, and anti-CD38 monoclona...
Article
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 therap...
Article
Multiple myeloma (MM) remains an incurable disease and novel therapeutic agents/approaches are urgently needed. The PIM (Proviral insertion in murine malignancies) serine/threonine kinases have 3 isoforms: PIM1, PIM2, and PIM3. PIM kinases are engaged with an expansive scope of biological activities including cell growth, apoptosis, drug resistance...
Preprint
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells, which can suppress the immune response, promote tumor progression and impair the efficacy of immunotherapies. Consequently, the pharmacological targeting of MDSC is emerging as a new immunotherapeutic strategy to stimulate the natural anti-tumor immune response and potenti...
Article
8030 Background: CARTITUDE-1 is a single arm study of Ciltacabtagene autoleucel (cilta-cel; JNJ-68284528) anti-BCMA CAR-T cell therapy in US patients (pts) with relapsed multiple myeloma (RRMM) refractory to both IMiD and proteasome inhibitor (PI) or with at least 3 prior lines of therapy and previously exposed to anti-CD38 monoclonal antibody (MoA...
Article
Full-text available
Prophylactic donor lymphocyte infusions (DLI) are used to augment post-transplant immune recovery to reduce both infectious complications and disease recurrence. Preclinical studies implicate the naive T-cell subset as the primary driver of graft-versus-host disease (GvHD). In this phase I dose escalation study, we assessed the safety of a DLI that...
Article
Multiple myeloma is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. This manuscript discusses the management of patients with solitary plasmacytoma, smoldering multiple myeloma, and newly diagnosed multiple myeloma.
Article
Full-text available
We determined the impact of bone marrow fibrosis (BMF) on the clinical outcomes of newly diagnosed multiple myeloma (NDMM) patients in the current era of myeloma therapy. A total of 393 MM patients were included in the final analysis. The median followup was 83 months (range: 3.9 to 212 months). BMF was noted in 122 (48.2%) evaluable patients. Medi...
Article
Full-text available
A window to the embryo Mammalian embryonic development is a complex process, continuously changing in space and time. Q. Huang et al. designed an abdominal window to image mouse embryos in utero from embryonic day 9.5 to birth. Using this technique, they visualized dynamic activities during embryonic organ formation, including neurotransmission and...
Article
PURPOSE We performed a retrospective chart review on 393 patients with multiple myeloma (MM) to determine the utility of the gamma gap (GG). METHODS We calculated the difference between a patient’s total serum protein and albumin as a point-of-care test for assessing disease status in MM. RESULTS GG is highly correlated with the level of M-spike,...
Article
Full-text available
The roles of mitochondrial dysfunction in carcinogenesis remain largely unknown. The effects of PTEN‐induced putative kinase 1 (PINK1)‐dependent mitophagy on the pathogenesis of multiple myeloma (MM) are determined. The levels of the PINK1‐dependent mitophagy markers PINK1 and parkin RBR E3 ubiquitin protein ligase (PARK2) in CD138+ plasma cells ar...
Article
Introduction: Proteasome inhibitors (PI), immunomodulatory agents (IMiDs) and the CD38 monoclonal antibody daratumumab (dara) have transformed the management of MM, yet eventual refractoriness to these agents seems inevitable. Relapsed and refractory MM (RRMM) which becomes triple class refractory (TCR, i.e. refractory to a PI, an IMiD and Dara) un...
Article
The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, workup, treatment, follow-up, and supportive care for patients with monoclonal gammopathy of renal significance, solitary plasmacytoma, smoldering myeloma, and multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates and changes in the 1....
Article
Full-text available
The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients at 14 academic centers with disease refractory to...
Article
A cure for multiple myeloma (MM), a malignancy of plasma cells, remains elusive. Nearly all myeloma patients will eventually relapse and develop resistance to currently available treatments. There is an unmet medical need to develop novel and effective therapies that can induce sustained responses. Early phase clinical trials using chimeric antigen...
Article
e19514 Background: The treatment of newly diagnosed multiple myeloma (NDMM) has evolved significantly with the advent of the immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs). While the presence of bone marrow fibrosis (BMF) has previously been associated with poor prognosis in multiple myeloma (MM), these studies were small and condu...
Article
Full-text available
Metabolism is defined as the collection of complex biochemical processes that living cells use to generate energy and maintain their growth and survival. Metabolism encompasses the synthesis and breakdown of glucose, fatty acids, and amino acids; the generation of energy (ATP); and oxidative phosphorylation. In cancer cells, metabolism can be comma...
Article
Full-text available
Introduction Prophylactic, donor lymphocyte infusion (DLI) is used to augment immune recovery and graft vs. tumor effect following a T-cell depleted alloSCT. However, it carries the risk of inducing severe GvHD. Our pre-clinical murine studies have implicated the naive T-cell, defined by CD62L marker, as the primary driver of alloreactivity. We hyp...
