Susan Bal, MD, assistant professor, Hematology, Medical Oncology, University of Alabama at Birmingham (UAB), UAB Health, O’Neal Comprehensive Cancer Center, discusses the clinical implications for the use ofciltacabtagene autoleucel (cilta-cel; Carvykti) in patients with relapsed/refractory multiple myeloma.

 for the treatment of adult patients with relapsed/refractory multiple myeloma following 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. This made cilta-cel the second CAR T-cell therapy approved in the multiple myeloma space, following 

idecabtagene vicleucel (ide-cel; Abecma), which was FDA approved in March 2021

The approval of cilta-cel was supported by data from the phase 1b/2 CARTITUDE-1 trial (NCT03548207), where patients were treated with a single infusion at a target dose of 0.75 x 106 CAR-positive viable T cells/kg (range, 0.5 x 106-1.0 x 106).

The baseline characteristics of the patients enrolled in this study were similar to those included in the phase 2 KarMMA trial (NCT03361748), which supported the FDA approval of ide-cel, Bal says. Notably, 88% of patients were triple-class refractory, and 99% were refractory to their last lane of therapy received.

Although 95% of patients in the cilta-cel arm experienced any-grade cytokine release syndrome (CRS), only 5% of patients had grade 3 or higher CRS. Among 97 patients who received cilta-cel during the trial, immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 23% of patients. Three patients had grade 3 or 4 ICANS, and 2 patients had grade 5 ICANS. Late onset neurotoxicity, such as peripheral neuropathies and neurocognitive changes, were also reported, Bal expands.

To better understand the differences between cilta-cel and ide-cel, ongoing monitoring of evaluable patients is required, Bal details. Treating clinicians continue to be excited with the efficacy that has been seen with these FDA-approved CAR T-cell therapies in clinical practice, Bal concludes.

Videos

Susan Bal, MD, discusses the clinical implications for the use of ciltacabtagene autoleucel in patients with relapsed/refractory multiple myeloma.


Dr Bal on the Clinical Implications of Cilta-cel in R/R Multiple Myeloma

Susan Bal, MD, assistant professor, University of Alabama at Birmingham, discusses key efficacy and safety data from the phase 2 KarMMa trial (NCT03361748) in patients with relapsed/refractory multiple myeloma.

The second-generation CAR T-cell product idecabtagene vicleucel (ide-cel; Abecma) was the first anti-BCMA CAR T-cell therapy to be FDA approved for patients with relapsed/refractory multiple myeloma. This product, which was granted FDA approval on March 26, 2021, has a CD3 zeta cell activation domain and has a costimulatory domain from 4-1BB. The FDA approval of ide-cel was based on findings from the KarMMa trial, which evaluated the efficacy and safety of this agent at doses ranging from 150 x 10

KarMMa enrolled 140 patients, 128 of whom received ide-cel. In total, 84% of the treated patients were triple-class refractory, and the median age was 61 years, which is younger than the typical median age of patients with multiple myeloma, Bal says. The treated population had received a median of 6 prior lines of therapy.

CAR T-cell therapy has unique adverse effects, including cytokine release syndrome (CRS), which 84% of patients experienced in the trial, Bal notes. However, the CRS events observed in this trial were mostly grade 1 or 2, with 5 patients experiencing grade 3 CRS and 1 patient each experiencing grades 4 and 5 CRS.

Neurotoxicities were also observed in this study, but at a lower frequency than is often seen in patients with lymphoma, Bal explains. Overall, 18% of patients experienced any-grade neurotoxicity, and 3% of patients experienced grade 3 neurotoxicity.

In total, ide-cel generated an overall response rate (ORR) of 73% in the overall study population and an ORR of 81% in patients who had received the highest dose level. Additionally, 33% of patients in the overall population achieved a complete response.

The median progression-free survival was 8.8 months in the entire study population and 12.1 months in the patients who received the highest dose level. Furthermore, the median overall survival was 19.4 months in the entire study population, Bal concludes.

Susan Bal, MD, assistant professor, University of Alabama at Birmingham, discusses key efficacy and safety data from the phase 2 KarMMa trial in patients with relapsed/refractory multiple myeloma.

