Today’s ASCO meeting brought an interesting session on the use of antibodies In myeloma.
The first two talks were in the form of a debate regarding whether all myeloma patients should receive monoclonal antibodies at first relapse. First up was the MMRC’s Dr. Jacob Laubach from the Dana Farber Cancer Institute who took the “yes” position. Speaking about the two approved monoclonal antibodies in myeloma, Empliciti and Darzalex, Dr. Laubach noted
- They have unique mechanisms of action compared to other agents approved for first relapse
- They have established efficacy and are well tolerated
- They are broadly effective across many different myeloma subtypes
- They are ideal for sequencing with other treatments across subsequent lines of therapy
Taking the “no” position was Dr. Joe Mikhael of Mayo Clinic. Dr. Mikhael argued that
- myeloma is such a complicated disease that treatment approaches should not be linear and should take into account multiple mechansms of action in combination therapy
- other therapeutic approaches such as retreatment, or treatment with other and newer proteasome inhibitors (Kyprolis, Ninlaro), or immune modulators (Pomalyst) should also be considered at first relapse
- Optimization of other agents such as steroids, Farydak, doxorubicin should be considered
- Triplet therapies such as Pomalyst-Velcade-dex should be considered as well as doublets like Kyprolis-dex or Ninlaro-dex
- In addition, certain myeloma subtypes need specific treatment at relapse, for example
- Proteasome based therapy for t(4;14)
- Venetoclax for t(11;14)
- Proteasome inhibitor or Pomalyst for p53 del
- A second ASCT can sometimes be indicated
Finally, Dr. Mikhael noted that monoclonal antibodies may soon be approved as front line treatment (Darzalex has already been approved as front line for ASCT ineligible patients)
Dr. Faith Davies of UAMS finished the session with a presentation on future monoclonal antibodies and concentrated on BCMA targeting therapies, which bind directly to myeloma cells via the BCMA protein on their surface. She noted the
- Antibody drug conjugates such as GSK2857916 which carry a cell poison directly to myeloma cells, binding t BCMA on the surface and killing them
- Bi-specific antibodies which bind to both myeloma cells via BCMA and to T cells via a T cell receptor, bringing them into proximity so that the tumor cells can be destroyed by the T cell
- Checkpoint inhibitor antibodies which block the ability of myeloma cells to hide from the body’s immune system, allowing tumor cells to be recognized and eliminated
- CAR-T cells which are engineered to recognize BCMA on tumor cells and target them for destruction
- These therapies, currently in clinical trials, may soon win approval from the FDA and be added to the myeloma armamentarium.
Check back tomorrow for more ASCO highlights!