About

Adam Cuker, MD, MS, is a Professor of Medicine (Hematology-Oncology) at the Hospital of the University of Pennsylvania and holds multiple leadership roles within the institution. He serves as the Assistant Director of the Specialized Coagulation Laboratory at the Hospital of the University of Pennsylvania, Associate Director of Clinical Research at the Penn-CHOP Blood Center for Patient Care and Discovery, and Clinical Director of the Penn Blood Disorders Center. Additionally, he is the Director of the Penn Comprehensive Hemophilia and Thrombosis Program and the Section Chief of Benign Hematology in the Division of Hematology/Oncology at the Perelman School of Medicine. His clinical expertise focuses on clotting disorders, bleeding disorders, and platelet disorders. His research expertise includes heparin-induced thrombocytopenia, immune thrombocytopenia, thrombosis, anticoagulation, platelet disorders, and bleeding disorders. Dr. Cuker has contributed to the understanding and diagnosis of heparin-induced thrombocytopenia, immune thrombocytopenia, and the management of anticoagulation in patients with major bleeding. His work includes the development of novel diagnostic assays and the investigation of mechanisms underlying thrombocytopenia and thrombosis, with numerous publications in these areas.

Research topics

• Internal medicine
• Medicine
• Intensive care medicine
• Cardiology
• Pathology

Selected publications

• Expert Opinion on Implementing Oral Anticoagulation Reversal Protocols in US Hospitals

  Clinical and Applied Thrombosis/Hemostasis · 2026-01-01

  articleOpen access

  Oral anticoagulants (OACs), including vitamin K antagonists and direct-acting OACs, are commonly used for the prevention and treatment of thrombosis. OAC-treated patients may require urgent anticoagulation reversal in circumstances of life-threatening bleeding or emergent surgery. Despite the availability of Food and Drug Administration-approved OAC reversal agents, published treatment guidelines, and institutional protocols, use of OAC reversal products and dosing vary considerably and off-label use is common. We review key factors influencing current clinical practice and examine barriers to the successful implementation of anticoagulation protocols, including discrepancies in the definition of major bleeding, dosing considerations, variability in laboratory testing practices, inconsistent study endpoints, formulary considerations, and the use of OAC reversal agents in special populations. We provide our expert opinion on best practices for oral anticoagulant reversal and an anticoagulation reversal protocol that could be implemented by healthcare institutions to standardize and optimize clinical practice.

  PublisherDOI

• Health-related quality of life in adults with hemophilia B after gene therapy with fidanacogene elaparvovec: results from the BENEGENE-2 trial

  Journal of Thrombosis and Haemostasis · 2025-10-18 · 2 citations

  article
  PublisherDOI

• Ianalumab plus Eltrombopag in Immune Thrombocytopenia

  New England Journal of Medicine · 2025-12-09

  article1st authorCorresponding

  BACKGROUND: Current second-line treatments for immune thrombocytopenia (ITP) require long-term administration. Ianalumab, a monoclonal antibody targeting B cells, is being assessed as a short-course second-line therapy in ITP. METHODS: per liter in at least 75% of the measurements between weeks 19 and 25 without use of rescue therapy or new ITP therapy. Safety was assessed. RESULTS: A total of 152 patients underwent randomization: 50 to the 9-mg ianalumab group, 51 to the 3-mg ianalumab group, and 51 to the placebo group. The estimated probability of being free from treatment failure at 12 months was 54% (95% confidence interval [CI], 39 to 67) in the 9-mg group, 51% (95% CI, 36 to 64) in the 3-mg group, and 30% (95% CI, 18 to 43) in the placebo group. The time to treatment failure was significantly longer with ianalumab plus eltrombopag than with placebo plus eltrombopag; the estimated hazard ratio for treatment failure (ianalumab vs. placebo) was 0.55 (P = 0.04) in the 9-mg group and 0.58 (P = 0.045) in the 3-mg group. The percentage of patients with a stable response at 6 months was significantly higher in the 9-mg group than in the placebo group (62% vs. 39%; P = 0.045). The overall frequency of adverse events during the treatment period was generally similar in the three groups. The frequency of serious adverse events was 16% in the 9-mg group, 6% in the 3-mg group, and 4% in the placebo group. CONCLUSIONS: Ianalumab plus eltrombopag led to a longer time to treatment failure than placebo plus eltrombopag. (Funded by Novartis; VAYHIT2 ClinicalTrials.gov number, NCT05653219.).

