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23rd March 2023
Ide-cel therapy for with relapsed and refractory multiple myeloma who had received between two to four previous regimens, significantly prolonged progression-free survival compared to a standard-regimen group, according to a recent and international, open-label, phase 3 trial.
A 2020 study found that the global incidence of multiple myeloma was 160,000 and which led to l106,000 deaths. While autologous stem cell transplantation has been a backbone of therapy for newly diagnosed patients with multiple myeloma eligible for high-dose therapy for decades, nearly all patients will eventually experience disease relapse. Although the introduction of CD38-targeting monoclonal antibodies (MCA), daratumumab and isatuximab, have significantly impacted the management of patients with multiple myeloma, patients who are refractory to CD38 MCA have a poor prognosis. In an earlier, phase 2 trial, ide-cel induced responses in the majority of heavily pre-reated patients with refractory and relapsed multiple myeloma.
In the current study, researchers undertook a phase 3 trial of ide-cel in adults with relapsed and refractory multiple myeloma who had received two to four regimens previously (including immunomodulatory agents, proteasome inhibitors, and daratumumab). Individuals were randomised 2:1 to ide-cel or one of five standard regimens. The primary end point was set as progression-free survival, whereas secondary endpoints included the overall response and survival.
Ide-cel and progression-free survival
A total of 386 patients with a median age of 63 years (60.5% male) underwent randomisation, with 254 assigned to ide-cel and 132 to a standard regimen. A total of 66% of the patients had triple-class-refractory disease, and 95% had daratumumab-refractory disease.
At a median follow-up of 18.6 months, the median progression-free survival was 13.3 months in the ide-cel group, compared to 4.4 months in the standard-regimen group (Hazard ratio, HR for disease progression or death = 0.49, 95% CI 0.38 – 0.65, p < 0.001). A response was seen in a significantly higher proportion of patients who received ide-cel compared to the standard regimen (71% vs 42%, p < 0.001) and a complete response occurred in 39% and 5% respectively. At the time of publication, overall survival data were immature.
Adverse events of grade 3 or 4 occurred more frequently in the ide-cel group (93% vs 75%) and cytokine release syndrome occurred in 88% of the ide-cel group although this was largely of grade 1 or 2 severity. Neurotoxic effects occurred in 15% of the ide-cel group, with 3% having an event of grade 3 or higher.
The authors concluded that ide-cel treatment gave rise to significantly prolonged progression-free survival and an improved response compared with standard regimens in patients with triple-class-exposed relapsed and refractory multiple myeloma.
Rodrigeuz-Otero P et al. Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. N Eng J Med 2023
17th February 2023
In a randomised controlled trial, an international group of researchers showed that the CAR T-cell therapy, Ide-cel (idecabtagene vicleucel) gave rise to greater progression-free survival than any of five other standard regimens in heavily pre-treated patients with relapsed or refractory multiple myeloma.
Although treatments for multiple myeloma have improved in recent years, evidence suggests that around 16% of patients relapse after 8 months of treatment. Nevertheless, while CD38-targeting monoclonal antibodies have made a significant impact to the treatment of patients with multiple myeloma (MM), those who a refractory to this regime have a poor prognosis. The use of CAR T-cell therapies directed against the B-cell maturation antigen (BCMA) expressed on myeloma cells, have proven to be effective in MM. In fact, one Phase II trial in which Ide-cel was given to relapsed or refractory MM patients, generated a response in over 70% of patients, with 33% experiencing a complete response. While CAR T-cell therapy clearly works in relapsed/refractory MM, there is an absence of comparative studies of the treatment compared to other regimes.
In the current study, researchers recruited MM patients who were refractory to between two and four prior regimes. Eligible participants were then randomised 2:1 to Ide-cel or one of five standard regimens and which included immunomodulatory agents, proteasome inhibitors and daratumumab. The primary endpoint was set as progression-free survival whereas secondary endpoints included the overall response and survival.
Ide-cel and progression-free survival
A total of 386 patients with a median age of 63 years (60.5% male) received either Ide-cel (254) or one of the standard regimes. Among the entire cohort, 66% had triple-class refractory disease and 95% daratumumab-refractory disease.
After a median of 18.6 months follow-up, the median progression-free survival in the Ide-cel group was 13.3 months compared to 4.4 months in the standard regime groups (hazard ratio for disease progression or death, HR = 0.49, 95% CI 0.38 – 0.65, p < 0.001). In fact, 12-month progression-free survival was 55% for Ide-cel but only 30% in the standard regimen. Furthermore, a complete response occurred in 39% of the intervention group and on 5% in the standard therapy group. Data on overall survival were immature. In addition, adverse effects of either grade 3 or 4 were more frequent in the Ide-cel group (93% vs 75).
Based on these results, the authors concluded that Ide-cel gave rise to an improved response compared to standard therapy in patients who failed to respond to two to four prior regimens.
Rodriguez-Otero P et al. Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. N Engl J Med 2023