Consolidation therapy in newly diagnosed adult patients with Ph-negative B-cell ALL

During the ALL Hub Steering Committee meeting, Mark Litzow chaired a discussion on consolidation therapy in newly diagnosed (ND) adult patients with Philadelphia chromosome-negative (Ph−) B-cell acute lymphoblastic leukemia (B-ALL), featuring Oliver Ottmann, Wendy Stock, André Baruchel, Sabina Chiaretti, Nicolas Boissel, José María Ribera, and Charles Mullighan.

Litzow provides an overview of the phase III ECOG-ACRIN E1910 trial (NCT02003222) assessing the safety and efficacy of consolidation chemotherapy with or without blinatumomab in patients aged 30–70 years with ND Ph− B-ALL in measurable residual disease (MRD)-negative remission (Figure 1).

Figure 1. ECOG-ACRIN E1910 study design*

Blin, blinatumomab; chemo, chemotherapy; MRD, measurable residual disease.​
*Adapted from Litzow MR, et al.¹

The primary endpoint was met; after a median follow-up of 43 months, the 3-year OS rate was 85% in the blinatumomab plus chemotherapy arm vs 68% in the chemotherapy alone arm (Figure 2).¹

Figure 2. OS comparison: MRD-negative patients*

Blin, blinatumomab; Chemo, chemotherapy; CI, confidence interval; HR, hazard ratio; MRD, measurable residual disease; NRM, non-relapse mortality; OS, overall survival.
*Adapted from Litzow MR, et al.¹

This survival benefit was also observed in patients aged <55 years (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.05–0.47; p <0.001).¹ The survival benefit of blinatumomab in patients aged ≥55 years did not reach statistical significance (HR, 0.66; 95% CI, 0.33–1.35; p = not significant).¹ The survival benefit was also assessed across risk groups, with a significant improvement in patients with favorable (HR, 0.00; 95% CI, 0.00–not applicable; p = not applicable) and unfavorable (HR, 0.39; 95% CI, 0.19–0.78; p = 0.008) molecular risk.¹ Based on results from this trial, and other trials, the U.S. Food and Drug Administration (FDA) approved blinatumomab as a consolidation therapy for adult and pediatric patients with CD19+ Ph− B-ALL, irrespective of MRD status.²

Discussion

Key discussion points included:

• The panel commented that the use of immunotherapy in earlier lines of treatment could be beneficial and reduce the amount of chemotherapy used.
• The optimal number of cycles of blinatumomab was discussed, and four cycles was recommended as the standard approach.
• MRD analysis in the ECOG-ACRIN E1910 trial was discussed; next-generation sequencing MRD analysis will be carried out to assess the impact of MRD beyond the 10⁻⁴ threshold.
• The impact of age and clinical features on outcomes was highlighted as an area for further exploration.
• Finally, the panel highlighted that full genomic characterization for the ECOG-ACRIN E1910 trial is ongoing.

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