After the results of the phase 2 KarMMa trial showed that idecabtagene vicleucel is a new standard of care in relapsed/refractory multiple myeloma, a real-world analysis continues to show the CAR T-cell therapy could have a wider reach.
Real-world experience with patients with relapsed/refractory multiple myeloma (RRMM) on the standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapy idecabtagene vicleucel (ide-cel; Abecma) showed that patients continued to have a safe and effective response comparable with previous trials, according to results published in the Journal of Clinical Oncology.1
Looking at data retrospectively collected from 11 US institutions, 159 of 196 patients with leukapheresis were given ide-cel by the time of data cutoff on February 28, 2022. Among these patients, researchers saw that after a median follow-up of 6.1 months from CAR T-cell infusion, the median progression-free survival (PFS) was 8.5 months (95% CI, 6.5-not reached [NR]) while the median overall survival (OS) was 12.5 months (95% CI, 11.3-NR).
Further efficacy results remained consistent with the pivotal phase 2 KarMMa trial (NCT03361748) which led to the FDA approval of ide-cel for patients with RRMM2, however, in the real-world analysis, 75% (n = 120) of infused patients observed would not have been eligible to participate in the KarMMA trial due to their comorbidities at the time of leukaphereses.
In the real-world analysis, 90% of eligible patients still received ide-cel, which was comparable with the 91% in KarMMa trial,3 and researchers saw a best overall response rate (ORR) of 84% and a complete response (CR) of 42% in their analysis. In comparison with the trial, this was higher than the ORR of 73% and CR of 33%.
“Our data indicate that CAR T administration in the real world is feasible, safe, and effective, even among patients with comorbidities,” the researchers wrote.
Of the patients observed, the median age was 64-years-old and 35% had high risk cytogenetics. The median number of prior therapies was 7 (range, 4-18) with 44% of patients having penta-refractory disease. In comparison, the median age of patients in the KarMMa trial was 61-years (range, 33-78) with 45% of patients having high-risk cytogenetics. Thirty-three percent of patients in the trial had penta-refractory disease and 39% had extramedullary disease.
Among patients in the analysis who would have not been eligible for the ide-cel treatment in the KarMMa trial, the most common reasons for intelligibly were inadequate organ function in 45 patients (13% had renal dysfunction), prior use of BCMA-TT in 33 patients, cytopenias with an absolute neutrophil count less than 1,000/μL in 22 patients, a hemoglobin level less than 8 g/dL in 25 patients, and a platelet count less than 50,000/μL in 21% of patients. Moreover, researchers observed an ECOG performance score of 2 or higher in 28 patients compared with just 3 patients having a score of 2 on the trial.
Safety in the real-world analysis also remained comparable for this patient population with researchers, noting high amount of cytopenia’s. In just the analysis, they saw a median hospital stay of 9 days (range, 5-69) and that any grade, grade 2 or higher, or grade 3 or higher cytokine release syndrome (CRS) occurred in 82%, 20%, and 3% of patients, respectively. Moreover, neurotoxicity was seen at any grade, grade 2 or more, and grade 3 or more at 18%, 11%, and 6%, respectively. To combat this, most patients received tocilizumab (Actemra), while just 5% received anakinra (Kineret), and 26% received glucocorticoids for CRS, neurotoxicity, or both.
The most common adverse events (AEs) of grade 3 or greater among patients were neutropenia (88%), anemia (51%), and thrombocytopenia (68%). Grade 3 or greater hematologic toxicity that persisted for 30 days or more after infusion included neutropenia (60%), anemia (38%), and thrombocytopenia (59%).
In order to counter these AEs, 74% of patients received granulocyte colony-stimulating factor, 15% received a thrombopoietin agonist, and 5% received an autologous stem-cell boost. Still, infections were seen in 34% of patients, with 20% being bacterial, 16% viral, and 1% were fungal infections.
By the time of follow-up, 30 patients died who had received ide-cel. This included 20 deaths attributed to myeloma progression, 8 due to non-relapse mortality, and in 2 patients, their cause of death was unknown. In patients who died due to non-relapse mortality, 3 patients died due to ide-cel related toxicity, with 2 patients who had grade 5 CRS, with 1 patient who had hemophagocytic lymph-histiocytosis as well concomitant grade 5 CRS, and 1 patient who had neurotoxicity in the form of progressive ascending weakness without evidence of central nervous system myeloma involvement, according to the researchers.
“The manufacturing failure rate in real-world patients is higher than that seen in KarMMa where only 1 of the 140 enrolled patients had a manufacturing failure. Higher rate of manufacturing failure with [standard of care] ide-cel could be due to poor bone marrow reserve among our patients, as reflected by the high rate of baseline cytopenias,” the researchers explained.
With the real-world-data, they were able to look at results and responses to therapy based on factors that may have excluded them from the KarMMa trial. For example, patients not given prior BCMA-TT compared with those given any prior BCMA-TT had an inferior median PFS of 9 vs 3.2 months, respectively (P = .00092). This was also seen with OS results in patients on prior BCMA-TT at a median of 7.4 months compared with a median of 12.5 months for patients without prior BCMA-TT (P = .01). While ineligibility for the KarMMa trial was not included in the multivariable analysis, those infused patients not eligible for the study had a trend toward inferior PFS at a median of 7.6 months compared with 9 months for those who would be eligible (P = .19).
“The efficacy and safety profile with [standard of care] ide-cel is comparable with that observed in the KarMMa trial although the majority of patients would not have met clinical trial eligibility criteria,” the researchers concluded. “It is feasible to administer ide-cel as [standard of care], with high response rates and low incidence of severe CRS and [neurotoxicity], although persistent cytopenias remain an ongoing issue,” concluded the researchers.
1. Hansen D, Sidana S, Peres L, et al. Idecabtagene vicleucel for relapsed/refractory multiple myeloma: real-world experience from the myeloma CAR T consortium. J Clin Oncol. Jan 9:JCO2201365. doi:10.1200/JCO.22.01365
2. U.S. food and drug administration approves Bristol Myers Squibb’s and bluebird bio’s abecma (idecabtagene vicleucel), the first anti-BCMA CAR T cell therapy for relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb. March 26, 2021. Accessed February 3, 2023. https://bit.ly/3m0V915
3. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850