Conference Coverage

Durable responses with anti-BCMA CAR T-cell for multiple myeloma


 

FROM ASH 2020

High ORR

The ORR was 96.9% (94 of 97 patients), comprising 67% stringent complete responses (sCR), 25.8% very good partial responses (VGPR), and 4.1% partial responses (PR).

Among 57 patients evaluable for minimal residual disease (MRD), 53 (93%) were MRD negative. Of this group, 49 had a VGPR or better.

The median time to first response was 1 month (range 0.9 to 8.5 months). At the time of data cutoff 70 patients had an ongoing response.

Among patients followed for a minimum of 6 months, most had cilta-cel CAR T-cells below the level of quantification (2 cells per microliter) in peripheral blood.

At a median follow-up of 12.4 months, 12-month overall progression-free survival rate was 76%, with the median PFS not reached. The 12-month overall survival rate was 88.5%, with the median OS not reached.

Safety data

All patients had at least one hematologic adverse event, 96 of which were grade 3 or 4 in severity. The events include neutropenia, anemia, thrombocytopenia, leukopenia, and lymphopenia. The median time to recovery was 2 weeks for grade 3 or 4 neutropenia and 4 weeks for thrombocytopenia.

Infections of any grade occurred in 57.7% of patients, including grade 3/4 pneumonia in 8.2% and grade 3/4 sepsis in 4.1%.

Grade 3 or 4 nonhematologic toxicities were uncommon, Dr. Madduri noted.

CRS of any grade occurred in 92 patients, but only 4 had grade 3 or 4 CRS.

Neurotoxicities occurred in 20 patients, of whom 10 had grade 3 or 4 neurotoxicity.

Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 16 patients, with 2 having grade 3 or greater ICANS. Other neurotoxicities of any grade, many which overlapped with ICANS, occurred in 12 patients, with 9 having grade 3 or 4 neurotoxicity.

The median time to ICANS onset was 8 days, with a median time to recovery of 4 days. Other neurotoxicities took longer to manifest and disappear, however, with a median time to onset of 27 days, and median time to recovery of 75 days.

Neurotoxicity mechanism questioned

In the question-and-answer session following her presentation, an audience member asked whether the investigators had any insights into the mechanism underlying the non-ICANS neurotoxicities they saw.

“We saw no clear etiology in the other neurotoxicities, but we saw that maybe there could be some mild associations with high tumor burden, prior CRS, ICANS, or even the higher expansion and persistence of these cells,” Dr. Madduri replied.

She noted that subsequent to these findings, the investigators have implemented mitigation strategies including allowing patients to have more bridging chemotherapy, more aggressive steroid use for early ICANS, and extensive monitoring.

Eric Smith, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said that the non-ICANS neurotoxicity profile of cilta-cel was different from that seen in other CAR T-cell trials, and asked how it compared to that of bi-specific BCMA/CD3 CAR T constructs.

“We did see some nerve palsies and peripheral motor neuropathy, but it wasn’t that many patients, and it’s really hard to compare what happened here with the bi-specifics, as every product is very different,” she said.

The study was sponsored by Janssen Research & Development and Legend Biotech. Dr. Madduri disclosed honoraria, consultancy, and speakers bureau activities for those companies and others.

SOURCE: Madduri D et al. ASH 2020. Abstract 177.

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