Article
Introduction: Monoclonal antibodies (MoAbs) have shown activity in relapsed and refractory multiple myeloma (MM). Elotuzumab is an anti-SLAMF7 MoAb that synergizes with immunomodulatory agents (IMiDs) and is approved for treatment of relapsed and refractory MM. Anti-CD38 MoAbs (daratumumab, FDA approved and isatuximab, in clinical trials) have also...
Article
Introduction Development of anti-CD38 monoclonal antibody therapies (MoABs), including daratumumab and isatuximab, have drastically changed the therapeutic landscape for management of relapsed and/or refractory multiple myeloma (RRMM). However, there is a paucity of information regarding response to treatment after progression on CD38 MoABs. This c...
Article
Introduction Proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) have significantly improved survival in patients with multiple myeloma (MM). Refractoriness to PIs and IMiDs results in poor outcomes with a median survival of about 13 months.Daratumumab and isatuximab are CD38-targeting monoclonal antibodies (MoABs) with remarkable activi...
Article
Multiple myeloma remains an incurable disease, and continued efforts are required to develop novel agents and novel drug combinations with more effective anti-myeloma activity. Here, we show that the pan-PIM kinase inhibitors SGI1776 and CX6258 exhibit significant anti-myeloma activity and that combining a pan-PIM kinase inhibitor with the immunomo...
Article
Despite significant improvements in the overall survival of patients with multiple myeloma (MM) over the past 15 years, the disease remains incurable. Treatment options are limited for patients who have relapsed or are refractory to immunomodulatory drugs (IMiDs), proteasome inhibitors, and monoclonal antibodies. In these patients, immunotherapies...
Article
Full-text available
Multiple myeloma (MM) remains an incurable disease in need of the development of novel therapeutic agents and drug combinations. ABT‐199 is a specific Bcl‐2 inhibitor in clinical trials for MM; however, its activity as a single agent was limited to myeloma patients with the t(11;14) translocation who acquire resistance due to co‐expression of Mcl‐1...
Article
Full-text available
Background: Although current chemotherapy using bortezomib (Velcade) against multiple myeloma in adults has achieved significant responses and even remission, a majority of patients will develop acquired resistance to bortezomib. Increased thioredoxin level has been reported to be associated with carcinogenesis; however, the role of thioredoxin in...
Article
Full-text available
Single agent high-dose melphalan (HDM, 200 mg/m2) followed by autologous stem cell transplantation has been the most commonly used conditioning regimen since its introduction in 1992. We used a more aggressive alkylator based conditioning regimen in attempt to overcome early relapse and combat drug resistance. We present a retrospective comparison...
Article
The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, evaluation, treatment, including supportive-care, and follow-up for patients with myeloma. These NCCN Guidelines Insights highlight the important updates/changes specific to the myeloma therapy options in the 2018 version of the NCCN Guidelines.
Data
Track(s): Hematologic Malignancies—Plasma Cell Dyscrasia Phase I/II Dose Expansion of a Trial Investigating Bendamustine and Pomalidomide with Dexamethasone (Ben-Pom-d) In Patients With Relapsed/Refractory Multiple Myeloma - American Society of Clinical Oncology (ASCO 2017) - Oral Presentation (Hematologic Malignancies - Plasma Cell Dyscrasia 9:...
Article
Full-text available
Background Radiation exposure poses a significant threat to public health. Hematopoietic injury is one of the major manifestations of acute radiation sickness. Protection and/or mitigation of hematopoietic stem cells (HSCs) from radiation injury is an important goal in the development of medical countermeasure agents (MCM). We recently identified t...
Presentation
Full-text available
Phase I/II dose expansion of a trial investigating bendamustine and pomalidomide with dexamethasone (BPd) in patients with relapsed/refractory multiple myeloma
Article
8008 Background: The combination of bendamustine, pomalidomide, and dexamethasone (BPd) displays promising activity in heavily pretreated RRMM. In the Phase I portion, MTD was 120 mg/m ² bendamustine/3mg pomalidomide/40mg dexamethasone. We report our combined findings from the additional phase II expansion cohort for the first phase I/II trial of B...
Article
Objectives: Multiple myeloma (MM) primarily strikes older adults, but full-dose chemotherapy such as bortezomib (Velcade), cyclophosphamide and dexamethasone (VCD) is often excessively toxic to very old or frail adults and those with substantial comorbidities. We piloted dose-attenuated VCD ("VCD-Lite") in such vulnerable adults with newly diagnos...
Article
Full-text available
Background Receptor tyrosine kinase, c-Kit (CD117) plays a pivotal role in the maintenance and expansion of hematopoietic stem/progenitor cells (HSPCs). Additionally, over-expression and/or mutational activation of c-Kit have been implicated in numerous malignant diseases including acute myeloid leukemia. However, the translational regulation of c-...
