Dataset Information

A phase 2a, single-arm, open-label study of tafasitamab, a humanized, Fc-modified, anti-CD19 antibody, in patients with relapsed/refractory B-precursor cell acute lymphoblastic leukemia.

ABSTRACT:

Background

B-precursor cell acute lymphoblastic leukemia (B-ALL) in adults is an aggressive and challenging condition, and patients with relapsed/refractory (R/R) disease after allogeneic stem cell transplantation (SCT), or noncandidates for SCT, have a particularly poor prognosis. The authors investigated the activity of the Fc-modified anti-CD19 antibody tafasitamab in adults with R/R B-ALL (NCT01685021).

Methods

Adults with R/R B-ALL received single-agent tafasitamab 12 mg/kg weekly for up to four 28-day cycles. Patients with complete remission (with or without neutrophil/platelet recovery; complete remission [CR] or complete remission with incomplete count recovery [CRi]) after cycles 2, 3, or 4 could continue tafasitamab every 2 weeks for up to 3 further months. The primary end point was overall response rate (ORR).

Results

Twenty-two patients were treated (median, 2 prior lines of therapy; range, 1-8). Six patients completed 2 cycles, and 2 of these patients responded for an ORR of 9%; 16 patients (73%) progressed before their first response assessment. Responses lasted 8 and 4 weeks in the 2 patients with CR and minimal residual disease (MRD)-negative CRi, respectively. Tafasitamab produced rapid B-cell/blast depletion in 21 of 22 patients within 1 to 2 weeks of first administration. Tafasitamab was well tolerated, with the most frequent adverse events being infusion-related reactions (59.1%) and fatigue (40.9%). Grade 3 to 4 febrile neutropenia (22.7%) was the most common hematologic adverse event.

Conclusions

Tafasitamab monotherapy was associated with clinical activity in a subset of patients with R/R B-ALL, including short-lasting CR and MRD-negative CRi. Given its favorable tolerability profile, further development of tafasitamab in chemoimmunotherapy combinations and MRD settings should be explored.

SUBMITTER: Klisovic RB

PROVIDER: S-EPMC9292493 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

A phase 2a, single-arm, open-label study of tafasitamab, a humanized, Fc-modified, anti-CD19 antibody, in patients with relapsed/refractory B-precursor cell acute lymphoblastic leukemia.

Klisovic Rebecca B RB Leung Wing H WH Brugger Wolfram W Dirnberger-Hertweck Maren M Winderlich Mark M Ambarkhane Sumeet V SV Jabbour Elias J EJ

Cancer 20210803 22

<h4>Background</h4>B-precursor cell acute lymphoblastic leukemia (B-ALL) in adults is an aggressive and challenging condition, and patients with relapsed/refractory (R/R) disease after allogeneic stem cell transplantation (SCT), or noncandidates for SCT, have a particularly poor prognosis. The authors investigated the activity of the Fc-modified anti-CD19 antibody tafasitamab in adults with R/R B-ALL (NCT01685021).<h4>Methods</h4>Adults with R/R B-ALL received single-agent tafasitamab 12 mg/kg w ...[more]

PMID: 34343354

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Project description:BackgroundFor CD19-positive relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) after treatment with murine CD19 (mCD19) CAR-T, the reinfusion of mCD19 CAR-T cells may be ineffective due to anti-mouse single-chain variable fragment (scFv) antibody caused by mCD19 CAR. To overcome this immunogenicity, we applied humanized CD19 (hCD19) CAR-T cells to treat r/r B-ALL patients with prior mCD19 CAR-T therapy.MethodsNineteen pediatric and adult patients were included, 16 relapsed after and 3 were primarily resistant to mCD19 CAR-T. All patients presented with more than 5% blasts in bone marrow and/or extramedullary disease, and still showed CD19 antigen expression. Humanized CD19-CARs were lentiviral vectors carrying a second generation CAR with 4-1-BB co-stimulatory and CD3ζ signaling domains. Patient-derived cells were collected for producing CAR-T cells, the median dose of infused hCD19 CAR-T cells was 2.4 × 105/kg (range, 1.0-18.0 × 105/kg).ResultshCD19 CAR-T resulted in a complete remission (CR) rate of 68% (13/19). Among 13 remission patients, 11 underwent allogeneic hematopoietic cell transplantation (allo-HCT) (3 were second HCT) and 10 remained in CR; the event-free survival rates at 12-18 months were 91% in 11 patients received following allo-HCT and 69% in all CR patients. Six cases had no response to hCD19 CAR-T, 3 died of disease progression; another 3 received salvage second transplantation, of them, 2 relapsed again (one died). Cytokine release syndrome (CRS) occurred in 95% (18/19) of patients, most CRS events were grade 1 and grade 2 (n = 17), there was only one grade 4 CRS. Two cases experienced grade 1 neurotoxicity.ConclusionsHumanized CD19 CAR-T cell therapy could be a treatment option for CD19-positive B-ALL patients who relapsed after or resisted prior murine CD19 CAR-T, hCD19 CAR-T followed by allo-HCT provided a longer remission in CR patients. Nevertheless, the prognosis of non-responders to hCD19 CAR-T remained dismal.Trial registrationChinese Clinical Trial Registry/WHO International Clinical Trial Registry ( ChiCTR1900024456 , URL: www.chictr.org.cn ); registered on July 12, 2019.

Dataset Information

A phase 2a, single-arm, open-label study of tafasitamab, a humanized, Fc-modified, anti-CD19 antibody, in patients with relapsed/refractory B-precursor cell acute lymphoblastic leukemia.

Background

Methods

Results

Conclusions

Publications

A phase 2a, single-arm, open-label study of tafasitamab, a humanized, Fc-modified, anti-CD19 antibody, in patients with relapsed/refractory B-precursor cell acute lymphoblastic leukemia.

Similar Datasets

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