Updated Data from KarMMA-3 Show Improved PFS in Relapsed/Refractory Myeloma (2024)

Survival appears to be significantly improved when idecabtagene vicleucel is given vs standard of care in relapsed/refractory multiple myeloma.

Updates from the phase 3 KarMMa-3 trial (NCT03651128) investigating idecabtagene vicleucel (ide-cel; Abecma) vs standard of care (SOC) combination regimens for relapsed/refractory multiple myeloma after 2 to 4 lines of therapy showed significant improvement in the trial’s primary end point of progression-free survival favoring the experimental arm.1,2

Updated Data from KarMMA-3 Show Improved PFS in Relapsed/Refractory Myeloma (1)Updated Data from KarMMA-3 Show Improved PFS in Relapsed/Refractory Myeloma (2)

"These results will allow use of [idecabtagene vicleucel] in patients wtih suboptimal treatment options," according to the lead author of the phase 3 KarMMa-3 trial.

Updated Data from KarMMA-3 Show Improved PFS in Relapsed/Refractory Myeloma (3)

The updated results were presented at the 5th European CAR T-cell Meeting, and simultaneously published in The New England Journal of Medicine. At a median follow-up of 18.6 months, the progression-free survival (PFS) was 13.3 months (95% CI, 11.8-16.1) compared with 4.4 months (95% CI, 3.4-5.9) in the SOC arm (HR, 0.49; 95% CI, 0.38-0.65; P <.001). At 6 months, the PFS rate was 73% in the ide-cel arm vs 40% in the SOC arm, and the 12-month PFS rates were 55% vs 30%, respectively.

A supplemental biologics license application is expected to be submitted to the FDA in 2023.

“These data will impact clinical practice. It is the first phase 3 trial demonstrating PFS benefit for a [B-cell maturation agent] BCMA CAR vs standard regimens in an early disease setting in patients who have already been exposed the 3 main classes of anti-myeloma drugs—namely, immunomodulatory drugs, proteosome inhibitors, and anti-CD38 monoclonal antibodies,” lead author, Paula Rodríguez Otero, MD, PhD, medical coordinator of the Central Unit for Clinical Trials at Clinica Universidad de Navarra, Pamplona, Spain, said in a comment to CancerNetwork®.

“These results will allow early use of ide-cel in patients with suboptimal treatment options.”

A total of 254 patients were randomly assigned to the ide-cel arm vs 132 in the SOC arm. Baseline characteristics were well balanced, except for Black race, which comprised 7% of patients in the ide-cel arm vs 14% of those in the SOC arm. Additionally, 42% vs 46% had high-risk cytogenetic abnormalities.

The median time since diagnosis was 4 years, and the median time to progression on a previous antimyeloma therapy was 7 months. Additionally, patients received an average of 3 prior therapies. Moreover, 90% of patients were refractory to immunomodulatory agents and 74% were refractory to proteasome inhibitors. Sixty-five percent of patients in the ide-cel arm vs 67% in the SOC arm were triple-class refractory.

A partial response or better was observed in 71% of patients in the ide-cel arm (95% CI, 66%-77%) vs 42% (95% CI, 33%-50%) in the SOC arm (Odds ratio [OR], 3.47; 95% CI, 2.24-5.39; P <.001). A complete response (CR) or stringent CR or higher was observed in 39% of patients in the ide-cel arm vs 5% in the SOC arm.

Patients had a median time to response of 2.9 months in the ide-cel arm and 2.1 months in the SOC arm, and the median duration of response was 14.8 months (95% CI, 12.0-18.6) vs 9.7 months (95% CI, 5.4-16.3) in each respective arm. The minimal residual disease negativity status within 3 months prior to the occurrence was observed in 20% of patients in the ide-cel arm and 1% in the SOC arm.

The overall survival data were immature and still blinded at data cutoff.

In terms of safety, grade 3/4 adverse effects (AEs) were observed in 93% of patients in the ide-cel group and 75% in the SOC group, while 14% vs 6% had grade 5 AEs, respectively. Common any-grade hematologic AEs in each respective arm included neutropenia (78% vs 44%), anemia (66% vs 36%), and thrombocytopenia (54% vs 29%) in the ide-cel and SOC arms, respectively.

Among those in the ide-cel group whose grade 3/4 thrombocytopenia lasted 1 month or longer, the median time to recovery was 1.9 months (95% CI, 1.5-2.1) and 1.7 months (95% CI, 1.5-1.9) for neutropenia.

Infection occurred in 58% of patients in the ide-cel arm and 54% in the SOC arm. Grade 3/4 events of infection were observed in 24% vs 18% and grade 5 AEs in 4% vs 2% in the ide-cel and SOC arms, respectively. The most common infections were upper respiratory tract infection in 12% vs 7%, and pneumonia in 10% vs 7% in the ide-cel and SOC arms, respectively.

Serious AEs of grade 5 or higher occurred in 3% vs 1%, the most common of which was sepsis in 2% vs 1% of those in the ide-cel and SOC arms, respectively.

Grade 3/4 cytokine release syndrome (CRS) occurred in 4% of patients, and 1% was grade 5. The cause of death included a decline of organ function and concomitant grade 5 candida-related sepsis. The median time to CRS was 1 day and it lasted a median of 3.5 days.

Of note, 30% of patients in the ide-cel group and 26% in the SOC group died. The most common cause of death was disease progression in 17% of patients in both groups, respectively.

