ASH 2019: High response rate seen with BCMA-directed CAR T-cell therapy for multiple myeloma

7 Dec 2019
ASH 2019: High response rate seen with BCMA-directed CAR T-cell therapy for multiple myeloma

Patients with multiple myeloma who had received a median of five prior therapies, and for whom standard-of-care treatments were no longer working, had a high response rate when treated with the investigational CAR T-cell therapy JNJ-4528, which targets BCMA, a protein commonly found on the surface of multiple myeloma cancer cells.

“We are seeing a high response rate, with most patients achieving MRD negativity,” said lead study author Deepu Madduri, MD, of The Tisch Cancer Institute at Mount Sinai in New York. “Considering these patients have all received multiple prior therapies, these results are extremely encouraging.”

All evaluable patients receiving this CAR T-cell therapy have achieved MRD-negative disease state and 27 of 29 patients are progression free at a median follow-up of six months, Dr. Madduri said.

Multiple myeloma is a cancer of plasma cells, which are found in the bone marrow and are part of the immune system, the body’s defense system against infection.

Typical signs and symptoms of multiple myeloma may be bone pain or fractures, high levels of calcium in the blood, kidney damage, and anaemia.

Multiple myeloma affects an estimated 160,000 people each year, occurs most often in people over 60, and is slightly more common in men than in women.

Although new therapies for multiple myeloma have recently become available that can extend patients’ life expectancy, a cure for the disease remains elusive, Dr. Madduri said.

“We can get the disease into remission, but most patients unfortunately relapse, and outcomes are very poor for patients who have relapsed multiple times,” she said.

Researchers said that JNJ-4528 is a novel CAR T-cell therapy featuring two molecules that bind to BCMA, a protein found on the surface of multiple myeloma cells.

“We are learning that every CAR T-cell therapy is different,” said Dr. Madduri. “JNJ-4528 has a unique CAR T cell composition in patients, preferentially enriched in CD8 T cells, which are believed to be one of the most important T cells in killing cancer cells.”

This phase Ib/II trial is continuing to enrol patients.

Dr. Madduri reported results for the first 29 patients enrolled.

Patients’ T cells were collected and sent to a laboratory where they were genetically engineered to express JNJ-4528.

Prior to re-infusing these CAR T cells, the patients received three days of chemotherapy to “make room” in their immune systems for the engineered T cells.

Following chemotherapy, each patient received a single infusion of the JNJ-4528 CAR T cells.

They had blood and bone marrow exams at a minimum at 28 days, six months, and one year after treatment to assess their response.

The primary aims of the trial are to assess the therapy’s safety and to confirm the dose to be tested in a larger, phase II trial.

The median follow-up time in the current analysis is six months.

Overall, 100% of patients had a clinical response to JNJ-4528.

Moreover, 66% had a stringent complete response, meaning that sensitive laboratory and microscopic tests found no evidence for myeloma proteins or cells in blood, urine, or bone marrow.

Most patients (93%) experienced CRS; one patient had severe (grade 3) CRS, and one patient died from its complications 99 days after the CAR T cell infusion. In 76% of patients, CRS was treated with tocilizumab.

“To see some patients in this heavily pretreated population surviving for a year or more with a one-time treatment and a manageable safety profile is remarkable,” Dr. Madduri said. “These patients feel that they have their quality of life back. They no longer have to come into the clinic for weekly treatments and some are well enough to travel.”

The phase II portion of this study is ongoing to evaluate the overall response rate of patients treated with JNJ-4528.

Additional clinical studies are evaluating the safety and efficacy of JNJ-4528 in different multiple myeloma treatment settings.

Source: American Society of Hematology

Watch the press conference here

Watch our interview with Prof Deepu Madduri here