Until recently, multiple myeloma patients were reliant upon treatment with immunomodulatory drugs, anti-CD38 antibodies, proteasome inhibitors, and autologous (patient-derived) stem cell transplants. According to a recent article in CancerConnect, patients who fail these therapies may be eligible for a new treatment called CAR T-cell therapy.
A study recently published in the NEJM reports that CAR T-cell therapy has been responsible for deep and continued remissions in recurrent cases of multiple myeloma (MM). The Journal reported that approximately seventy-five percent of patients in the study had a significant response to the therapy. About one-third of this group had a complete response which means that all evidence of cancer had disappeared.
About CAR T-Cell Therapy
Chimeric antigen receptor T-cells (CAR-T) therapy has made rapid advances as a new type of immunotherapy to treat cancer. The therapy involves removing and engineering the patient’s T cells so they can identify and kill the patient’s MM cells.
Using a patient’s immune cells against cancer has the potential not only to treat lymphomas but has recently made advancements in treating MM.
How The Immune System Can Fight Back
By now we are all aware of cancer cells’ ability to avoid attacks from our immune system. Our immune cells naturally go on the offensive against threats from bacteria and viruses.
With respect to detecting cancer cells, CAR T-cell therapy is emerging as an effective method of treating MM and has been FDA approved for MM that is resistant to treatment (refractory).
About Serum B-cell maturation antigen (sBCMA)
B-cell maturation antigen (BCMA) is primarily expressed on malignant plasma cells of most MM patients. It can be said that BCMA is responsible for the growth and survival of malignant plasma cells.
sBCMA is currently the primary target of CAR T-cell therapy. It is being used as a marker to predict response to therapy and to gauge overall and progression-free MM.
About Abecma (idecabtagene vicleucel)
Abecma, a/k/a ide-cel, has the distinction of being the first BCMA CAR T-cell immunotherapy that is approved to treat MM patients who are treatment-resistant or have relapsed. Ide-cell uses typical CAR T-cell therapies and binds to the tumor cells thereby destroying the malignant cells (apoptosis).
Patients treated with Abecma were evaluated at thirteen months with seventy-three percent responding to treatment. Thirty-three percent experienced a complete response. The average time patients were free from progression after treatment was eight or nine months. Two years after treatment several patients are still in remission.
These numbers compare favorably against drugs currently in use such as Panobinostat, Selinexor, and isatuximab. The response rate for these drugs has been 25-30% with progression-free survival of three to four months.
The aforementioned results led to ide-cell’s approval by the FDA as standard treatment for relapsed or refractory MM patients.
The clinical trial that led to the FDA approval had enrolled 140 patients. Ide-cel was administered to 128 patients at target dose levels. In order to be eligible, patients had to have received one to three previous therapies and were refractory to the most recent treatment. The progression should have occurred within a sixty-day period after the last treatment.
In total, ninety-eight percent of patients were responsive to therapy including a complete response of eighty percent. Ninety percent of patients experienced minimal residual disease (MRD) negativity which means there is no visible evidence of cancer.
Sixty-six percent of patients survived eighteen months after treatment.
Adverse Events
At ninety-six percent, neutropenia (low neutrophils) was the most frequently reported side effect. Also, eighty-one percent of patients reported anemia, and seventy-nine percent reported thrombocytopenia (low platelets).
Ninety-five percent of the clinical trial patients reported cytokine release syndrome (CRS) that began seven days after infusion and lasted about four days. Most cases of CRS were resolved within fourteen days with the exception of one incident. Neurotoxicity occurred in twenty-one percent of patients.
Death from various complications occurred to six patients including CRS, sepsis, respiratory failure, lung abscess, and neurotoxicity.
About Allogene
The initial results for the ALLO-715 UNIVERSAL study in relapsed/refractory MM were reported at the December 2020 meeting of the American Hematology Society.
This study marks the first-in-human study of allogeneic (stem cells from a donor other than the patient) CAR T BCMA therapy (NCT04093596). Of thirty-one patients that participated, neurotoxicity and low-grade CRS were reported in forty-five percent of patients. The CRS was apparently manageable using standard therapies.
Enrollment in the UNIVERSAL trial at higher doses will continue in order to optimize this therapy. The complete article is available here.