“There is a full portfolio of studies evaluating BCMA CAR T-cell therapies and particularly ide-cel in other settings of clinical need, such as patients with a suboptimal response after frontline therapy, patients with high-risk disease in addition to autologous stem cell transplant, frontline multiple myeloma. Surely the next steps will be to evaluate these potent therapies as part of the frontline treatment of myeloma patients aiming for a cure for this disease,” Otero concluded.

References

  1. Abecma (idecabtagene vicleucel) reduced the risk of disease progression or death by 51% versus standard regimens in earlier lines of therapy for relapsed and refractory multiple myeloma based on results from phase 3 KarMMa-3 study. News release. Bristol Myers Squibb. February 10, 2023. Accessed February 10, 2023. https://bit.ly/3XkmJYo
  2. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. February 10, 2023. doi:10.1056/NEJMoa2213614
Updated Data from KarMMA-3 Show Improved PFS in Relapsed/Refractory Myeloma (2024)

FAQs

What does relapsed refractory multiple myeloma mean? ›

According to the criteria developed by the International Myeloma Working Group (IMWG), relapsed refractory MM (RRMM) is defined as a progressive disease, poor response despite treatment, progression within 60 days of the most recent treatment in a patient who had achieved remission, the absence of at least minimal ...

What is the prognosis for refractory multiple myeloma? ›

In one study of nearly 13,000 people with relapsed/refractory multiple myeloma, half were still alive 32.4 months after beginning their second round of treatment. Recent advances in treatment have helped people with RRMM live longer than before.

How do you treat refractory myeloma? ›

Treatment can include the following drugs and combinations: Bortezomib (Velcade®), lenalidomide (Revlimid®), dexamethasone. Carfilzomib (Kyprolis®), dexamethasone. Carfilzomib, lenalidomide, dexamethasone.

What are the new treatments for relapsed multiple myeloma? ›

Rye Brook, N.Y., August 16, 2023 – The U.S. Food and Drug Administration (FDA) in August approved both talquetamab-tgvs (Talvey™) and elranatamab (Elrexfio™) to treat adults with multiple myeloma that has failed to respond or has relapsed despite previous treatments.

What is the difference between relapsed and refractory disease? ›

What are relapsed and refractory diseases? Relapsed disease means a cancer has come back. Refractory disease means a cancer has stopped responding to treatment. “Most hematologic cancers, like leukemia, lymphoma, and multiple myeloma, are initially very sensitive to treatment.

What does refractory mean in medical terms? ›

(reh-FRAK-tor-ee) In medicine, describes a disease or condition that does not respond to treatment.

What is the survival rate for relapsed myeloma? ›

Each subsequent relapse can be more difficult to treat. In the same 2016 study, the median overall survival in patients who received a stem cell transplant and relapsed within 12 months was 23.1 months, compared to 122.2 months in those who relapsed after 12 months.

What is the average time for multiple myeloma relapse? ›

In a 2016 study, 16 percent of people with multiple myeloma relapsed within one year. After about four years, almost 66 percent of participants had experienced a relapse.

What is the best prognostic factor for multiple myeloma? ›

Traditional prognostic factors in MM measure plasma cell proliferation (plasma cell labeling index, Ki-67), plasma cell mass (clinical stage, plasmacytosis), or the status of the patient (hemoglobin, calcium, creatinine, albumin).

What is the miracle drug for multiple myeloma? ›

Daratumumab is a targeted cancer drug that kills multiple myeloma cells and also recruits immune cells to help kill cancer cells. It can be infused through a vein (intravenous) or injected under the skin (subcutaneous).

Is refractory multiple myeloma a rare disease? ›

Multiple myeloma is a rare cancer that affects the blood and bones. It is the second most common form of blood cancer in the United States, yet it is still considered a rare disease.

Has anyone ever recovered from myeloma? ›

Is multiple myeloma curable? Multiple myeloma is currently not curable, but we can manage the disease effectively for years. For active myeloma, treatment may include chemotherapy, proteasome inhibitors, immune-modifying drugs or other medications, or stem cell transplantation.

What is the new treatment for multiple myeloma in 2024? ›

Idecabtagene vicleucel (ide-cel; Abecma) received FDA approval in April 2024 for the treatment of adult patients with relapsed/refractory multiple myeloma following 2 or more prior lines of therapy, including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody.

What is the new hope for multiple myeloma? ›

The development of P-BCMA-101 CAR T-cells brings hope for improving the treatment outcomes and quality of life for patients with multiple myeloma, paving the way for a new era of personalized and targeted cancer therapies [54].

What is an aggressive relapse of multiple myeloma? ›

Types of Relapse

There are two types of multiple myeloma relapses, and doctors handle them differently: Indolent or low risk: This happens more slowly, often over years. Your doctor might try a treatment you've already had. Aggressive or high risk: This one comes up quickly, within weeks or months.

How many times can you relapse with multiple myeloma? ›

Relapses can happen several times during the course of the disease.

What is relapsed refractory lymphoma? ›

The term “relapsed” refers to disease that reappears or grows again after a period of remission. The term “refractory” is used to describe when the lymphoma does not respond to treatment (meaning that the cancer cells continue to grow) or when the response to treatment does not last very long.

What is the difference between relapsed and refractory AML? ›

Relapsed, or recurrent, acute myeloid leukemia (AML) means the leukemia has come back after treatment and remission. Refractory AML means the leukemia did not respond to treatment. Complete remission has not been reached because the chemotherapy drugs did not kill enough leukemia cells.

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