  PublisherDOI

• HTRS2025.P2.54 Corticosteroid Experience With Fidanacogene Elaparvovec in Adults With Moderately Severe or Severe Hemophilia B: Results From the Phase 3 BENEGENE-2 Gene Therapy Trial

  Research and Practice in Thrombosis and Haemostasis · 2025-11-01

  articleOpen access1st authorCorresponding

  Background: Adeno-associated virus (AAV)-based gene therapy may stimulate a cellular immune response against capsid-presenting hepatocytes, which may cause a rise in transaminases and/or decrease in circulating factor IX (FIX:C). Corticosteroid administration generally controls the immune response. BENEGENE-2 is a pivotal phase 3 trial of fidanacogene elaparvovec, an AAV-based hemophilia B gene therapy.

  PublisherDOI

• Splenectomy for immune thrombotic thrombocytopenic purpura: a systematic review and meta-analysis

  Journal of Thrombosis and Haemostasis · 2025-07-18

  reviewSenior author
  PublisherDOI

• Incorporating Preprints in Systematic Reviews: A Preliminary Study of a Novel Method for Rapid Evidence Synthesis

  medRxiv · 2025-07-16

  preprintOpen accessCorresponding

  Objectives: By October 1, 2024, over 450,000 COVID-19 manuscripts were published, with 10% posted as unreviewed preprints. While they accelerate knowledge sharing, their inconsistent quality complicates systematic studies. Materials and Methods: We propose a two-stage method to include preprints in meta-analyses. In Stage A, preprints are integrated through restriction or imputation and weighted by a confidence score reflecting their publication likelihood. In Stage B, we assess and adjust for potential publication or reporting biases. Results: This preliminary study employed a two-stage procedure validated with two COVID-19 treatment case studies. For hydroxychloroquine, the relative risk (RR) was 1.06 [95% CI: 0.62, 1.80], suggesting no mortality benefit over placebo. For corticosteroids, the RR was 0.88 [95% CI: 0.62, 1.27], which, while not statistically significant, aligns with evidence supporting a mortality benefit. Discussion: Our research aims to bridge a significant methodological gap by providing a solution for timely evidence synthesis, particularly in the face of the overwhelming number of publications surrounding COVID-19. Conclusion: This preliminary study presents a method to efficiently synthesize COVID-19 research, including non-peer-reviewed preprints, to support clinical and policy decisions amidst the information surge.

  PublisherOA PDFDOI

• HTRS2025.P2.78 REAL-WORLD UTILIZATION of EPTACOG BETA* in the USA

  Research and Practice in Thrombosis and Haemostasis · 2025-11-01

  articleOpen accessSenior author

  Background: Eptacog beta is approved in the USA for the treatment of bleeding events (BEs) in adults and adolescents with hemophilia A or B with inhibitors (HABI). However, few data have been published on its real-world utilization in the USA.

  PublisherDOI

• Ianalumab retreatment in adults with primary immune thrombocytopenia (ITP) or warm-antibody autoimmune hemolytic anemia (wAIHA) who benefitted from previous ianalumab treatment: A phase 2 exploratory study

