Jordan Goldstein

All Publications

• Roadmap for developing MRD as an early endpoint for drug approval in lymphoma. Seminars in hematology Goldstein, J. S., Wang, S. X., Chamuleau, M. E., Alizadeh, A. A. 2026

  Abstract

  Advances in lymphoma therapy have extended survival, but exposed limitations of traditional trial endpoints efficacy assessments. We propose two MRD-informed endpoints to accelerate drug development and improve regulatory decision-making: modified PFS (mPFS) and undetectable MRD (uMRD) rate. mPFS is a specific variant of event free survival (EFS) defined as the time from study enrollment until positive end-of-treatment MRD, clinical progression, or death and has potential as a validated surrogate endpoint for traditional approval. uMRD rate at a prespecified timepoint measures depth of response and can be useful in early phase and later-line studies for accelerated approval. Here, we outline the potential that can be slow, reliant on inconsistent imaging studies, and insensitive to molecular disease burden. Novel surrogate trial endpoints can expand and accelerate innovative therapies reaching patients. Advances in technology have led to ultrasensitive methods for detection of measurable residual disease (MRD) in peripheral blood, including circulating tumor DNA (ctDNA) and immunoglobulin clonotype sequencing. MRD methods have been studied with clear biologic rationale and prognostic ability across lymphomas including large B-cell, mantle cell, Hodgkin, and follicular lymphoma. Incorporating MRD into trial endpoints can lead to shorter trial times and perhaps more accurate treatment endpoints incorporating MRD, detail the current MRD data in lymphomas, and provide a practical roadmap towards regulatory use of MRD-based surrogate endpoints to speed drug development.

  View details for DOI 10.1053/j.seminhematol.2026.03.007

  View details for PubMedID 41982010

• Non-invasive Mantle Cell Lymphoma risk stratification by inference of tumor proliferation from cfDNA Ashtari, A., Mutter, J., Tessoulin, B., Rossi, C., Boegeholz, J., Goldstein, J., Klanova, M., Kuehn, J., Alig, S., Schroers-Martin, J., Liu, C., Olsen, M., Kang, X., Trneny, M., Le Gouill, S., Diehn, M., Esfahani, M., Alizadeh, A. ELSEVIER. 2025: 1789-1790

  View details for DOI 10.1182/blood-2025-1789

  View details for Web of Science ID 001660185400040

• Spatial anatomical genomic heterogeneity and aberrant somatic hypermutation define clonal evolution pathways that predict treatment resistance in aggressive B-cell lymphomas Goldstein, J., Wang, S., Tessoulin, B., Liu, C., Scherer, F., Le Gouill, S., Chamuleau, M., Nijland, M., Diehn, M., Kurtz, D., Alizadeh, A. ELSEVIER. 2025: 354-355

  View details for DOI 10.1182/blood-2025-354

  View details for Web of Science ID 001659571100005

• Remission Assessment by Circulating Tumor DNA in Large B-cell Lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Roschewski, M., Kurtz, D. M., Westin, J. R., Lynch, R. C., Gopal, A. K., Alig, S. K., Sworder, B. J., Cherng, H. J., Kuffer, C., Blair, D., Brown, K., Goldstein, J. S., Schultz, A., Close, S., Chabon, J. J., Diehn, M., Wilson, W. H., Alizadeh, A. A. 2025: 101200JCO2501534

  Abstract

  Large B-cell lymphomas (LBCL) are curable, but patients with residual disease after therapy invariably experience progression. Ultrasensitive methods to detect circulating tumor DNA (ctDNA) as minimal measurable residual disease (MRD) may improve the determination of remission.We integrated data from five prospective studies of frontline anthracycline-based chemotherapy in patients with LBCL. Tumor-specific phased variants were identified from pretreatment samples and monitored at landmark timepoints. Serial plasma specimens were blindly analyzed for detectable ctDNA as MRD. MRD status was compared to conventional response criteria for prognosis of progression-free survival (PFS).We studied ctDNA-MRD in 137 patients by monitoring 409 plasma specimens over time. Detectable ctDNA rates decreased during therapy with 55% and 78% of patients achieving undetectable ctDNA after 2 cycles and at end of therapy, respectively. After a median follow-up of 37 months, the 2-year PFS for patients with detectable vs undetectable ctDNA after 2 cycles was 67% vs 96% (p=0.0025, hazard ratio 6.9) and after therapy was 29% vs 97% (p<0.0001, hazard ratio 28.7), respectively. Ninety-two (94%) patients with undetectable ctDNA at end of therapy remained alive without progression, while 19 (68%) patients with detectable ctDNA progressed or died. MRD status at end of therapy had greater prognostic utility than conventional lymphoma response criteria using PET scans (hazard ratio 3.6 for positive PET, and 28.3 for detectable ctDNA).Ultrasensitive circulating tumor DNA detection after frontline LBCL therapy is more prognostic than conventional radiographic response criteria. A refined definition of remission with ctDNA-MRD may improve clinical and psychological outcomes for patients with LBCL (Funded by the National Cancer Institute and others; ClinicalTrials.gov numbers, NCT04002947; NCT00398177; NCT02529852; NCT04231877; NCT04134936).

  View details for DOI 10.1200/JCO-25-01534

  View details for PubMedID 40802906

• Beyond Trial and Error: A Mathematical Model Wrangles DLBCL Heterogeneity Toward Optimizing Combination Therapy. Blood cancer discovery Goldstein, J. S., Phillips, N. A., Alizadeh, A. A. 2025: OF1-OF4

  Abstract

  In this issue of Blood Cancer Discovery, Pomeroy and Palmer present a new mathematical model, incorporating both inter- and intra-patient heterogeneity, to accurately predict outcomes for first-line combination therapies in diffuse large B-cell lymphoma. Their quantitative framework opens a range of possibilities for optimizing trial design and lymphoma therapy with potential to expedite clinical development. See related article by Pomeroy and Palmer, p. XX.

