Relapsed/refractory patients

The U.S. FDA grants JNJ 4528 breakthrough therapy designation

On 6th December 2019, the United States (U.S.) Food & Drug Administration (FDA) announced it had granted breakthrough therapy designation to JNJ 4528 for the treatment of relapsed/refractory multiple myeloma (RRMM). JNJ 4528 is anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy. This approval was based on results from the LEGEND-2 and CARTITUDE-1 trials. JNJ 4528 was previously granted orphan drug designation by the U.S. FDA in February 2019, and PRIME designation by the European Medicines Agency (EMA) in April 2019.1


JNJ 4528, known as LCAR-B38M in China, was first investigated in the phase I LEGEND-2 trial. In December 2018, the results of this trial were published in the Journal of Hematology & Oncology. This analysis reported the outcomes of 57 patients with RRMM who had received a median of three prior lines of therapy. Efficacy was promising with 88% of patients achieving an overall response; 68% complete response (CR), 5% very good partial response (VGPR), and 14% partial response (PR). Additionally, 63% of patients achieved minimal residual disease (MRD)-negative disease.2 Read more about the results from LEGEND-2 on the Multiple Myeloma (MM) Hub here.

In China, the phase II CARTIFAN-1 study (NCT03758417) is ongoing to further evaluate the efficacy of LCAR-B38M in patients with RRMM.1 Additionally, data from LEGEND-2 with a longer follow-up is due to be presented at the 61st American Society of Hematology (ASH) meeting (abstract #579) in December.3


The phase Ib/II CARTITUDE-1 (NCT03548207) trial is investigating JNJ 4528 in patients with RRMM in the US.3

Study design3

  • Patients with RRMM who have received three or more prior lines of therapy or are double refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), have received a PI, IMiD and anti-CD38 antibody, and who progressed within 12 months of their last line of therapy
  • The safety and dose was informed by the phase I LEGEND-2 trial
  • Primary objective of phase II portion: evaluate efficacy
    • Primary endpoint: overall response rate (ORR)

Patient characteristics3

  • Patients with RRMM, n=29
  • Median patient age: 60 years (50 –75)
  • Median prior lines of therapy: 5 (3–18)
  • Median administered dose: 0.73 x 106 CAR T cells/kg
  • 86% of patients were triple-refractory to a PI, IMiD and anti-CD38 antibody
    • 72% were penta-exposed
    • 31% were penta-refractory

Efficacy3 at data cut-off of 6th November 2019

  • ORR: 100%
    • ≥ CR: 69%
      • Stringent CR (sCR): 66%
      • 100% of patients achieving CR were MRD-negative at 10-5
    • ≥ VGPR: 17%
    • PR: 14%
  • Median follow-up of six months: 27/29 were progression-free


  • Most common adverse events:
    • Cytokine release syndrome : 93%
      • Grade I-II: 80%
      • One grade III event
      • One grade V event
      • Median time to onset: seven days
    • Neutropenia: 93%
    • Thrombocytopenia: 86%
    • Anemia: 86%

The results of this study are due to be presented at the 61st ASH meeting on Monday 9th December 2019 (abstract #577). The MM Hub will be covering the LEGEND-2 and CARTITUDE-1 sessions via social media and as written articles following the 61st ASH meeting. Additionally, we will be publishing an interview with Deepu Madduri who spoke to us about the CARTITUDE-1 trial results.3

  1. PR Newswire. Janssen Announces BCMA CAR-T Therapy JNJ-4528 Granted U.S. FDA Breakthrough Therapy Designation for the Treatment of Relapsed or Refractory Multiple Myeloma. Published; December 6 2019, [Accessed 2019 Dec 07]
  2. Zhao W. H. et al., A phase I, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapse or refractory multiple myeloma. J Hematol Oncol. 2018 Dec 20; 11:141.DOI: 10.1186/s13045-018-0681-6.
  3. LEGEND Biotech. Initial Data from Phase 1b/2 Study of BCMA-Directed CAR-T Cell Therapy JNJ-4528 Show Early and High Responses in Advanced Relapsed or Refractory Multiple Myeloma. Published; December 7 2019, [Accessed 2019 Dec 07]
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