Non-Hodgkin’s Lymphoma: Drug Therapy

Therapeutic target

  • Remission

Therapy recommendations

  • Therapy should always be provided in centers.
  • Therapy of first choice is chemotherapy
  • If necessary, adjuvant (“complementary”) radiotherapy of the skull.
  • If infestation of the CNS (central nervous system) is suspected, intrathecal (“into the cerebrospinal fluid space”, nerve fluid) chemotherapy is given
  • If it comes to a relapse (recurrence of the disease) so may be a high-dose chemotherapy is useful, which must be followed by a stem cell transplant.
  • Like the group of non-Hodgkin’s lymphomas (NHL), the therapy protocols are very diverse (see classification below) and are not presented here.
  • Follicular lymphoma (B-cell non-Hodgkin lymphoma (B-NHL); most common type of NHL; approximately 20-35% of all NHLs):
    • Antibody obinutuzumab (CD20 antibody) in combination with chemotherapy (e.g., CHOP (cyclophosphamide, vincristine, prednisone, adriamycin)).
    • Rituximab (monoclonal antibody (IgG-1-kappa immunoglobulin) against the surface antigen CD20) has increased the chances of cure for patients with non-Hodgkin lymphoma. (Median progression-free survival is now 6 to 10 years; overall survival rate at 3 years is 90%).
    • In a trial of rituximab–lenalidomide treatment (18 cycles of both drugs) followed by 12 cycles of rituximab monotherapy when patients had responded to initial therapy, 48% of patients achieved complete remission at 120 weeks (95% confidence interval 44 to 53%); progression-free survival at 3 years was 77% (72-80%).
  • Diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma (PMBCL): axicabtagene ciloleucel (CAR-T cell therapy* ):
    • Median follow-up of 15.1 months: 72% of patients (n = 73/101) who received a single infusion of axicabtagene ciloleucel responded to therapy, and 51% (n = 52/101) had a complete response; one year after infusion, 60% of patients were alive.
  • Cutaneous B-cell lymphoma
    • Mantle cell lymphoma
      • Ibrutinib (drug in the tyrosine kinase inhibitor class); may improve both PFS (progression-free survival) and OS (overall survival) compared with usual regimens; reduce OS by 29
      • CAR-T therapy KTE-X19 in mantle cell lymphoma.
  • Cutaneous T-cell lymphomas (CTCL; e.g., mycosis fungoides [see below of the disease “Mycosis fungoides] and Sézary syndrome):
    • Mogamulizumab (monoclonal antibody to C-C chemokine receptor 4 (CCR4): significantly increased progression-free survival (PFS), response, and quality of life in the phase III MAVORIC trial compared with the previous standard of care, vorinostat.The drug is approved for the treatment of adults with mycosis fungoides or Sézary syndrome who have received at least one prior systemic treatment.
    • Brentuximab vedotin (INN, trade name Adcetris): antibody-drug conjugate (ADC) directed against human CD30 antigen covalently bound to three to five molecules of the cytostatic monomethylauristatin E. In the ALCANZA trial, 56.3% of patients achieved ORR4 (objective response rate for at least 4 months) with brentuximab vedotin, compared with 12.5% in the control group; prolonged progression-free survival (PFS) with brentuximab vedotin by 13.2 months (16.7 vs. 3.5 months)
  • Indolent non-Hodgkin lymphomas (e.g., cutaneous T-cell lymphomas (mycosis fungoides and Sézary lymphoma), follicular lymphomas, immunocytoma, chronic lymphocytic leukemia (CLL)):
    • Step 1: In situ vaccination (T cells in the tumor should be made aware of the cancer cells in this process; this task is performed by the dendritic cells (DC); the dendrites take up the antigens with their long arms and present them to the T cells, which are thereby made aware of their target).
    • Step 2: Local radiation therapy: radiation causes destruction of individual tumor cells, leading to exposure of neoantigen. These are in turn taken up by the dendritic cells and again presented to the T cells as a target.

    In a small study of 11 patients who were at an advanced stage, tumor shrinkage occurred in 9 of the 11 patients under the above in situ vaccination; among them were two full remissions.

  • See also under “Further Therapy.”

* CAR-T cell therapy

CAR-T cell therapy (“chimeric antigen receptor T cells”): patient’s own T cells are genetically engineered outside the body (ex vivo) with chimeric antigen receptors (“CAR”) to specifically target the cancer. These cells are then reinfused into the body. They then bind to the corresponding tumor features (here: CD19) on the lymphoma cells and lead to a sustained immune response through the release of chemokines, cytokines and lytic molecules.Side effects: The release of the previously mentioned endogenous messenger substances (cytokine storm) can lead to high fever and life-threatening organ damage.Other possible side effects include tumor lysis syndrome (TLS; life-threatening metabolic derailment that can occur when a large number of tumor cells are suddenly destroyed) and neurotoxicity (property of a substance to have a damaging effect on nerve tissue). Note: No treatment recommendations are given here for the various primary cutaneous lymphomas because of their diversity and the constant changes in treatment regimens….