Deep and Durable Responses Ide-Cel CAR T Shows Promise for High-Risk Multiple

Study Shows Promising Results in Treating High-Risk Multiple Myeloma with Ide-cel

A cohort study of the KarMMa-2 trial discovered promising and durable responses in patients with high-risk multiple myeloma treated with ide-cel.

The Study Results

The overall response rate (ORR) in those who had a response but were treated in the frontline setting was 80.6% (95% CI, 62.5%-92.5%) vs 93.5% (95% CI, 78.6%-99.2%) in those with responses to ide-cel. Between both groups, the complete response (CR) rate was 3.2% (95% CI, 0.1%-16.7%) vs 71.0% (95% CI, 52.0%-85.8%).

Minimal residual disease (MRD) was assessed between 3 and 36 months following treatment with ide-cel. At 3 months, 11% of patients were MRD-positive, 11% were MRD-intermediate, and 79% were MRD-negative. Subsequently, at 6 months, MRD rates showed 18% were MRD-positive and 82% were MRD-negative; 19% vs 81% at 12 months; 20% vs 80% at 18 months; 18% vs 82% at 24 months; and 25% vs 75% at 36 months.

The rate of ongoing responses at 24 months was 65.3% in patients with a response vs 75.7% in patients with a CR or better. The progression-free survival rate at 12 months was 70.0%; at 24 months, it was 63.3%. The overall survival (OS) rate at 12 months was 89.9% vs 78.9% at 24 months.

Expert Opinion

“Although a high proportion of patients had high tumor burden and high-risk cytogenetics, response rates were high,” says Xavier Leleu, MD, MSc, PhD, head of the Myeloma Clinic at Poitiers University Hospital in Lille France, during a presentation of the data.

The Cohort

Cohort 2b included 35 patients with an early relapse. Patients needed to have received frontline therapy with a proteasome inhibitor, immunomodulatory drug, and dexamethasone; have measurable disease; and have an ECOG performance status of 0 or 1 to be included. Ide-cel was given at 150 to 450 x 106 CAR-positive T cells.

The End Points and Secondary End Points

The primary end point was CR rates by investigator assessment per the International Myeloma Working Group criteria. Secondary end points included ORR, time to response, duration of response, PFS, OS, and safety. The exploratory end points were MRD negativity and biomarkers.

The Patients

At the data cutoff of December 13, 2023, the median follow-up was 30.1 months. During this time, 64.5% of patients were still on study treatment. Reasons for discontinuation included death (22.6%), withdrawal by patient (9.7%), or physician decision (3.2%). The median patient age was 60 years old, with 41.9% of patients being 65 years or older and 29.0% being 70 years or older. The median time to progression during frontline therapy was 7.1 months, and 45.2% of patients had a high tumor burden. Additionally, 38.7% of patients were high-risk, and 16.1% were ultra-high-risk. Extramedullary disease was noted in 12.9% of patients, 67.7% were double-class refractory, 16.1% were triple-class refractory, and 16.1% were triple-class exposed.

The Treatment

As frontline therapy, most patients (38.7%) received bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone plus bortezomib, thalidomide, and dexamethasone; or other (41.9%) treatment. Of note, 87.1% of patients received any type of bridging therapy.

The Side Effects

Grade 3 or higher adverse effects (AEs) were noted in 93.5% of patients. The most common hematologic AEs included neutropenia (93.5%), anemia (54.8%), thrombocytopenia (35.5%), lymphopenia (45.2%), and leukopenia (38.7%). Of note, 6.5% of patients had arthralgia, 12.9% had metabolism and nutrition disorders, 6.5% had gastrointestinal disorders, and 6.5% had nervous system disorders. Additionally, 19.4% of patients had infections or infestations. The median time to recovery was 1.5 months (95% CI, 1.3-1.5) for grade 3/4 neutropenia and 2.0 months (95% CI, 1.4-not evaluable) for thrombocytopenia.

The Results of Quality of Life Studies

The European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire found patient-reported improvement in overall quality of life. There was a clinically meaningful improvement by month 3 in 85% or more of patients.

Related Studies and Advancements

A study found that glofitamab plus gemcitabine and oxaliplatin significantly improved survival in patients with relapsed/refractory diffuse large B-cell lymphoma who were not eligible for stem cell transplant.

In addition, ciltacabtagene autoleucel has been recently approved by the FDA for the treatment of relapsed/refractory multiple myeloma. The CARTITUDE-4 study found that treatment with cilta-cel led to a statistically significant and clinically meaningful improvement in overall survival among patients with relapsed and lenalidomide-refractory multiple myeloma who received 1 to 3 prior lines of therapy.

Minimal residual disease monitoring is an important aspect of myeloma treatment and advancements have been made in this area with ClonoSeq. In this episode of Targeted Talks, Ben Derman, MD, dissects the latest advancements in myeloma treatment, focusing on the role of ClonoSeq and minimal residual disease monitoring.

Blinatumomab integration has shown to lead high complete response and minimal residual disease-negativity rates, especially in patients over 40 and Philadelphia chromosome-positive cases.

Conclusion

The study results of using ide-cel to treat high-risk multiple myeloma have shown promising and durable responses. While there are some adverse effects, patient-reported improvement in overall quality of life has also been observed. Ongoing research and advancements in myeloma treatment, including minimal residual disease monitoring and the use of other therapies like ciltacabtagene autoleucel and blinatumomab integration, give hope for improved outcomes in treating this challenging disease.

Originally Post From https://www.targetedonc.com/view/deep-and-durable-responses-ide-cel-car-t-shows-promise-for-high-risk-multiple-myeloma-relapse