Pooja Phull, MD, is a hematologist/oncologist at John Theurer Cancer Center, Hackensack University Medical Center.

Pooja Phull, MD, discusses the rationale for assessing CAR T-cell therapy in the real-world vs trial setting in relapsed/refractory multiple myeloma.

Dr Phull on the Rationale for the Retrospective Analysis of CAR T-Cell Therapy in R/R Myeloma

“It's important to see how [clinical trial data] compare to our real-world outcomes in our [patients with] multiple myeloma in the clinic that we're seeing every day, now that [the CARTITUDE-1 and KarMMA-1] trials have really matured, and we have a lot of long-term data on them.”

Pooja Phull, MD, hematologist/oncologist, John Theurer Cancer Center, Hackensack University Medical Center, discusses the rationale for assessing ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma) in real-world patients with relapsed/refractory multiple myeloma.

Within the past few years, CAR T-cell therapy has helped improve the treatment paradigm for patients with multiple myeloma in the short and long term, Phull begins. She notes that follow-up data from the phase 1b/2 CARTITUDE-1 (NCT03548207) and phase 2 KarMMA-1 (NCT03361748) trials have now matured, which provides a clearer picture of the respective long-term data.

Of note, the CARTITUDE-1 trial evaluated cilta-cel in heavily pretreated patients with relapsed/refractory multiple myeloma. At a median follow-up of 33.4 months, the median duration of response (DOR), progression-free survival (PFS), and overall survival were 33.9 months (95% CI, 25.5-not estimable [NE]), 34.9 months (95% CI, 25.2-NE), and not reached, respectively, according to final results of the study.

The KarMMA-1 study investigated ide-cel in patients with relapsed/refractory multiple myeloma. At a median follow-up of 13.3 months, 73% of patients (n = 94/128) experienced a response, of which 33% had a complete response or better. Notably, the median DOR, PFS, and OS were 10.7 months (95% CI, 9.0-11.3), 8.8 months (95% CI, 5.6-11.6), and 19.4 months (95% CI, 18.2-NE), respectively.

 helped shed light on real-world data compared with known data from the 2 respective trials, Phull explains. She emphasizes that many patients with relapsed/refractory multiple myeloma in the real-world setting often do not meet the eligibility criteria that are expected for clinical trials. Nevertheless, it’s crucial to compare these data to understand the effect of these CAR T-cell therapies in the real-world setting, Phull concludes.

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Pooja Phull, MD, highlights differences between real-world vs clinical trial data for cilta-cel vs ide-cel in relapsed/refractory multiple myeloma.

Dr Phull on Real-World vs Trial Data for CAR T-Cell Therapy in R/R Multiple Myeloma

“It’s pretty striking that there were significantly lower rates of [cytokine release syndrome (CRS)] on the real-world analysis, as opposed to in the clinical trial outcomes, especially for the cilta-cel group.”

Pooja Phull, MD, hematologist/oncologist, John Theurer Cancer Center, Hackensack University Medical Center, highlights the differences between retrospective real-world and clinical trial data for ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma) in patients with relapsed/refractory multiple myeloma.

, patients with relapsed/refractory multiple myeloma outside of a clinical trial treated with cilta-cel (n = 57) had an overall response rate (ORR) of 86% compared with 60% in those treated with ide-cel (n = 51; 

 = .002). Of note, the progression-free survival (PFS) was not reached (NR) in the cilta-cel group vs 7.5 months in the ide-cel group (

 < .0001); overall survival was NR in both groups (

When comparing these data from the real-world analysis with clinical trial data, a key difference was that there response rates and outcomes were worse in the real-world data, Phull begins, noting that this reflects differences in how patients in the real-world setting receive treatment vs in trial settings where everything is much more controlled, including the patient population enrolled.

Regarding safety, Phull notes that there were significantly lower rates of CRS based on data from the real-world analysis vs clinical trial data, particularly in patients from the cilta-cel group. Within the real-world analysis, data demonstrated that safety profiles were comparable between the cilta-cel and ide-cel groups. Any-grade CRS occurred in 67.2% vs 82.2% of patients in the cilta-cel and ide-cel groups, respectively (

 = .08); grade 3 or greater CRS occurred in 0% vs 2.2% of patients, respectively (

Although there aren’t current data to confirm why CRS rates were lower in the real-world patient population, Phull emphasizes that the majority of patients still experience CRS in the real-world setting. She notes that improvements in bridging therapy could be a factor. Nevertheless, the finding of lower rates of CRS among patients in the real world is reassuring, she concludes.

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“Comparing across trials we see clearly that ciltacabtagene autoleucel seems to have superior response rates as well as more durable responses, and that was also seen in our real-world analysis.” 

Pooja Phull, MD, hematologist/oncologist, John Theurer Cancer Center, Hackensack University Medical Center, discusses findings from a retrospective, real-world analysis comparing the efficacy and safety of ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma) in patients with relapsed/refractory (R/R) multiple myeloma.

The analysis included 114 patients, with 50 receiving ide-cel and 64 receiving cilta-cel. The overall response rate (ORR) was significantly higher with cilta-cel vs ide-cel, at 86% vs 60%, respectively (

 = .002). Additionally, median progression-free survival (PFS) was not reached (NR) with cilta-cel vs 7.5 months with ide-cel (

 < .0001). Overall survival (OS) was NR in either group (

 = .12). Extramedullary disease was associated with worse PFS overall (4.1 vs 21.4 months; 

A univariate analysis confirmed cilta-cel treatment (HR, 0.28; 95% CI, 0.14-0.54; 

 < .001) as favorable and extramedullary disease (HR, 4.3; 95% CI, 2.3-7.9; 

 < .001) as unfavorable prognostic factors.

Safety profiles were comparable. Any-grade cytokine release syndrome (CRS) occurred in 82.2% of ide-cel-treated patients vs 67.2% of cilta-cel-treated patients (

 = .08), with grade 3 or greater CRS occurring in 2.2% and 0% of patients, respectively (

 = .2). Immune effector cell–associated neurotoxicity syndrome (ICANS) was observed in 11.1% of ide-cel-treated patients and 12.1% of cilta-cel-treated patients (

 = .8), with grade 3 or greater ICANS occurring in 2.2% and 3.5%, respectively (

Phull concludes that cilta-cel demonstrated superior ORR and PFS compared with ide-cel, but patient selection influenced outcomes. Ide-cel was frequently chosen for older, frailer patients with greater comorbidities, including higher rates of extramedullary disease.

Pooja Phull, MD, discusses the use of ciltacabtagene autoleucel and idecabtagene vicleucel in R/R multiple myeloma.

Pooja Phull, MD

Articles

Dr Phull on the Rationale for the Retrospective Analysis of CAR T-Cell Therapy in R/R Myeloma

Dr Phull on Real-World vs Trial Data for CAR T-Cell Therapy in R/R Multiple Myeloma

Dr Phull on the Efficacy and Safety of Cilta-Cel vs Ide-Cel in R/R Multiple Myeloma