The following article features coverage from the American Society of Hematology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

According to findings presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition held in Orlando, Florida, a response rate of higher than 90% was observed in a phase 1b study of patients with relapsed/refractory multiple myeloma receiving JNJ-4528, a second-generation chimeric antigen receptor T-cell (CAR-T) therapy containing 2 anti–B-cell maturation antigen (BCMA) single-domain antibodies.1

Treatment selection for patients with relapsed/refractory multiple myeloma is associated with many challenges, including more limited treatment options, concerns related to treatment tolerability, and shorter durations of response with each subsequent line of therapy.

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BCMA, a cell-surface protein involved in the regulation of B-cell proliferation, survival, maturation, and differentiation into malignant myeloma cells, represents a selective therapeutic target in multiple myeloma because it is expressed at much higher levels on myeloma cells compared with normal B cells.

The US-based CARTITUDE study (ClinicalTrials.gov Identifier: NCT03548207) is an ongoing open-label, single-arm, phase 1/2 clinical trial investigating the safety and efficacy of JNJ-4528 in adult patients with relapsed/refractory multiple myeloma.


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Results of the dose-finding, phase 1b portion of the study, with primary objectives of safety and confirmation of the recommended phase 2 dose of 0.75 x 106 CAR-T cells/kg from the LEGEND-2 clinical trial (ClinicalTrials.gov Identifier: NCT03090659), are presented here.

Previous reports from LEGEND-2, a first-in-human, phase 1/2 study of the same CAR construct, showed promising results, including a high response rate and a manageable safety profile.2

Of the 29 patients treated with JNJ-4528 in the phase Ib portion of the CARTITUDE study, the median patient age was 60 years, the median number of prior lines of therapy was 5, and 86% had disease that was refractory to a proteasome inhibitor, a immunomodulatory drug, and an anti-CD38 antibody. The median dose of JNJ-4528 included 0.73 x 106 CAR-T cells/kg – very close to the target dose of 0.75 x 10-6 CAR-T cells/kg.

Regarding the safety of JNJ-4528, 93% of patients experienced cytokine release syndrome (CRS), although almost all of these events were classified as grade 1/2. However, 1 grade 3 and 1 grade 5 CRS-related event occurred.

CRS had a median onset of 7 days following infusion of JNJ-4528, and a median duration of 4 days. Of patients experiencing CRS, tocilizumab and corticosteroids were administered to 76% and 21%, respectively. Three patients experienced CRS-related neurotoxicity consistent with immune effector cell-associated neurotoxicity syndrome (ICANS) (grade 3 [1 individual]), which resolved within 1 day after administration of tocilizumab/corticosteroids..

Grade 3 or higher neutropenia, thrombocytopenia, and anemia occurred in 93%, 69%, and 55% of patients, respectively.

Of the 29 patients evaluable for response, the overall response rate was 100%, with rates of stringent complete response, complete response, very good partial response, and partial response of 66%, 3%, 17%, and 14%, respectively. Median time to first response and median time to CR were 1 month.

Furthermore, of the 17 patients who were evaluable for an assessment of minimal residual disease (MRD), 9 were classified as minimal residual disease (MRD)-negative at the 10-6 level, 5 were classified as MRD-negative at the level of 10-5, and 3 were MRD-negative at the 10-4 level.

At a median follow-up of 6 months, 27 of the 29 patients have not experienced disease progression.

CAR-T cell expansion and persistence were observed in all patients, with CAR-T cells peaking at a median of 10 to 14 days postinfusion, with CRS typically manifesting 2 days prior to CAR-T cell peak.

In her concluding remarks, Deepu Madduri, MD, of the Icahn School of Medicine at Mount Sinai in NYC, the presenting study author, commented that “the safety and efficacy results from the CARTITUDE-1 study appear consistent with the LEGEND-2 study.”

Dr Madduri also noted that the US Food and Drug Administration has recently granted JNJ-4528 a breakthrough therapy designation.3

Disclosure: The clinical trial described in this presentation was sponsored by Janssen Research & Development, LLC. For a full list of disclosures, please refer to the original abstract.

Read more of Cancer Therapy Advisor‘s coverage of ASH’s annual meeting by visiting the conference page.

References

  1. Madduri D, Usmani SZ, Jagannath S, et al. A phase Ib/2 study of JNJ-4528, a CAR-T cell therapy directed against B-cell maturation antigen (BCMA), in patients with relapsed and/or refractory multiple myeloma (R/R MM). Presented at: 61st American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 577.
  2. Zhao WH, Liu J, Wang BY, et al. A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. J Hematol Oncol. 2018;11:141.
  3. Janssen. 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 December 9, 2019.