Myeloma landscape and future directions
The development in the last ten years of new myeloma treatments has greatly improved survival and quality of life for people with myeloma. There are emerging therapies like CAR-T cell therapy or bispecific antibodies with promising results
The development of anti-myeloma treatments over the last 10 years, has greatly improved the prospects and quality of life for people with myeloma. Combinations of these treatments authorised for use in Europe and the indications are shown below:
- belantamab mafodotin (Blenrep) is approved alone (as a monotherapy) for the treatment of patients that have had at least four prior lines of therapies (including a proteosome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody) and their myeloma continues to worsen.
- bortezomib (Velcade) is approved alone or in combination with doxorubicin (a chemotherapy drug) or dexamethasone (a steroid) for patients that have received at least one prior therapy and are not eligible (or have previously had) a stem cell transplant.
- carfilzomib (Kyprolis) is approved in combination with dexamethasone with or without lenalidomide (Revlimid) for patients that have had at least one prior therapy.
- daratumumab (Darzalex) is approved in combination with lenalidomide and dexamethasone, or with bortezomib (Velcade), melphalan (a chemotherapy drug) and prednisone (a steroid) for the treatment of newly-diagnosed patients who are ineligible for stem cell transplant; it is also approved in combination with bortezomib (Velcade), thalidomide, and dexamethasone for the treatment of newly-diagnosed patients that are eligible for transplant; is also approved in combination with lenalidomide and dexamethasone or bortezomib (Velcade) and dexamethasone for treatment of patients that have had at least one prior therapy; or it is approved alone (as a monotherapy) for relapsed refractory patients that have previously had a proteosome inhibitor, immunomodulatory agent and still have worsening disease.
- elotuzumab (Empliciti) is approved in combination with lenalidomide (Revlimid) and dexamethasone in patients that have received 1-3 prior therapies. It is also approved in combination with pomalidomide (Imnovid) and dexamethasone for patients that have had at least 2 prior therapies, including lenalidomide (Revlimid), and a proteosome inhibitor and their disease has worsened on their last treatment.
- idecabtagene vicleucel (Abecma): is a chimeric antigen receptor (CAR-T) cell therapy and is approved alone for patients that have relapsed or refractory disease and have previously been treated with at least three therapies an immunomodulatory agent, a proteasome inhibitor and an anti‑CD38 antibody.
- isatuximab (Sarclisa) is approved in combination with pomalidomide (Imnovid) and dexamethasone for patients that have had at least two prior therapies (inclusive of lenalidomide (Revlimid) and a proteosome inhibitor) and their disease has worsened on their last treatment.
- ixazomib (Ninlaro) is approved in combination with lenalidomide (Revlimid) and dexamethasone for patients that have had at least one prior therapy.
- lenalidomide (Revlimid) is approved alone for maintenance treatment of patients with newly diagnosed myeloma that have just undergone stem cell transplant; also in combination with dexamethasone with or without bortezomib (Velcade), or melphalan and prednisone for newly-diagnosed patients who are ineligible for stem cell transplant; also in combination with dexamethasone for patients who have had at least one prior therapy
- thalidomide is approved in combination with melphalan and prednisone for newly-diagnosed patients that are older than 65 and ineligible for stem cell transplant.
- panobinostat (Farydak) is approved in combination with bortezomib (Velcade) and dexamethasone, for patients that have had at least two prior therapies, including bortezomib and an immunomodulatory agent.
- pomalidomide (Imnovid) is approved in combination with bortezomib (Velcade) and dexamethasone for patients that have received at least one prior treatment regimen (inclusive of lenalidomide); it is also approved in combination with dexamethasone for patients who have had at least two prior treatment regiments (inclusive of lenalidomide [Revlimid] and bortezomib [Velcade]) and their disease continues to worsen.
- selinexor (Nexpovio): is used in combination with dexamethasone to treat patients that have had at least four previous treatments and their myeloma is no longer responding.
New targets and investigative drugs to treat myeloma
There continues to be significant research in the genetic changes causing myeloma and their influence on response to treatment.
Individual patients vary significantly, and even one person can respond differently to a medication if it is given at different stages in their myeloma. This might be one reason why patients sometimes fail to respond well to a drug which was helpful earlier in their illness, or vice versa., Recent advances in genetic analytical techniques are now enabling these genetic alterations to be detected. The gene sequence responsible for myeloma has been completely mapped by the Multiple Myeloma Genomics Initiative of the Multiple Myeloma Research Foundation. The concept of personalised medicine using genetic analysis will likely leading to a clearer understanding of how treatments can be tailored to individual patients. Further studies of these differences will eventually enable treatments to be adjusted and developed to suit individual patients, based on their gene sequences, fitness, and specific disease characteristics.
As myeloma is relatively rare, patients unfortunately do not always have access to the same standard of care available wherever they live. For example, university hospitals in major cities have myeloma specialists who may be engaged in current drug trials and are fully aware of the latest findings on the uses and advantages of innovative treatments. Patients of rural, local hospitals are often in the care of general haematologists or oncologists who may not be fully informed on the latest research developments, clinical trials and complexities of myeloma. In some countries, patients have little chance to participate in the clinical trials of new treatments that could offer them improved treatment or reduced side-effects. Continuing research into myeloma is urgently needed, as it is important that recent myeloma research findings in these centres are quickly translated into treatments that are available to more myeloma patients.
There are many therapies currently under investigation for the treatment of myeloma, many with promising results. While the above treatments have significantly improved survival, myeloma still remains an incurable illness. In patients who have exhausted all their previous treatment options they may be eligible to enrol in a clinical trial.
Some types of drugs under investigation for the treatment of myeloma are chimeric antigen receptor cell therapy (also known as CAR-T-cell therapy) and bispecific monoclonal antibodies. Both these treatments harness the immune system to fight myeloma.
CAR T-cell therapy
CAR T-cell therapy first removes, then genetically programmes, your body’s T-cells (a type of immune cell). After the genetically programmed T-cells are reinfused into your body they can find and kill myeloma cells. This type of treatment has been shown to be very effective in myeloma, but this remains under investigation as response may not be long lasting.
MPE has developed several educational resources on CAR-T to help you understand how it works, and answer frequently asked questions. Click here to explore all the other CAR-T resources available on our webiste. Check here educational resources on myeloma.
Bispecific monoclonal antibodies are laboratory produced antibodies that bind to both myeloma cells and an immune cell to stimulate immune cells to kill myeloma cells. The preliminary results from these studies have also shown that they are effective.
While these emerging therapies are promising, they are not without significant and sometimes dangerous side effects. Therefore, before considering enrolment in a clinical trial you should make sure you are well informed. Next, we will talk about the details on what is involved and define the components of a clinical trial.
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