  Blood · 2025-11-03

  article

  Abstract Background: Immune thrombocytopenia (ITP) is a rare, acquired, immune-mediated disease characterized by a decrease in platelet count, leading to an increased risk of bleeding. The goal of ITP therapy is to maintain safe platelet counts to minimize bleeding while limiting treatment-related risks. Corticosteroids (CS) are recommended as first-line treatment in ITP, while second-line recommendations include thrombopoietin receptor agonists (TPO-RAs), rituximab, or splenectomy (Neunert et al. Blood Adv. 2019). Warm autoimmune hemolytic anemia (wAIHA) is also a rare immune-mediated condition characterized by erythrocyte destruction by self-reactive IgG, resulting in anemia of varying severity. The cornerstone of first-line treatment is CS, with rituximab becoming the preferred second-line therapy for wAIHA (Yui JC, Brodsky RA. Hematol Oncol Clin North Am. 2022). In both ITP and wAIHA, treatment options are limited when patients experience relapse or treatment resistance, necessitating cycling through limited therapeutic classes with diminishing efficacy. Ianalumab is a fully human monoclonal antibody that binds B-cell-activating factor receptor (BAFF-R) with a novel dual mechanism of action of BAFF/BAFF-R blockade and enhanced antibody-dependent cellular cytotoxicity-mediated B-cell depletion. Primary analysis of Week (Wk) 25 data of the VAYHIT3 phase 2 trial in heavily pretreated patients with primary ITP found nearly half of the patients achieving a confirmed response with adverse events consistent with ianalumab's safety profile from trials in other indications. To establish ianalumab as a treatment capable of inducing durable responses, two phase 3 trials in adult patients with ITP (VAYHIT1 in first-line and VAYHIT2 in second-line) and one phase 3 trial in patients with wAIHA (VAYHIA) are ongoing. Aims: This study (VAY RE-HIT, NCT07039422) aims to assess the efficacy and safety of a second course of ianalumab in patients with primary ITP or primary/secondary wAIHA who benefitted from their first treatment course. Methods: In this multicenter, phase 2 exploratory study, adult patients with primary ITP or primary/secondary wAIHA, who benefited from the first course of ianalumab in the parent pivotal trials but later experienced treatment failure (≥2 years after the last infusion ianalumab/placebo in VAYHIT1 and 2 trials) or lost durable response (≥2 years in blinded cohorts or Wk 20 in the cross-over arm in VAYHIA trial) and subsequently needed further therapy, will be included. Rescue medication and/or bridging therapy with CS (ITP, wAIHA) or TPO-RAs (ITP) are allowed at the defined timepoints. Patients with Evans syndrome or other cytopenias (except anemia due to blood loss or iron deficiency), secondary wAIHA with bone marrow involvement of the primary lymphoid malignancy, neutrophils <1000/mm3 or IgG <5 g/L at screening will be excluded. Once the parent trials are unblinded, patients who received placebo will not be eligible. Ianalumab will be administered intravenously with the same dose (lower dose or higher dose) used in the parent trials (a total of 4 doses) until the data readout; thereafter, the recommended dose will be administered for all newly recruited patients. The study consists of a screening period (up to 14 days before the first dose), treatment period (until Wk 17 Day 1 visit), and follow-up (FU) period up to 2 years after the last dose (efficacy and safety FU; safety FU only for treatment failure or if loss of durable response occurs). The primary endpoints are (i) treatment failure by 12 months (any of the following - platelet count <30 G/L, use of bridging or rescue therapy after 8 wks, new ITP treatment, death or inability to taper TPO-RA by Wk 24 when treated as bridging therapy) after the start of the second course of ianalumab for patients with ITP and (ii) durable response (Hb ≥10 g/dL and ≥2 g/dL increase from baseline) for at least 8 consecutive wks (during Wks 9-25) without rescue treatment for patients with wAIHA. Patients who were randomized to placebo in the corresponding parent study will not be included in the population of the primary estimand. The secondary endpoints for both patients with ITP and wAIHA include response and complete response rates and the number and proportion of patients receiving rescue treatment and/or new ITP/wAIHA therapy. Additionally, safety, pharmacokinetics, and immunogenicity assessments will be conducted. Results: None.Conclusion: Enrollment is ongoing.

