Multiple Myeloma: New Therapeutic Approaches

February 17, 2021

The daratumumab antibody was approved for the first time last year as an immunotherapy for the first-line treatment of multiple myeloma. Further immunotherapies are in the pipeline.

Maligne Plasmazellerkrankung

Multiple myeloma is a rare plasma cell disease that mostly affects the elderly. The disease occurs primarily in the bone marrow. There, the myeloma cells suppress normal blood formation and destroy the bone structure. Clinically, multiple myeloma is often noticeable in those affected by severe infections, poor exercise capacity, kidney dysfunction, bone pain and pathological fractures.

Great advances in therapy

Despite great advances in treatment, a permanent cure is usually not possible. In the field of immunotherapies in particular, however, there are diverse approaches to further improve the treatment and prognosis of patients with multiple myeloma.

Monoclonal antibodies now in the first line

With daratumumab (Darzalex®), a monoclonal antibody was approved for the first time in 2020 for the treatment of patients with newly diagnosed multiple myeloma. The antibody is directed against CD38, a glycoprotein that is expressed in large quantities on the cell surface of myeloma cells. Treatment with daratumumab leads to more and deeper remissions and prolongs progression-free survival without impairing subsequent stem cell mobilization. Therefore daratumumab in combination with bortezomib, thalidomide and dexamethasone can also be used in patients who are planned to have an autologous stem cell transplant. The anti-CD38 antibody isatuximab and the anti-SLAMF7 antibody elotuzumab are also currently being tested in first-line therapy. So far, both have only been approved for previously treated patients.

Immune-drug conjugates

Last year, an antibody-drug conjugate was approved for the first time for monotherapy in patients with advanced and often refractory multiple myeloma: Belantamab-Mafodotin (Blenrep®). The conjugate consists of a monoclonal antibody against the B-cell maturation antigen (BCMA) on myeloma cells and the mitosis inhibitor monomethyl auristatin F. After binding and absorption, the active ingredient is released inside the myeloma cells and leads to cell death.

Approval of CAR-T cells expected

High hopes are associated with CAR-T cell therapies, which in studies have achieved a very good response and, in some cases, longer-lasting remissions even in patients who have been previously treated. Important side effects are a cytokine release syndrome, neurological side effects, and infections caused by prolonged neutropenia. Approval of the first anti-BCMA CAR-T cell therapies for the treatment of patients with advanced multiple myeloma is expected in 2021.

Bispecific antibodies

The first study results with bispecific T-cell-recruiting antibodies, so-called BiTE (bispecific T-cell engagers), are also promising. These consist of two linked antibody fragments, one of which targets a typical surface protein of myeloma cells (e.g. BCMA), the second targets a surface antigen of T cells. In this way, cytotoxic T cells are coupled directly to the tumor cells and can trigger a targeted immune response.

conclusion for practice

  • The prognosis of patients with multiple myeloma has improved significantly in recent years.
  • Numerous new and promising therapies are currently being developed, especially in the field of immunotherapies.
  • Some new substances have already been approved – both for initial therapy and for advanced therapy lines.
  • In the case of pretreated patients in particular, it should be checked whether participation in clinical studies is possible.

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