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Dual-targeting CAR T-cell therapy for refractory multiple myeloma

Last updated: 03-06-2020

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Dual-targeting CAR T-cell therapy for refractory multiple myeloma

In this publication, Tang et al. report the efficacy and safety results of 16 patients treated between March 2017 and February 2018 at the First Affiliated Hospital of Soochow University (Suzhou, CN). Patients had received two or more prior therapies without complete recovery, or who had recurrence after recovery (refractory). Median patient age was 55.1 years (range, 50–72).

T-cell collection was undertaken, with cells cultured for 1–2 weeks to generate CAR T cells. Intravenous re-infusion was conducted sequentially after conditioning therapy (100% CD19, 40% BCMA, and 60% BCMA): most patients received fludarabine and cyclophosphamide, but five patients received the infusion immediately following autologous hematopoietic stem cell transplant. The total infused doses ranged between 0.5–1 × 10/kg CD19-targeted CAR T cells and 1.2–6.2 × 10/kg BCMA-targeted CAR T cells. Two patients received 0.5 × 10/kg BCMA CAR T-cell infusion on the surface lesion under B-mode ultrasound guidance.

This study was primarily focused on safety variables, including serum levels of inflammatory factors. All patients experienced cytokine release syndrome (CRS), mainly Grade 1–2 (75.1%), accompanied by a high increase in interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-α, and C-reactive protein, peaking at 3–5 days post-infusion and returning to normal levels by Day 10. Thirteen (81.3%) patients with Grade 2–4 CRS also developed persistent hyperthermia that, in some cases, didn’t reverse until 14 days after infusion. Other frequent adverse events (≥ 50%) were muscle pain (68.8%), headache (56.3%), and nausea (50%).

Regarding efficacy, 14 out of 16 patients treated responded to treatment (overall response rate, 87.5%), with the majority presenting a good response (12 complete responses and two partial responses), comparable to those observed in previous studies (Table 1).

The authors recognize that there is still a need for more significant studies with a higher sample size. Even though all toxicities were managed and patients were stabilized, hospitalization, close monitoring, and symptomatic treatment are still key after CAR T-cell infusion. The efficacy results are encouraging in this difficult-to-treat population, but currently, it’s impossible to confirm the benefit of adding anti-CD19 CAR T cells to anti-BCMA CAR T cells until a comparative, two-arm, randomized study is conducted.

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