Sequential therapy with inotuzumab ozogamicin, CD19 CAR T cells, and blinatumomab in an elderly patient with relapsed ac
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LETTER TO THE EDITOR
Sequential therapy with inotuzumab ozogamicin, CD19 CAR T cells, and blinatumomab in an elderly patient with relapsed acute lymphoblastic leukemia Ramona Wullenkord 1 & Christian Reicherts 1 & Jan-Henrik Mikesch 1 & Julia Marx 1 & Klaus Wethmar 1 & Jörn Albring 1 & Simon Call 1 & Georg Lenz 1 & Matthias Stelljes 1 Received: 29 June 2020 / Accepted: 18 August 2020 # The Author(s) 2020
Dear Editor, Whereas outcome in younger patients with acute Blymphoblastic leukemia (B-ALL) improved over the last decades, prognosis for older patients, especially with relapsed or refractory (r/r) disease, remains particularly dismal [1, 2]. Novel targeted approaches including inotuzumab ozogamicin (InO), blinatumomab (Blina), and CD19-directed chimeric antigen receptor (CAR) T cells demonstrated promising efficacy in recent phase II/III trials [3–9]. Here, we report a case of an elderly patient with repeatedly relapsed ALL treated sequentially with InO, CD19-specific CAR T cells, and finally, with Blina for relapse after CAR T cell therapy. In March 2017, a 73-year-old female patient was diagnosed with a precursor B-ALL. Flow cytometry showed 95% positivity for CD19 and CD22 surface antigens. First complete remission with no detection of minimal residual disease (MRD) was achieved after a first cycle of standard induction chemotherapy. After six additional cycles of chemotherapy, a molecular relapse occurred followed by an overt relapse in June 2018. The patient was treated with six cycles of InO, inducing a MRD-negative CR without relevant adverse events or alterations in quality of daily life. In March 2019, a second relapse occurred. Lymphocytes were harvested for autologous CAR T cell production within a clinical trial (NCT03853616). While waiting for the CAR T cell product, the patient progressed with symptomatic CNS involvement. Hence, further treatment continued off study and consisted of intrathecal chemotherapy and a further cycle of InO. Subsequently, a partial remission with no evidence of active CNS involvement could be achieved. After a lymphodepleting chemotherapy, * Matthias Stelljes [email protected] 1
Department of Medicine A, Hematology and Oncology, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany
the patient received CD19 CAR T cells without any complications or any impairment in quality of life. CAR T cell persistence in the peripheral blood was measurable until day 20 (Fig. 1). Remission control showed a third MRD-negative remission. Five months after CAR T cell therapy, MRD turned positive again, followed by a third overt relapse with involvement of bone marrow and CNS in December 2019. After clearance of blasts in the cerebrospinal fluid by intrathecal chemotherapy, the patient received Blina and achieved a fourth MRD-negative CR after the first cycle. Except mild neurological adverse reactions, treatment was well tolerated and continued for two additional cycles. Treatment of r/r B-ALL in older patients remains a clinical challenge and is often
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