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.

Keywords: B-lymphocytes; CD19; MOR208; Xmab5574; acute lymphoblastic leukemia; antineoplastic monoclonal antibody.

Conflict of interest statement

Rebecca B. Klisovic reports support from Incyte and MorphoSys AG during the conduct of the study and support for attending meetings from Novartis and participation on a data safety monitoring board or advisory board for Incyte outside the submitted work. Wolfram Brugger is an employee of MorphoSys AG and has stock or stock options in AstraZeneca. Maren Dirnberger‐Hertweck is an employee of MorphoSys AG. Mark Winderlich is an employee of MorphoSys AG. Sumeet V. Ambarkhane is an employee of MorphoSys AG. Elias J. Jabbour reports research grants and consulting fees from AbbVie, Amgen, Adaptive Biotechnology, BMS, Pfizer, Takeda, Genentech, Incyte, and MorphoSys AG. Wing H. Leung has nothing to disclose.

© 2021 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.

Figures

Figure 1

Treatment algorithm. CR indicates complete remission; CRi, complete remission with incomplete count recovery; EOS, end of study; PD, progressive disease; PR, partial remission.

Figure 2

Time on study for responders. CRi indicates complete remission with incomplete count recovery.

Figure 3

Peripheral B‐cell/lymphoblast counts. C, cycle; D, day.

Figure 4

(A) Baseline CD19/CD20 expression levels per B lymphoblas, and (B) frequency of CD19/20‐positive cells among peripheral B lymphoblasts. The median CD20 expression is 4885 molecules per cell, and the median CD19 level is 17,878 molecules (not plotted). The black triangle shows 25,763 CD20 molecules and 18,257 CD19 molecules (n = 13 patients) on the B lymphoblast surface.