CAR T-cell therapy could ‘revolutionize’ treatment of advanced multiple myeloma
JNJ-4528, a chimeric antigen receptor T-cell therapy, induced early, deep and durable responses among patients with relapsed or refractory multiple myeloma, according to study results presented during the ASCO20 Virtual Scientific Program.
In addition, the low rate of high-grade cytokine release syndrome (CRS) observed in the phase 1b/phase 2 CARTITUDE-1 study could encourage use of this investigational autologous cell therapy in an outpatient setting, according to the researchers.
JNJ-4528 (Janssen Pharmaceuticals) is a CAR T-cell therapy that targets the B-cell maturation antigen. Interim results of CARTITUDE-1, based on median follow-up of 6 months, were presented at last year’s ASH Annual Meeting and Exposition.
The updated results presented at ASCO showed JNJ-4528 continued to be associated with deep and sustained responses among patients with advanced multiple myeloma.
“The results are pretty impressive,” Jesus G. Berdeja, MD, director of myeloma research at the Sarah Cannon Research Institute, told Healio.
“These results are strong enough that they make JNJ-4528 a very strong candidate to be one of the first BCMA-directed CAR-T products approved by the FDA for multiple myeloma,” Berdeja said. “I think it will eventually revolutionize the treatment of patients with relapsed or refractory disease.”
The FDA granted breakthrough therapy designation to JNJ-4528 in December for the treatment of adults with relapsed or refractory multiple myeloma who received at least three prior lines of therapy.
The CARTITUDE-1 trial included 29 adults (median age, 60 years; range, 50-75; 52% women) with multiple myeloma per International Myeloma Working Group criteria. All patients had received at least three previous lines of therapy (median, 5; range, 3-18), and 25 (86%) were triple-refractory to a proteasome inhibitor, immunomodulatory drug and anti-CD38 antibody.
Twenty-eight patients (97%) were refractory to their last line of therapy.
Patients received a single IV infusion of JNJ-4528 (median, 0.73 × 106 CAR T cells/kg) 5 to 7 days after a 3-day lymphodepletion chemotherapy regimen with 300 mg/m2 cyclophosphamide plus 30 mg/m2 fludarabine.
Updated results, with median follow-up of 11.5 months (range, 3-17), showed an overall response rate of 100%. Twenty-five patients (86%) had stringent complete responses, three patients had very good partial responses and one patient had a partial response to therapy.
Median time to complete response was 3 months (range, 1-13). Twenty-two of the 29 patients remained progression-free, with a 9-month PFS rate of 86% (95% CI, 67-95). The longest ongoing response exceeded 15 months.
The results compare favorably with those of FDA-approved therapies, which confer response rates of 20% to 30% and PFS of about 4 months for this population with multiple myeloma, according to Berdeja.
“The reason there is so much excitement around CAR-T therapies is that we are seeing response rates that are similar to front-line therapies, but the question remains as to how durable these responses will be,” he said. These updated data from CARTITUDE-1 provide further evidence of the durability of responses seen with the CAR construct used in JNJ-4528, Berdeja added.
The study’s safety results showed 93% of patients had some form of CRS but only two patients had grade 3 or greater CRS. Only three patients experienced neurotoxicity consistent with immune effector cell-associated neurotoxicity syndrome, including one grade 3 or greater case.
Median time to onset of CRS was 7 days (range, 2-12), with a median duration of 4 days (range, 2-64).
One patient died of CRS and another died of acute myeloid leukemia not related to study treatment.
Hematologic adverse events included grade 3 or greater neutropenia, experienced by all 29 patients, and thrombocytopenia, which occurred among 86% of patients. Twenty patients (69%) experienced grade 3 or greater thrombocytopenia.
Compared with many other BCMA-directed CAR T-cell therapies, CRS developed more slowly with JNJ-4528, Berdeja said. Patients treated with typical CAR-T products show symptoms of CRS within a day or two of infusion, he added.
Because of the longer median time to CRS symptoms seen in this study, Berjeda said there is a possibility that this therapy could be given in an outpatient setting, and that only those patients who progress to show symptoms of CRS would need to be hospitalized for post-infusion observation and treatment.
“This could possibly make the treatment more widely accessible for patients and clinicians,” he said.
“The development of CAR-T products will eventually change how we treat myeloma, and I believe that these highly effective treatments will supplant some of the continuous therapies that we are currently giving to our patients,” Berdeja said. “The hope is that someday these will become curative therapies.”
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Berdeja JG, et al. Abstract 8505. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.