  PublisherDOI

• Immune Thrombotic Thrombocytopenic Purpura

  JAMA · 2025-05-19 · 17 citations

  articleSenior author

  Importance: Immune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy that presents with microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. Worldwide annual incidence of iTTP is 2 cases per million to 6 cases per million. Observations: Immune TTP is caused by an autoantibody to a disintegrin and metallopeptidase with thrombospondin type 1 motif 13 (ADAMTS13), an enzyme that cleaves von Willebrand factor (vWF). With severely low ADAMTS13 activity (<10%), large multimers of vWF accumulate and bind platelets, forming microvasculature thromboses that cause ischemic organ injury (eg, myocardial infarction and stroke). The incidence of iTTP is higher in adults than children (incident rate ratio [IRR], 31.62 per million person-years [95% CI, 14.68-68.10]), females than males (IRR, 3.19 [95% CI, 2.65-3.85]), and Black compared with non-Black individuals (IRR, 7.09 [95% CI, 6.05-8.31]). Common presenting symptoms are neurologic (eg, headache, confusion, or seizures [39%-80%]) and abdominal pain (35%-39%). For patients presenting with MAHA and thrombocytopenia, clinical prediction scores for iTTP using laboratory data, such as platelet count less than 30 × 109/L and creatinine level less than 2.0 mg/dL (176.8 μmol/L), can help guide empirical treatment initiation for iTTP before ADAMTS13 results are available. Prompt initiation of therapy with therapeutic plasma exchange, corticosteroids, and rituximab improves survival with iTTP from almost zero to approximately 93%. Caplacizumab, a synthetic small antibody (nanobody) that blocks platelet binding to vWF, administered concurrently with immunosuppression and therapeutic plasma exchange and continued until ADAMTS13 recovery, reduces the time to normalization of platelet count and decreases the risk of early recurrence (defined as within 30 days of completing therapeutic plasma exchange) compared with placebo (risk difference [RD], -29% [95% CI, -42 to -14%]) but increases bleeding risk (RD, 17% [95% CI, 4%-30%]). After obtaining clinical remission (defined as at least 30 days of sustained normalization of platelet count, decreased serum lactate dehydrogenase level, and absence of new or progressive ischemic organ injury without therapeutic plasma exchange or caplacizumab), 16% of patients have at least 1 relapse of iTTP. Regular monitoring of ADAMTS13 activity in remission and administration of rituximab when ADAMTS13 activity is less than 20% reduces risk of relapse (odds ratio, 0.09 [95% CI, 0.04-0.24]). Conclusions and Relevance: Immune TTP is a rare immune-mediated disorder that presents with thrombocytopenia and MAHA and may cause life-threatening thrombosis. Treatment with therapeutic plasma exchange, corticosteroids, and rituximab is associated with 30-day survival rates of more than 90%. Addition of caplacizumab shortens time to normalization of platelet count and reduces recurrences while receiving the drug but increases bleeding risk. Monitoring ADAMTS13 activity in survivors and initiation of rituximab for those with low ADAMTS13 activity reduces the risk of clinical relapse.

  PublisherDOI

• Primary results from VAYHIT2, a randomized, double-blind, phase 3 trial of ianalumab plus eltrombopag versus placebo plus eltrombopag in patients with primary immune thrombocytopenia (ITP) who failed first-line corticosteroid treatment