  View details for DOI 10.1158/2643-3230.BCD-25-0071

  View details for PubMedID 40232087

• Anatomic Genetic Heterogeneity Is Uncovered By Concurrent Cell-Free DNA and Tissue Profiling and Predicts Treatment Resistance in Diffuse Large B-Cell Lymphoma Goldstein, J. S., Scherer, F., Sworder, B. J., Diehn, M., Kurtz, D., Alizadeh, A. A. ELSEVIER. 2024: 4357-4358

  View details for DOI 10.1182/blood-2024-209735

  View details for Web of Science ID 001412802400042

• Baseline Prognostic Factors Do Not Predict End of Treatment Ctdna MRD Status and Have Limited Impact on MRD Prognostic Performance in DLBCL Goldstein, J. S., Roschewski, M., Kim, W., Yoon, S., Kim, S., Westin, J. R., Lynch, R. C., Alig, S. K., Close, S., Chabon, J., Rossi, D., Wilson, W. H., Kurtz, D., Alizadeh, A. A. ELSEVIER. 2024: 651-652

  View details for DOI 10.1182/blood-2024-211068

  View details for Web of Science ID 001415676400001

• Ultrasensitive Circulating Tumor DNA MRD Status Predicts Treatment Failure & Complements PET/CT throughout Treatment for Early and Advanced Stage Classic Hodgkin Lymphoma Boegeholz, J., Rossi, C., Goldstein, J. S., Alig, S. K., Garofalo, A., Esfahani, M., Schroers-Martin, J. G., Liu, C., Olsen, M., Kang, X., Tian, F., Kurtz, D., Andre, M., Fornecker, L., Casasnovas, O., Diehn, M., Ghesquieres, H., Alizadeh, A. A. ELSEVIER. 2024: 565-566

  View details for DOI 10.1182/blood-2024-201877

  View details for Web of Science ID 001414815800015

• The Clinical Impact and Cost-Effectiveness of PET-Based and Ctdna-Based Evaluation at End-of-Therapy after Frontline Treatment of DLBCL Kambhampati, S., Goldstein, J. S., Buller, S., Roschewski, M., Alizadeh, A. A., Thiruvengadam, N. ELSEVIER. 2024: 2276-2277

  View details for DOI 10.1182/blood-2024-203873

  View details for Web of Science ID 001412639100005

• Distinct Molecular Aberrations of Classic Hodgkin Lymphoma in Older Adults Identified By Comprehensive Genomic Profiling Rossi, C., Boegeholz, J., Goldstein, J. S., Shi, S., Su, S., Tessoulin, B., Alig, S. K., Garofalo, A., Esfahani, M., Schroers-Martin, J. G., Liu, C., Olsen, M., Kang, X., Tian, F., Kurtz, D., Sugio, T., Noordenbos, T., Andre, M., Fornecker, L., Julia, E., Traverse-Glehen, A., Casasnovas, O., Binkley, M. S., Diehn, M., Ghesquieres, H., Alizadeh, A. A. ELSEVIER. 2024: 853-854

  View details for DOI 10.1182/blood-2024-201644

  View details for Web of Science ID 001412608600046

• ViPOR's Venom - Rationally Targeting DLBCL with Precision. The New England journal of medicine Goldstein, J. S., Alizadeh, A. A. 2024; 390 (23): 2209-2211

  View details for DOI 10.1056/NEJMe2405437

  View details for PubMedID 38899699

• Ultrasensitive circulating tumor DNA (ctDNA) minimal residual disease (MRD) detection in early stage non-small cell lung cancer (NSCLC) Isbell, J. M., Goldstein, J., Hamilton, E. G., Liu, S., Eichholz, J., Buonocore, D. J., Rusch, V. W., Bott, M., Molena, D., Rocco, G., Yang, S., Rudin, C. M., Jones, D. R., Roff, A., Schultz, A., Chabon, J. J., Kurtz, D., Alizadeh, A. A., Li, B. T., Diehn, M. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557401867

• Optimizing Circulating Tumor DNA Limits of Detection for DLBCL during First Line Therapy Goldstein, J., Kim, W., Yoon, S., Kim, S., Roschewski, M., Westin, J., Lynch, R. C., Alig, S. K., Close, S., Chabon, J. J., Rossi, D., Wilson, W. H., Diehn, M., Alizadeh, A. A., Kurtz, D. M. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-187759

  View details for Web of Science ID 001159306700188

• Novel agents in relapsed/refractory diffuse large B-cell lymphoma. Hematological oncology Varma, G., Goldstein, J., Advani, R. H. 2023; 41 Suppl 1: 92-106

  Abstract

  Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), ineligible for or relapsing after autologous stem-cell transplant or chimeric antigen-receptor T-cell therapies have poor outcomes. Several novel agents, polatuzumab vedotin, tafasitamab, loncastuximab tesirine, and selinexor, have been approved and offer new opportunities for this difficult to treat population. Studies are evaluating combination of these agents with chemotherapy and other emerging therapies. Additionally, advances in our understanding of DLBCL biology, genetics, and immune microenvironment have allowed for the identification of new therapeutic targets like Ikaros and Aiolos, IRAK4, MALT1, and CD47 with several agents in ongoing clinical trials. In this chapter we review updated data supporting the use of the approved agents and discuss other emerging novel therapies for patients with R/R DLBCL.

  View details for DOI 10.1002/hon.3143

  View details for PubMedID 37294966