Study E1910

The efficacy of BLINCYTO was evaluated in a randomized, controlled study in adult patients with newly diagnosed Philadelphia chromosome-negative B-cell precursor ALL (Study E1910) [NCT02003222]. Eligible patients in hematologic complete remission (CR) or CR with incomplete peripheral blood count recovery (CRi) following induction and intensification chemotherapy were randomized 1:1 to receive a consolidation regimen comprised of multiple cycles of BLINCYTO monotherapy in addition to multiple cycles of intensive chemotherapy (BLINCYTO arm) or to intensive chemotherapy alone (chemotherapy arm). Randomization was stratified by age (< 55 years versus ≥ 55 years), CD20 status, rituximab use, and intent to undergo allogeneic stem cell transplantation (HSCT).

The postremission treatment consisted of a BFM-like chemotherapy regimen adapted from the E2993/UKALLXII clinical trial. Patients randomized to the BLINCYTO arm were to receive 2 cycles of BLINCYTO followed by 3 cycles of consolidation chemotherapy, then a third cycle of BLINCYTO followed by the fourth cycle of chemotherapy and a fourth cycle of BLINCYTO (total 8 cycles). BLINCYTO was administered as a continuous intravenous infusion at 28 mcg/day on Days 1-28. Patients randomized to the chemotherapy arm of the study were to receive 4 cycles of chemotherapy alone (total 4 cycles). Patients on the BLINCYTO arm could go to HSCT after 1 - 2 cycles of BLINCYTO and up to 2 cycles of consolidation chemotherapy, and patients randomized to the chemotherapy arm could go to HSCT after intensification and up to 3 cycles of consolidation chemotherapy. All patients who completed consolidation but did not go to HSCT received maintenance therapy through 2 1/2 years from the start of intensification.

The demographics and baseline characteristics are provided in Table 22.

Efficacy was established on the basis of overall survival (OS). The results with a median follow-up of 3.6 years are shown in Figure 2 and Table 23.

In a later analysis with a median follow-up of 4.5 years, the 5-year OS was 82.4 % [95% CI (73.7, 88.4)] in the BLINCYTO + chemotherapy arm and 62.5 % [95% CI (52.0, 71.3)] in the chemotherapy arm. The hazard ratio was 0.44 [95% CI (0.25, 0.76)].

Study 20120215

The efficacy of BLINCYTO compared to consolidation chemotherapy was evaluated in a randomized, controlled, open-label, multicenter study (Study 20120215) [NCT02393859]. Eligible patients were 28 days to 18 years old and had high-risk, first-relapsed, Philadelphia chromosome-negative B-cell precursor ALL with < 25% blasts in the bone marrow after induction and 2 cycles of consolidation chemotherapy. Patients were randomized 1:1 to receive BLINCYTO or the IntReALLHR2010 HC3 intensive combination chemotherapy as the third cycle of consolidation. Patients in the BLINCYTO arm received one cycle of BLINCYTO as a continuous intravenous infusion at 15 mcg/m2/day over 4 weeks (maximum daily dose was not to exceed 28 mcg/day). Randomization was stratified by age, minimal residual disease status determined at the end of induction based on local assessment, and bone marrow status determined at the end of the second block of consolidation chemotherapy. Patients were to proceed to HSCT after this cycle of consolidation.

There were 54 patients randomized to the BLINCYTO arm and 57 to the chemotherapy arm. The demographics and baseline characteristics are shown in Table 24.

Efficacy was established on the basis of overall survival (OS) and relapse-free survival (RFS). See Table 25, Figure 3, and Figure 4 for results of OS and RFS from Study 20120215.

The median follow-up time for OS was 55.2 months for the overall population. Figure 3 presents a Kaplan-Meier plot comparing OS between treatment arms for the overall population.