Early results from an ongoing Phase I clinical trial ( NCT03090659) in China has 33 out of 35 (94%) patients with relapsed or treatment-resistant (refractory) myeloma in clinical remission (complete or near complete) with only mild side effects. This is the result of a new type of immunotherapy, chimeric antigen receptor (CAR) T-cell, which targets a protein called B-cell maturation antigen (BCMA), a protein that plays a role in progression of the disease. The study was featured in an abstract presented on June 5 at the  2017 American Society of Clinical Oncology (ASCO) Annual Meeting.

T-cells are types of white blood cells that migrate to, and form in the thymus gland in the neck. They play essential roles in the functioning of the immune system by acting like soldiers who find and destroy targeted invaders (antigens) throughout the body. CAR T-cell therapy works by collecting T-cells from the blood of patients and genetically engineering them to produce special receptors (CARs) on their surface that recognize the specific protein (antigen) that is highly produced by their cancer cells. The engineered CAR T-cells are then grown in the laboratory and injected back into the patient to fight their cancer cells.

In the trial, patients received three split doses of engineered CAR T-cells over the period of one week and began to show signs of treatment efficacy as early as 10 days after the first injection. The objective response rate, a defined level of tumour shrinkage, occurred in all 35 patients (100%), and clinical remission was achieved within 2 months of receiving the therapy.

To date, 19 patients have been followed for more than four months. Of those patients, 14 (74%) achieved a stringent complete response (sCR), 4 (21%) achieved a very good partial response (VGPR) and 1 (5%) patient met the criteria for a partial response (PR). Overall, 5 (36%) patients who have been followed for longer than 1 year remain in sCR and free of minimal residual disease (MRD or no detectable cancer cells in the bone marrow). Only one patient’s disease relapsed from a VGPR with an extramedullary lesion reappearing after three months. None of the patients who achieved a sCR relapsed. 

The majority of the patients (14; 74%) experienced cytokine release syndrome (CRS), a potentially dangerous side effect of the therapy that includes fever, difficulty breathing, low blood pressure and problems with multiple organs. Only 2 cases were severe (grade 3), however they recovered upon receiving treatment to combat inflammation. Six (6) patients did not experience CRS. The rest of patients experienced only mild and manageable symptoms. No patients had grade 4 or 5 CRS and there were no treatment-related deaths. There were no signs of any neurologic side effects, another common complication from the therapy.

The researchers plan to enroll a total of 100 patients in this clinical trial and also plan to launch a similar study in the United States. Moreover, they would like to explore this treatment in newly diagnosed myeloma patients.

Early results from another ongoing Phase I BCMA CAR T-cell study ( NCT02658929) was also presented at the 2017 ASCO Annual Meeting. This study, conducted in the United States, is assessing BCMA CAR T-cell dose safety and effectiveness in order to find the effective dose for patients with heavily pre-treated (3 or more prior regimens) relapsed and/or refractory myeloma. Prior to receiving the cells, patients receive a conditioning regimen of cyclophosphamide and fludarabine. To date, four different BCMA CAR T-cell dose levels (50 x 106, 150 x 106, 450 x 106 and 800 x 106) have been tested in a total of 21 patients. The researchers anticipate enrollment of up to 50 patients and are also planning Phase II trial based on the Phase I results.

Safety is being evaluated in all 21 patients and 18 of those patients are being restaged to evaluate treatment efficacy. The 15 (83%) patients who received an adequate amount of cells (50 x 106) have not progressed with 11 (73%) patients achieving a VGPR or better and 4 (27%) patients with a CR. Four (27%) patients have reached full remission with no MRD, including some that are more than 1 year following treatment.

Overall, 15 (71%) patients experienced mild cases of CRS that were successfully treated with anti-inflammatory drugs and the study found no dose-limiting toxicities. These results are further enhanced by the fact that the heavily pre-treated patients enrolled in this trial have a median of seven prior therapies.

Dr Jesus G Berdeja, the lead author of the ASCO abstract cited above will be a guest speaker at the upcoming 2017 Myeloma Canada Scientific Roundtable being held in Montreal in September.