Dr Bal on Ide-cel in R/R Multiple Myeloma

Susan Bal, MD, assistant professor, Hematology, Medical Oncology, University of Alabama at Birmingham (UAB), UAB Health, discusses unmet needs with CAR T-cell therapy in multiple myeloma.

Improving the durability of responses for patients with multiple myeloma who receive CAR T-cell therapy remains an area of need, Bal begins. Although CAR T-cell therapy can elicit early responses that deepen within the first month of treatment, patients continue to relapse, and a plateau has not been observed on progression-free survival curves, Bal adds.

Additionally, the 2 CAR T-cell therapies currently approved by the FDA—idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti)—are both BCMA-targeted agents. Treatment strategies for patients who relapse following one of these CAR T-cell therapies still need to be improved, and exploring other targets for CAR T-cell therapy in multiple myeloma, such as GPRC5D, remains a key area of interest, Bal says. She notes that data presented in 2022 on MCARH109, a CAR T-cell therapy targeting the GPRC5D, showed that the CAR T-cell therapy elicited remissions in patients with relapsed/refractory multiple myeloma.

As agents directed at different targets emerge, understanding how to sequence these therapies will be vital, Bal says. For example, patients who have received prior BCMA-directed CAR T-cell therapy have been shown to respond to an agent targeting GPRC5D, she says.

Notably, the BCMA- and CD3-targeted bispecific antibody teclistamab-cqyv (Tecvayli) was approved by the FDA in October 2022 for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 previous lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, which is the same indication as ide-cel and cilta-cel.

Since teclistamab also targets BCMA, questions remain regarding the sequencing of the bispecific antibody and CAR T-cell therapy, and future investigations will need to look at the kinetics of how patients perform when they are first treated with CAR T-cell therapy vs a bispecific antibody, Bal concludes.

Susan Bal, MD, discusses unmet needs with CAR T-cell therapy in multiple myeloma.


Dr Bal on Unmet Needs With CAR T-cell Therapy in Multiple Myeloma

Susan Bal, MD, assistant professor, Hematology, Medical Oncology, University of Alabama at Birmingham (UAB), UAB Health, discusses the evolution of CAR T-cell therapy in multiple myeloma.

 State of the Science Summit™, Bal highlighted key updates across the multiple myeloma treatment landscape, specifically focusing on CAR T-cell therapy. The emergence of CAR T-cell therapy has represented a notable treatment advancement across hematologic malignancies, including multiple myeloma, Bal begins. Currently, there are 2 CAR T-cell therapies approved by the FDA for patients with relapsed/refractory multiple myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody: idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti). The phase 2 KarMMA trial (NCT03361748) 

led to the FDA approval of ide-cel in March 2021

, and data from the phase 1b/2 CARTITUDE-1 trial (NCT03548207) 

supported the FDA approval of cilta-cel in February 2022

Outcomes from these 2 pivotal trials showed high and durable response rates in heavily pretreated patient populations, Bal continues. Trials exploring ide-cel and cilta-cel in earlier lines of therapy, where patients are generally more fit and have a stronger immune system, could lead to higher response rates, Bal expands.

Ide-cel and cilta-cel are both BCMA-targeted CAR T-cell therapies; however, novel CAR T-cell therapies directed at other targets, such as GPRC5D, are being explored, and these agents could provide additional options for patients with multiple myeloma, particularly those who have experienced disease progression on approved therapies, Bal explains. The exploration of novel targets and the use of CAR T-cell therapy in earlier lines of treatment could stand to improve treatment options for patients with multiple myeloma, Bal concludes.

Susan Bal, MD, discusses the evolution of CAR T-cell therapy in multiple myeloma.


Susan Bal, MD, O'Neal Comprehensive Cancer Center at UAB

Articles

Dr Bal on the Clinical Implications of Cilta-cel in R/R Multiple Myeloma

Dr Bal on Ide-cel in R/R Multiple Myeloma

Dr Bal on Unmet Needs With CAR T-cell Therapy in Multiple Myeloma

Dr Bal on the Evolution of CAR T-cell Therapy in Multiple Myeloma