Article
Full-text available
Comprehensive recommendations for maintenance therapy post-autologous stem cell transplantation (ASCT) for patients with multiple myeloma (MM) have yet to be defined. Bortezomib has been utilized as maintenance therapy after ASCT, but data attesting to the safety and efficacy of this agent compared to lenalidomide in the post-ASCT setting are limit...
Article
Full-text available
Background The binding of CXCR4 with its ligand (stromal-derived factor-1) maintains hematopoietic stem/progenitor cells (HSPCs) in a quiescent state. We hypothesized that blocking CXCR4/SDF-1 interaction after hematopoietic stem cell transplantation (HSCT) promotes hematopoiesis by inducing HSC proliferation. Methods We conducted a phase I/II tria...
Article
Background Bendamustine, a bifunctional mechlorethamine derivative with alkylating properties and pomalidomide, an IMiD® immunomodulatory agent, have both demonstrated efficacy as single agents or in combination with dexamethasone in relapsed/refractory multiple myeloma(RRMM). Bendamustine in combination with lenalidomide, thalidomide, and bortezom...
Article
Amyloidosis refers to a group of widely diverse conditions characterized by the deposition of insoluble protein within the extracellular space, leading to disruption of normal organ function. AL primary amyloidosis is associated with plasma cell dyscrasias and is caused by the deposition of insoluble kappa or lambda light chains. Cardiac involvemen...
Article
Introduction: The optimal treatment approach for systemic AL amyloidosis remains unclear. Autologous stem cell transplant (ASCT) is the only modality associated with long term survival, but failure to show survival benefit in randomized clinical trial raises doubts about its efficacy 1, 2. Outcomes after ASCT are better in patients who achieve comp...
Article
Full-text available
Sphingolipid metabolism is being increasingly recognized as a key pathway in regulating cancer cell survival and proliferation. However, very little is known about its role in multiple myeloma (MM). We investigated the potential of targeting sphingosine kinase 2 (SK2) for the treatment of MM. We found that SK2 was overexpressed in MM cell lines and...
Article
Thioredoxin (Trx) is an inflammation-inducible small oxidoreductase protein ubiquitously expressed in all organisms. Trx acts both intracellularly and extracellularly and is involved in a wide range of physiological cellular responses. Inside the cell, Trx alleviates oxidative stress by scavenging reactive oxygen species (ROS), regulates a variety...
Article
Background Compared with growth factor (G) alone, the combination of G with plerixafor (G + P) increases peripheral blood CD34+ count (PB-CD34+) and improves CD34+ collection yield (yCD34+) in multiple myeloma and lymphoma patients undergoing autologous hematopoietic progenitor cell (AHPC) mobilization. It is unknown whether the improved yCD34+ wit...
Article
Full-text available
: Multiple Myeloma (MM) is a debilitating disease of proliferating and malignant plasma cells that is currently incurable. The ability of monoclonal recurrence of disease suggests it might arise from a stem cell-like population capable of self-renewal. The difficulty to isolate the cancer stem-like cell in MM has introduced confusion toward this hy...
Article
Background Compared with growth factor (G) alone, the combination of G with the CXCR4 inhibitor plerixafor (G+P) increases peripheral blood CD34+ count and improves s CD34+ collection in multiple myeloma (MM) and lymphoma (Ly) patients undergoing autologous hematopoietic stem cell (AHSC) mobilization. It is unknown whether the improved CD34+ collec...
Article
Introduction Multiple Myeloma (MM) is the second most common hematological malignancy in the United States and accounts for ∼10,600 deaths annually. MM remains an incurable disease and almost all patients will eventually relapse and become refractory to currently available therapeutic agents. There is an unmet need for better understanding of the d...
Article
Background The alkylating agent melphalan, given at the myeloablative dose of 200mg/m2 preceding autologous hematopoietic stem cell transplantation (AHSCT), is part of the upfront management of patients with multiple myeloma (MM) and has been used in the salvage setting, often as second transplant. Proteasome inhibitors (PI) have been shown in vitr...
Article
Full-text available
It is unknown whether clinical characteristics can successfully predict which multiple myeloma (MM) patients would be poor mobilizers (PM) with growth factor (GF) alone so they can be assigned to mobilization with chemotherapy + GF or GF + plerixafor. MM patients (N=477) who underwent autologous mobilization with GF were retrospectively reviewed an...
Article
Hematopoiesis is regulated by the bone marrow (BM) niche microenvironment. We recently found that post transplant administration of AMD3100 (a specific and reversible CXCR4 antagonist) enhanced donor cell engraftment and promoted recovery of all donor cell lineages in a congeneic mouse transplant model. We hypothesized that AMD3100 enhances donor c...