CAR-T Therapy for Multiple Myeloma Trial Marred by Patient Death

According to Biospace, Allogene’s trial of ALLO-715 for relapsed/refractory multiple myeloma was marred by a patient death. Data from this trial is slated to be presented in December at the 62nd Annual Meeting of the American Society of Hematology.

About Multiple Myeloma

Multiple myeloma is a form of cancer that impacts plasma cells. It causes them to accumulate in the bone marrow and push out healthy cells, resulting in M proteins. It is these proteins that cause the characteristic symptoms, which include bone pain, weight loss, nausea, loss of appetite, fatigue, kidney problems, constipation, frequent infections, mental fogginess, low blood count, excessive thirst, weakness or numbness in the legs, and hypercalcemia. While medical professionals do not know what causes this cancer, they do know that many myeloma cells are missing part or all of chromosome 13. Treatment options for multiple myeloma include chemotherapy, steroids, immunomodulatory drugs, HDAC inhibitors, and proteasome inhibitors.

About CAR-T Therapy

CAR-T therapy consists of taking blood, isolating the white blood cells, altering them so that they attack the patient’s cancer cells, and reinfusing them. There is autologous CAR-T therapy, which is the traditional form, where the blood is taken from the patient. There is also allogeneic, where the white blood cells did not come from the patient. This is the category that Allogene’s therapy falls into.

About the Study

Titled the UNIVERSAL trial, this phase 1 study showed promise, but it was marred by the death of a participant. 15 patients with advanced disease received escalating doses of ALLO-715 in combination with lower doses of ALLO-647.

Of the five patients who were given higher doses, three responded. Throughout all 15 patients, higher doses corresponded to more immune activity.

In terms of safety, there was no evidence of graft-vs-host disease or neurotoxicity; however, four patients experienced cytokine release syndrome. All cases were resolved, fortunately. Common grade 3 adverse effects include neutropenia, thrombocytopenia, anemia, and lymphopenia. Three grade 3 infections were also seen and treated as well.

The only grade 5 event was fungal pneumonia. Sadly, the patient passed away. After investigation, the death was attributed to the progression of disease and conditioning regimen.

Looking Forward

While there were positive aspects of the trial, the data is underwhelming when compared to that of autologous CAR-T therapies. But because the autologous form is so much more expensive, many companies have been looking into the allogeneic version. While they cost much less, data has yet to show if they are as effective.

There are two other therapies being developed for multiple myeloma as well. Bristol Myers Squibb is working with Bluebird Bio, and their CART-T therapy is currently being reviewed by the FDA. The second was developed by Legend Biotech and licensed by Johnson & Johnson, and it shows promise in the clinic.

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