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Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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Updated: Oct 16, 2025

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Refractory DLBCL: Challenges and Treatment.

Mendel Goldfinger1, Dennis L Cooper2

  • 1Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York.

Clinical Lymphoma, Myeloma & Leukemia
|October 20, 2021
PubMed
Summary
This summary is machine-generated.

Front-line diffuse large B cell lymphoma (DLBCL) treatment remains R/CHOP, but novel therapies like CAR-T cells offer hope for recurrent DLBCL. Circulating tumor DNA may aid early relapse detection.

Keywords:
Antibody-drug conjugatesBispecific T-cell engagersCAR-T cellsDLBCL

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Area of Science:

  • Hematology
  • Oncology
  • Immunotherapy

Background:

  • Diffuse large B cell lymphoma (DLBCL) treatment has seen limited evolution from R/CHOP, despite advances in understanding its pathology.
  • Genetic insights into DLBCL cell of origin have not yet translated into significantly altered treatment paradigms.
  • Early treatment response assessment using PET-CT, effective in Hodgkin lymphoma, is still under development for DLBCL.

Purpose of the Study:

  • To review novel therapeutic agents for relapsed or refractory DLBCL.
  • To explore the potential sequencing and earlier application of these new therapies.
  • To discuss emerging biomarkers for early detection of treatment failure.

Main Methods:

  • Review of current literature on DLBCL treatment.
  • Analysis of novel therapeutic agents including CAR-T cells, bispecific T-cell engagers (BiTEs), antibody-drug conjugates, and monoclonal antibodies.
  • Discussion of circulating tumor DNA (ctDNA) and PET-CT for response assessment.

Main Results:

  • While front-line DLBCL therapy is stagnant, recurrent disease treatment is rapidly advancing.
  • Novel immunotherapies and targeted agents show promise for long-term disease control and potential cure in relapsed DLBCL.
  • Circulating tumor DNA (ctDNA) combined with PET-CT may enable earlier identification of treatment failure or relapse.

Conclusions:

  • Emerging therapies offer significant hope for patients with relapsed/refractory DLBCL, potentially leading to chemotherapy-free strategies.
  • The sequencing and earlier integration of these novel agents into treatment protocols warrant further investigation.
  • Advances in biomarkers like ctDNA could revolutionize early detection and management of DLBCL.