A phase I study of anti‐BCMA CAR T cell therapy in relapsed/refractory multiple myeloma and plasma cell leukemia

Abstract

Background Relapsed/refractory (R/R) multiple myeloma (MM) patients and primary plasma cell leukemia (PCL) have an unfavorable prognosis and no effective treatment. This study was designed to assess the safety and preliminary efficacy of a novel anti‐B‐cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell in R/R MM and PCL. Methods Between February 22, 2017, and June 25, 2018, 28 R/R and two R/R primary PCL patients received a median dose of 11.2 × 10 6 CAR+ cells/kg. The subjects were refractory to a proteasome inhibitor and/or an immunomodulatory agent. Fludarabine and cyclophosphamide were given as lymphodepletion chemotherapy. Results Results for these 30 consecutive patients who received an anti‐BCMA CAR T cell infusion are reported. The patients had received a median of four prior lines of therapy. A total of 44 different types of adverse events were recorded, and hematologic toxic effects were the most common events of any grade during treatment. Hematologic toxic effects were also the most common events of grade 3 or higher. A total of 29 patients (96.7%) had cytokine release syndrome, which was of grade 1 or 2 in 24 patients (80%) and grade 3 in five patients (16.7%). Neurologic toxic effects only occurred in one patient (3.3%) and were of grade 1. The objective response rate was 90%, and the complete response rate was 43.3%. With a median follow‐up of 12.6 months, the median progression‐free survival (PFS) and overall survival were 5.2 months and 14.0 months. One of the two primary PCL achieved a complete response with a PFS of 307 days. The other patients achieved a very good partial response with a PFS of 117 days. Conclusions Anti‐BCMA CAR T cell treatment is safe and highly active in R/R multiple myeloma.

Risk Factors Associated with Durable Progression-Free Survival in Patients with Relapsed or Refractory Multiple Myeloma Treated with Anti-BCMA CAR T-cell Therapy

“…(17) Zhou et al reported that treatment with more than six treatment lines was a significant predictor of a VGPR or better response and suggested that earlier CAR-T cell therapy may infer additional benefits to the patients. (19) Although the present study failed to detect a significant association, exposure to three prior treatment lines was an independent predictive factor for PFS. These findings support the theory that earlier CAR-T therapy may be more beneficial to patients.…”

“…(18) Another trial involving 28 R/R MM and two primary plasma cell leukemia (PCL) patients indicated that those who received previous ASCT treatment or had extramedullary disease/PCL had a poor prognosis. (19) The outcomes following prior ASCT were inconsistent between the two studies; however, the present analyses failed to detect an association between prior ASCT and the prognosis of MM patients receiving anti-BCMA CAR-T cell therapy. A significant association was also found between extramedullary disease and poor prognosis; however, it was an independent predictor of disease progression in patients who received CAR-T therapy and of relapse among patients who achieved CR.…”

“…(14)(15)(16) Recently, some multiple clinical trials have reported encouraging ORR rates ranging from 73-100% and CR rates ranging from 33-76.5% for R/R MM receiving anti-BCMA CAR-T cell therapy. (16)(17)(18)(19)(20) Despite encouraging results from trials investigating anti-BCMA CAR-T cell therapy for R/R MM, some unresolved issues remain. For example, the ORR and CR rate, as well as therapy-associated complications, have varied widely among clinical trials, with a subset of patients experiencing relapse following anti-BCMA CAR-T treatment.…”

Anti-BCMA CAR-T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease: A Single Center Analysis of Two Clinical Trials

“…Anti-BCMA CAR-T therapy achieved the most prominent responses in RRMM, with a high objective response rate (ORR) (11)(12)(13)(14)(15)(16)(17). We reviewed the published clinical trials with raw data available and found that several of these studies have enrolled EMM patients, but no analysis was performed on this specific subgroup (10,17).Therefore, we firstly reported the differences in clinical response, adverse events, and pharmacokinetics between EMM and non-EMM patients receiving anti-BCMA CAR-T cell therapy in our center.…”

Viral infection/reactivation during long-term follow-up in multiple myeloma patients with anti-BCMA CAR therapy

“…Participants were patients from two different anti-BCMA CAR T-cell trials, registered on Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) with registry numbers ChiCTR-OPC-16009113 and ChiCTR1800018137, for murine- and fully human-originate CAR, respectively. Four patients participated in both trials and were identified as independent subjects in either trial [ 4 , 5 ]. Patients who died or lost to follow-up within 1 month post infusion were excluded (Fig.…”