Treating Relapsed Multiple Myeloma With CAR T Cell Therapy Targeting GPRC5D

MSK patient Guillaume Arnould  high fives with his son.

With his disease currently in check, Guillaume Arnould is back to enjoying life with his family, including his son, Tristan.

Shortly after finding out his wife was pregnant with their son, Guillaume Arnould got terrible news about his own health: He had multiple myeloma, a rare blood cancer. He was just 33 years old. The following six years were a grueling succession of stem cell transplants, chemotherapy, and radiation. Yet the cancer was relentless.

“It was devastating for me and my family each time I relapsed,” says Guillaume. “You’re living with that sword of Damocles above your head all the time, and you don’t know when it’s going to fall.”

Coming to MSK for a Multiple Myeloma Stem Cell Transplant

Initially treated at another New York hospital, Guillaume says his doctor advised that his best hope would be Memorial Sloan Kettering Cancer Center (MSK). He had his second stem cell transplant under the care of hematologist-oncologist Sergio Giralt, MD, using cells from a donor — his younger brother, who flew over from France, where Guillaume grew up. The treatment was arduous, but it seemed to work — until it didn’t.

Three years ago, the disease was on the march again. Guillaume wondered if he had run out of options. Like most cancers, multiple myeloma becomes harder to treat every time it comes back. Guillaume despaired at the thought of saying goodbye to his wife, Ruth, and Tristan, then 6.

“You start panicking because you have basically tried everything on the myeloma menu at that point — is there anything left?” Guillaume says. Thanks to MSK, there was.

CAR T Cell Therapy for Relapsed Multiple Myeloma Takes Aim at New Target: GPRC5D

Dr. Giralt told Guillaume about a clinical trial testing a new treatment called chimeric antigen receptor (CAR) T cell therapy. Often called a living drug, the treatment involves removing immune cells called T cells from the blood and inserting a new gene into those cells, which enables them to recognize the cancer.

The clinical trial, led by MSK multiple myeloma specialist Sham Mailankody, MBBS, took a novel approach: It was targeting an antigen on the surface of the myeloma cells called GPRC5D. Previous CAR T cell therapies for multiple myeloma had targeted a different antigen — called BCMA. But BCMA-targeted therapies don’t work for everyone, especially those who have received many previous treatments.

“One of MSK’s great strengths is our ability to develop new immunotherapy treatment options for people who, like Guillaume, appear to have exhausted all other available therapies,” Dr. Mailankody says.

Indeed, there was exciting research underway in an MSK lab, which reported in 2019 that GPRC5D could be a promising multiple myeloma target. Scientists used a specialized staining technique to reveal GPRC5D antigens all over the surface of myeloma cells. Soon thereafter in 2020, MSK launched a phase 1 clinical trial at MSK, led by Dr. Mailankody.

“It’s a testament to the clinical, translational, and laboratory teams at MSK that we were able to take that preclinical lab data and open the first human study very quickly,” Dr. Mailankody says.

The Multiple Myeloma CAR T Cell Clinical Trial That Renewed Hope for Guillaume

Guillaume jumped at the chance to join the trial. “We didn’t think twice. I was absolutely convinced that they were doing what was best for me and my family,” he says.

MSK patient Guillaume Arnould seen outdoors with his wife and son.

Guillaume (center) with his wife, Ruth, and son, Tristan

In January 2021, Guillaume received his CAR T cells, which had been engineered to attack this new target. Although he needed chemotherapy first, it was a milder dose than for his previous stem cell transplants. After seven years of being in hospitals, Guillaume had built up a tolerance for the pain and discomfort, and he made sure to exercise diligently throughout treatment.

“I discovered CrossFit and I love it — I work out almost every day,” he says. “It is important to have something to clear your mind and get it off the cancer.”

Guillaume was able to return to work as a fund manager in April 2021. His disease is currently stable. Guillaume is checked regularly with scans and other tests in Manhattan and at MSK Westchester, not far from his home in Larchmont, New York.

The Future of BCMA- and GPRC5D-Targeted Immunotherapy for Multiple Myeloma

GPRC5D continues to offer promise for patients with multiple myeloma. In September 2022, Dr. Mailankody reported encouraging results from the phase 1 trial in The New England Journal of Medicine. In addition, a new trial has opened at MSK, to give BCMA- and GPRC5D-targeted CAR T cell therapies together, for patients with advanced myeloma.

“We are continuing to explore possible combination approaches with this therapy, as well as understand how resistance may develop,” Dr. Mailankody says.

More than two and a half years after the cutting-edge treatment, Guillaume continues to enjoy life with Ruth and Tristan, now 9. “I owe so much to my family in their continuous support through these challenging years and helping me to keep up my fighting spirit and not give up,” Guillaume says. “I’m also extremely grateful to Dr. Giralt, Dr. Mailankody, and all the nurses and support staff at MSK. Their devotion and passion are inspiring.”

Dr. Giralt and his colleagues’ research receives essential philanthropic support from the MSK Giving community, including the A.C. Israel Foundation, Inc.

Dr. Giralt holds the Melvin Berlin Family Chair in Multiple Myeloma.