Real-World Study Confirms Blinatumomab Effectiveness as Bridge to Transplant in B-Cell Precursor ALL
核心洞察
A large European real-world study of 264 adults treated with blinatumomab found high complete remission rates of 82.0% in relapsed/refractory BCP-ALL and 81.8% MRD response in MRD-positive patients.
Earlier blinatumomab use was associated with improved survival outcomes, with median OS of 31.7 months in first salvage versus 13.0 months in later salvage therapy.
Over 60% of responding patients proceeded to allogeneic stem cell transplantation, with most not requiring additional anti-cancer therapy beforehand.
A large, multicenter real-world study has confirmed that blinatumomab, a CD19 (搜索)/CD3 (搜索)-bispecific T-cell engager, delivers high rates of hematologic remission and measurable residual disease (MRD) response in adult patients with Philadelphia chromosome–negative (Ph−) B-cell precursor acute lymphoblastic leukaemia (搜索) (BCP-ALL) treated in routine clinical practice across Europe.
The post-authorisation safety study (PASS; NCT03117621), published in a correspondence to the editor, evaluated 264 adult patients treated with blinatumomab between 2015 and 2022 across 78 centres in 13 European countries. This represents the largest reported real-world study of blinatumomab-treated patients to date.
High Response Rates Across Disease Settings
Of 246 patients with Ph− BCP-ALL included in the effectiveness analysis, 46 had MRD-positive (MRD+) disease and 183 had relapsed/refractory (R/R) disease, including 60 patients in the clinically important late first relapse (LFR) subgroup, defined as initial remission lasting 12 months or longer.
In the MRD+ group, 27 of 33 evaluable patients (81.8%) achieved an MRD response, with similar rates observed across patients in first remission (CR1) and subsequent remission (CR2+). Median disease-free survival was 31.2 months (95% CI, 5.9–not estimable), and overall survival was not reached after a median follow-up of 44.6 months. The 24-month OS was 67% (95% CI, 51–79) overall, with more favorable outcomes for patients in CR1 (82%) compared with CR2+ (62%).
In the R/R group, 150 patients (82.0%) achieved complete remission (CR), CR with partial hematologic recovery (CRh), or CR with incomplete hematologic recovery (CRi), including 124 patients (82.7%) achieving CR. Among 126 MRD-evaluable patients, 95 (75.4%) achieved an MRD response. Both CR/CRh/CRi and MRD response rates were higher in patients receiving blinatumomab as first salvage therapy (S1) compared with later salvage (S2+).
Earlier Use Drives Better Survival
The study demonstrated a clear association between earlier blinatumomab administration and improved survival outcomes. In the R/R group, median relapse-free survival (RFS) was 15.9 months (95% CI, 8.7–41.3) and overall survival was 29.9 months (95% CI, 17.8–not estimable). Patients receiving blinatumomab as first salvage had longer RFS (16.0 months vs 8.7 months) and OS (31.7 months vs 13.0 months) compared with those receiving later salvage therapy.
MRD responders had substantially longer median RFS than non-responders (20.5 months vs 6.5 months), reinforcing the prognostic importance of achieving an MRD response. The 24-month OS was 52% (95% CI, 44–59) overall and reached 71% (95% CI, 58–81) among LFR patients.
Patients with prior allogeneic haematopoietic stem cell transplantation (allo-HSCT) showed a trend toward better CR/CRh/CRi response (89.5%) compared with those without prior transplant (80.0%), and prior allo-HSCT was associated with substantially prolonged OS (74.7 months vs 22.6 months). The authors note this may reflect enhanced blinatumomab activity facilitated by donor-derived T-cells.
Effective Bridge to Transplant
Following blinatumomab treatment, a substantial proportion of patients proceeded to allo-HSCT: 33 of 46 MRD+ patients (71.7%) and 92 of 150 R/R patients in CR/CRh/CRi (61.3%). Notably, most patients did not require additional anti-cancer therapy prior to transplant (84.8% in MRD+ and 69.6% in R/R), highlighting blinatumomab's role as an effective bridge to transplant.
Consistent Safety Profile
In the full safety analysis set (N=264), treatment-related treatment-emergent adverse events (TR-TEAEs) occurred in 182 patients (68.9%). Grade ≥3 TR-TEAEs were reported in 91 patients (34.5%), serious TR-TEAEs in 77 patients (29.2%), and fatal TR-TEAEs in two patients (respiratory failure secondary to cytokine release syndrome and neurotoxicity).
The most common TR-TEAEs were pyrexia (27.7%), cytokine release syndrome (14.4%), and headache (11.4%). Among TR-TEAEs of special interest, neurologic events occurred in 28.0% (grade ≥3, 8.0%), CRS in 14.4% (grade ≥3, 3.8%), and opportunistic infections in 1.5% (grade ≥3, 0.4%). Blinatumomab-related treatment discontinuation occurred in only 13 patients (4.9%).
The safety profile was consistent with clinical trials and previous real-world studies, with no new safety signals identified. The authors note that neurologic events were lower than clinical trial reports, while CRS events were comparable with clinical data.
Additionally, 31 medication errors were reported for 26 patients (9.8%), most commonly administration-related errors due to operator use error and pump malfunction. The authors suggest this highlights the potential of exploring alternative approaches, such as subcutaneous formulations.
The study's large size and inclusion of clinically relevant subgroups strengthen the external validity of these findings, though the authors acknowledge limitations inherent to retrospective real-world analyses, including selection bias, variability in MRD assessment methods, and potential incomplete capture of outcomes occurring outside treating hospitals.