ASH: J&J, Legend's anti-BCMA CAR-T keeps it consistent in phase 2 as FDA filing looms

Bristol Myers Squibb and bluebird bio were first to file an anti-BCMA CAR-T for approval, but Johnson & Johnson and Legend Biotech are hot on their heels. The duo unveiled the first phase 2 data for its prospect, which banished multiple myeloma in two-thirds of patients and shrank tumors in 97% of patients. J&J plans to file the treatment for FDA approval by the end of the year.

The data, presented virtually Saturday at the annual meeting of the American Society of Hematology, come from 97 patients whose cancer had returned after a median of six prior treatments or had not responded to treatment in the first place. The investigators followed the patients for a median of one year after treatment. J&J’s Janssen unit previously reported data from 29 patients from the phase 1b part of the trial, showing the treatment—ciltacabtagene autoleucel, or cilta-cel—eliminated tumors in 86% of patients and shrank tumors in all 29 of them for a 100% overall response rate.

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“Of course, it’s difficult to beat that number, but we are pleased to report that now, when we include all 97 patients in the CARTITUDE-1 trial, the overall response rate remains very high at 97%,” said Ying Huang, Ph.D., CEO and chief financial officer of Legend Biotech. “After a median follow-up of 12.4 months, we still see a 67% stringent complete response rate that is very consistent with the data reported at ASCO 2020 and ASH 2019,” Huang added, referring to a response rate defined by the absence of two key markers of myeloma in the blood and bone marrow.

“I’ll summarize the data with one single word: consistency,” Huang said.

The median duration of response had not been reached, meaning that more than half of the patients were still responding to treatment after one year. The median progression-free survival had not been met either, indicating that more than half of the patients had not seen their disease worsen over that same time frame. At the one-year mark, 89% of the patients were still alive, and 77% of the patients had not seen their cancer progress.

It’s good news for a patient group that has been failed by all available treatment options. Those include proteasome inhibitors such as Amgen’s Kyprolis and Takeda and J&J’s Velcade, immunomodulatory drugs including BMS’ Revlimid and Pomalyst and anti-CD38 antibodies like J&J’s Darzalex.

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“If you look at those patients who have tried and failed all three major classes of drugs, any other treatment as a monotherapy would usually yield progression-free survival of about four months,” Huang said. With about three-quarters of patients still alive a year after treatment, cilta-cel may offer a “pretty significant improvement” over the four months typically seen in last-line myeloma treatment, he said.

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The most common side effects investigators flagged were neutropenia, an abnormally low white blood cell count, and cytokine release syndrome (CRS), which happens when CAR-T works too well and activates the immune system too strongly. Though 95% of the patients suffered CRS, the vast majority (95%) of the cases were mild. Of the 14 patients who died in the study, one died from CRS. Five patients died because their cancer worsened, while the remaining eight died from other side effects including sepsis, pneumonia and neurotoxicity.

As seen in earlier data, CRS predictably came on about a week after treatment—later than it usually does with other CAR-T therapies—with nearly all cases (99%) resolved in the first two weeks. Because of that timeline, J&J and Legend figure they may not need to keep patients in the hospital for monitoring after treatment, instead sending them home and bringing them back again only on an as-needed basis.

“Pending FDA approval, J&J and Legend could potentially explore cilta-cel treatment in an outpatient setting,” Huang said, which would be a "welcome development for patients."

Outpatient treatment also has the potential to "relieve hospitals of a lot of burden, including the physicians and nurses you require to take care of and monitor those patients," as well as to free up ICU space for other patients, he added.