Haematological cancer: Favourable outcomes with CAR T cells

Promising results of clinical trials of CAR-T-cell-based therapies for patients with haematological malignancies have been increasingly reported in the past few years. Two studies presented in the 2017 American Society of Hematology annual meeting and published in the New England Journal of Medicine confirm the favourable outcomes associated with CAR-T-cell therapies in patients with refractory B-cell lymphomas. “Patients with aggressive B-cell non-Hodgkin lymphomas — including diffuse large B-cell lymphoma (DLBL), primary mediastinal B-cell lymphoma, and transformed follicular lymphoma — who are refractory to chemotherapy have an extremely poor prognosis, with a median survival of approximately 6 months. Prior single-institution studies showed that anti-CD19 CAR-T-cell therapy can be very effective in such patients. Therefore, we decided to evaluate the efficacy of axicabtagene ciloleucel (axi-cel) in a multicentre trial,” explains Sattva Neelapu, the main investigator of ZUMA-1. The number of patients enrolled in this phase II trial was 111, of which 77 patients with DLBL and 24 with primary mediastinal B-cell lymphoma or transformed follicular lymphoma received the CAR-T-cell product axi-cel. The second trial involved a smaller cohort of patients, also with non-responsive or chemorefractory disease; of 38 patients enrolled, 14 with follicular lymphoma and 14 with DLBL received CTL019. Empfehlung der Redaktion Jetzt Newsletter bestellen Bleiben Sie up-to-date mit dem Update Onkologie Wir möchten Sie unterstützen, up-to-date zu bleiben, und bieten Ihnen ab sofort „Research Highlights“ aus der internationalen Fachliteratur, ausgewählt und kurz zusammengefasst von unseren Kollegen von Nature Reviews Clinical Oncology. Um sich umfassend über onkologische Themen zu informieren, bestellen Sie unseren interdisziplinären Newsletter Update Onkologie. Both axi-cel and CTL019 have a single-chain variable fragment extracellular domain that targets CD19, and a CD3ζ intracellular domain. One of the main differences in design between these CAR-T-cell products is the intracellular co-stimulatory domain: CD28 in axi-cel, and CD137 in CTL019. All patients enrolled in ZUMA-1 underwent leukapheresis to collect immune cells for the manufacture of axi-cel, which was achieved in all but one patient. “Importantly, the average turnaround time from apheresis to the delivery of axi-cel to the clinical site, 17 days, was short,” highlights Neelapu. In the second study, T-cell manufacturing was unsuccessful for five patients. For patients receiving axi-cel, the objective response and complete response rate at 6 months were 82% and 54%, respectively. At 6 months, the median duration of response was 8.1 months, and at longer follow-up durations (median 15.4 months) it was 11.1 months. Similar outcomes were reported in the second study, with a complete response rate of 57% and a median duration of response of 29.3 months at 6 months. At longer follow-up durations (median 28.6 months), 57% of patients remained free from disease progression. Empfehlung der Redaktion Nature Reviews Clinical Oncology Februar 2018 Dieser Artikel ist erstmals in der Februar-Ausgabe 2018 von Nature Reviews Clinical Oncology erschienen. Weitere Themen sind: Chimeric antigen receptor T-cell therapy — assessment and management of toxicities Chimeric antigen receptor T-cell therapies for lymphoma Among patients receiving axi-cel, 95% had grade ≥3 adverse events. Cytokine release syndrome (CRS) was reported by 93% of patients, including 13% with grade ≥3 CRS. Among patients receiving CTL019, 57% had any-grade CRS, including 18% with grade ≥3 CRS. “The long-term durability observed in ZUMA-1 and in prior single-institution studies with CD19 CAR-T-cell therapy products suggests that this approach could be potentially curative for a significant proportion of these patients,” indicates Neelapu. “The oncology community will probably not be surprised if new CAR T cell therapies are approved in the next few months” The results of ZUMA-1 led to the FDA approval of axi-cel for adult patients with large B-cell lymphomas with no response or disease relapse after at least two lines of therapy. This second approval of a CAR-T-cell-based therapy, on 18 October 2017, occurred less than 2 months after the first of such products was approved. The oncology community will probably not be surprised if new CAR-T-cell therapies are approved in the next few months – whether the success of these therapies is replicated once they become available to all patients who could benefit from them remains to be determined. Dieser Beitrag ist unter dem Originaltitel "Haematological cancer: Favourable outcomes with CAR T cells" erstmals erschienen in Nature Reviews Clinical Oncology 15, 65 (2018), doi.org/10.1038/nrclinonc.2017.208

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Haematological cancer: Favourable outcomes with CAR T cells

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