  Blood · 2025-11-24 · 2 citations

  articleOpen access

  Abstract Introduction: B cells and the B-cell activating factor (BAFF) pathway are key in immune thrombocytopenia (ITP) pathophysiology. Ianalumab is a novel, first-in-class monoclonal antibody which binds to and blocks BAFF receptor, causing enhanced depletion of B cells via antibody-dependent cellular cytotoxicity and inhibition of B-cell activation, maturation, proliferation, and survival. We hypothesize that early intervention with ianalumab may provide a disease-modifying effect, such that the typical natural history of ITP is ameliorated in a significant proportion of patients (pts). Methods: VAYHIT2 (NCT05653219) is a randomized, double-blind, placebo-controlled, Phase 3 study of ianalumab in adults with primary ITP. Pts had insufficient response to/relapse after first-line corticosteroid therapy (± intravenous [IV] immunoglobulin), platelet (PLT) count &amp;lt;30×109/L, and were naive to and had indication for second-line ITP treatment. Pts were randomized (1:1:1) to receive eltrombopag plus either ianalumab 9mg/kg or 3mg/kg or placebo. Ianalumab or placebo was administered as four once-monthly IV infusions, simultaneously with daily eltrombopag for 16 weeks then an 8-week eltrombopag tapering period. The primary endpoint was time to treatment failure (TTF), defined as time from randomization until PLT count &amp;lt;30×109/L or start of rescue therapy 8 weeks after randomization, start of a new ITP therapy at any time, inability to taper or discontinue eltrombopag by week 24, or death. The key secondary endpoint was stable response at 6 months (SR6), defined as having ≥75% of PLT counts between weeks 19 and 25 being ≥50x109/L without rescue or new ITP treatment. On-treatment safety outcomes were assessed from first study drug infusion to 28 days following the last infusion; adverse events (AEs) associated with B-cell depletion were assessed until end of study. Results: Of 152 pts enrolled, 50 were randomized to ianalumab 9mg/kg, 51 to ianalumab 3mg/kg, and 51 to placebo. Pt characteristics were generally balanced between arms. Median (interquartile range) follow-up: 12.9 (8.6–18.0), 13.6 (8.4–18.1), and 11.6 (8.1–18.2) months in the ianalumab 9mg/kg, 3mg/kg, and placebo arms, respectively. TTF was significantly longer with ianalumab 9mg/kg (HR 0.55, 95% CI 0.32–0.92; log-rank p=0.021) and ianalumab 3mg/kg (HR 0.58, 95% CI 0.34–0.98; log-rank p=0.023), vs placebo; median (95% CI) TTF was 13.0 (5.1–not estimable [NE]), NE (3.7–NE), and 4.7 (3.9–5.6) months, respectively. Significantly more pts achieved SR6 with ianalumab 9mg/kg (31 [62.0%]) vs placebo (20 [39.2%]), Cochran-Mantel-Haentzel (CMH) p=0.023; and ianalumab 3mg/kg (29 [56.9%], not reaching statistical significance compared with placebo, CMH p=0.035). At 6 months, response (PLT≥50x109/L) and complete response (PLT≥100×109/L) rates were 73.5% and 55.1%, respectively with ianalumab 9mg/kg and 48.0% and 26.0%, respectively with placebo. At the end of the eltrombopag tapering period, PROMIS short-form v1.0 fatigue 13a showed reduction of fatigue (mean [SD] change in T-score from baseline) of -7.7 [8.9], and -3.6 [7.0] with ianalumab 9 mg/kg and placebo, respectively. All-grade AE rates were similar between arms (84.0%–94.0%). Grade ≥3 AEs occurred in 12 (24.0%), 10 (20.0%), and 2 (3.9%) pts in the ianalumab 9mg/kg, ianalumab 3mg/kg and placebo arms, respectively. All SAEs as assessed by investigator were unrelated to study drug except for 1 event (Grade 1 palpitations) in the ianalumab 3mg/kg arm. Frequency and severity of infections (including Grade ≥3) were similar across arms. In the ianalumab 9mg/kg, ianalumab 3mg/kg, and placebo arms, respectively: infusion-related reactions (14.0%, 8.0%, and 7.8%, all Grade 1/2), neutropenia (14.0%,10.0%, and 2.0%) and allergic hypersensitivity reactions (0%, 0% and 2.0%) occurred. Grade ≥3 neutropenia occurred in 5 (10.0%) and 2 (4.0%) pts in the ianalumab 9mg/kg and 3mg/kg arms, respectively. There were no on-treatment AEs leading to ianalumab discontinuations; 1 reported in post-treatment period (started &amp;gt;28 days post-treatment). Conclusions : Ianalumab in combination with eltrombopag prolonged TTF, improved SR6, reduced fatigue, facilitated tapering off eltrombopag, and delayed need for subsequent therapy in pts with primary ITP previously treated with corticosteroids. Ianalumab was well tolerated, with no observed increase in infection risk relative to placebo. Ianalumab may be disease-modifying when used early in the course of ITP.

  PublisherOA PDFDOI

Recent grants

• Improving the diagnosis of heparin-induced thrombocytopenia

  NIH · $436k · 2012–2015

Frequent coauthors

• Holger J. Schünemann

  Cochrane

  57 shared

• Robby Nieuwlaat

  McMaster University

  49 shared

• Wojtek Wiercioch

  McMaster University

  44 shared

• Reem A. Mustafa

  University of Kansas Medical Center

  40 shared

• Douglas B. Cines

  University of Pennsylvania

  35 shared

• Stephen J. Kovach

  University of Pennsylvania

  34 shared

• Deborah Siegal

  Ottawa Hospital

  31 shared

• Thita Chiasakul

  Chulalongkorn University

  30 shared

Education

• B.S., Biological Sciences

  Cornell University

  1998

• M.D., Medicine

  Yale University

  2003

• M.S., Translational Research

  University of Pennsylvania

  2010