Safety and efficacy of subcutaneous blinatumomab in adult patients with R/R B-ALL: Phase Ib trial

Novel immunotherapies have improved long-term survival in patients with B-cell acute lymphocytic leukemia (B-ALL). However, outcomes for adult patients with relapsed/refractory (R/R) B-ALL remain poor, and better treatments are warranted. Continuous intravenous infusion of blinatumomab is a standard treatment used in R/R B-ALL. Recently, subcutaneous (SC) delivery of blinatumomab has been developed to further improve efficacy and allow ease of administration for patients.

Here, we summarize results from the dose-expansion phase of a global, single-arm, multicenter phase Ib trial (NCT04521231) investigating the efficacy and safety of single-agent SC blinatumomab in heavily pretreated adult patients with R/R ALL, published by Jabbour et al.¹ in American Journal of Hematology.

Study design¹

• This study included adult patients with R/R ALL who had ≥5% blasts in the bone marrow, and an Eastern Cooperative Oncology Group Performance Status of ≤2.
• Patients received up to five cycles of SC blinatumomab at two doses:
  • 250 μg once daily/500 μg three times weekly; or
  • 500 μg once daily/1000 μg three time weekly.
• The primary endpoint was complete remission/complete remission with partial hematologic recovery (CR/CRh) within the first two cycles.

Key findings¹

• At the data cut off of September 15, 2023, a total of 27 patients with a median age of 52 years (range, 19–78 years) were treated with SC blinatumomab.

Efficacy

• The CR/CRh and measurable residual disease negativity rates at 250 μg/500 μg and 500 μg/1000 μg doses after two cycles are reported in Figure 1.
• Overall, nine patients who achieved measurable residual disease negative CR/CRh after SC blinatumomab underwent allogeneic HSCT
• At the 500 μg/1000 μg dose, one patient developed CD19-negative relapse.

CR, complete remission; CRh, complete remission with partial hematologic recovery; MRD, measurable residual disease
*Data from Jabbour, et al.¹

Safety

The adverse events reported at the 250 μg/500 μg and 500 μg/1000 μg dose are summarized in Table 1. No Grade 4 treatment-related CRS or neurological events were reported.

Table 1. AEs*

AE, adverse event; CRS, cytokine release syndrome; ICANS, immune effector cell associated neurotoxicity syndrome; NE, neurologic event; SC, subcutaneous. *Adapted from Jabbour, et al.1
AEs, %	250 μg/500 μg (n = 14)	500 μg/1000 μg (n = 13)
Any-grade	100	92.3
Related to SC blinatumomab
Serious AEs	64.3	76.9
Fatal AEs	0	0
Grade ≥ 3	85.7	61.5
Treatment discontinuation	14.3	7.7
Treatment interruption	78.6	69.2
Grade ≥ 3 CRS	21.4	23.1
Grade ≥ 3 NE	42.9	23.1
Aphasia	0	7.7
Delirium	0	7.7
Headache	7.1	0
ICANS	21.4	15.4
Neurotoxicity	7.1	7.7
Somnolence	7.1	0
Decrease in platelet count	21.4	23.1
Decrease in white-cell count	0	7.7

Key learnings

Despite the limited sample size, treatment with single-agent SC blinatumomab demonstrated high efficacy and was well-tolerated in heavily pretreated adult patients with R/R B-ALL. These findings have the potential to change practice but require further investigation in randomized controlled trials.