ASCO: Bristol Myers' anti-BCMA CAR-T tackles multiple myeloma in patients out of options

Bristol Myers Squibb’s BCMA-targeting CAR-T therapy shrank tumors in nearly three-quarters of relapsed multiple myeloma patients and eliminated them in one-third. And the treatment, picked up in the company’s $74 billion Celgene buyout, could help patients who are “truly at the end of treatment options."

The study tested three dose levels of the bluebird bio-partnered treatment, idecabtagene vicleucel, or ide-cel, in 128 patients whose multiple myeloma returned after treatment or didn’t respond in the first place. The patients had tried a median of six other treatments, including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody such as Johnson & Johnson’s Darzalex.

In addition to shrinking tumors in 73% and clearing tumors in 33% of patients, the treatment staved off cancer for a median 8.8 months and extended patients’ lives by a median of 19.4 months. One year after treatment, 78% of the patients were still alive. The results will be presented at the virtual annual meeting of the American Society for Clinical Oncology.

RELATED: Bluebird nabs $200M in early payout from retooled Bristol Myers BCMA deal

“When we think about patients with relapsed or refractory multiple myeloma, there are no treatment options that are standard of care for late-line therapy,” Bristol Myers’ Chief Medical Officer Samit Hirawat told FierceBiotech. Despite the host of medicines available to treat multiple myeloma, including BMS’ own Pomalyst—also picked up in the Celgene deal—the cancer is still incurable. Patients eventually relapse, and more than 12,000 Americans die from multiple myeloma each year.

“The overall outcome is certainly transformational, with 73% of patients responding,” he added.

And that’s not all. Complete responders, that is, patients whose cancers disappeared after treatment, fared significantly better than the general study population. Ide-cel kept cancer at bay for 20.2 months in those patients, more than double the 8.8 months logged for the overall population. The duration of response was similar: 19 months for the complete responders versus 10.7 months for the general population. Bristol Myers aims to figure out why those patients do so well so it can get ide-cel to the patients most likely to benefit.

RELATED: With Bristol Myers' latest CAR-T filing, Celgene investors inch closer to payout

“Now that BCMA as a target is getting validated, we continue to look at the identification of patients who are going to have better outcomes. Translational research is going to become very, very important,” Hirawat said.

Most of the patients (84%) suffered cytokine release syndrome (CRS), a well-known side effect of CAR-T therapy where the engineered T cells work too well and activate the immune system too strongly. But most of those cases were mild; only one patient died and seven patients—6%—needed aggressive treatment for CRS.  Less than one-fifth of the patients had neurological side effects.

The safety data are encouraging, with the side effects “certainly on a much lower level in terms of the severity scale,” Hirawat said. As it continues to evaluate ide-cel and its lymphoma CAR-T, lisocabtagene maraleucel, Bristol Myers will be on the lookout for ways to identify patients who are predisposed to CRS.

“We think we are making true advances in providing a safe medicine for these patients, but we have some ways to go in terms of learning and improving the overall safety profile,” Hirawat said.

BMS and bluebird filed ide-cel for FDA review in March but hit an embarrassing snag Wednesday when the FDA refused to consider the filing due to manufacturing concerns. The duo plan to refile by July and analysts smooth sailing from there.

"[We] believe ide-cel continues to show strong efficacy in a tough treatment setting, and expect approval and likely priority review following resubmission," wrote SVB Leerink analyst Mani Foroohar in an investor note.

Ide-cel isn’t the only anti-BCMA treatment in the multiple myeloma pipeline. Johnson & Johnson is working on a CAR-T therapy, JNJ-4528, which shrank multiple myeloma tumors in all 29 of the patients in a small trial presented at the annual meeting of the American Society of Hematology in December. That same month, GlaxoSmithKline filed its antibody-drug conjugate, belantamab mafodotin, for FDA approval. The treatment shrank tumors in about one-third of 100 patients with advanced multiple myeloma.