Introduction: Patients with relapsed/refractory acute lymphoblastic leukemia (ALL) have a poor prognosis and limited treatment options. Blinatumomab was approved in 2014 for the treatment of relapsed/refractory Philadelphia chromosome-negative B-cell ALL. The largest published study of 189 patients with relapsed/refractory B-ALL showed a complete remission/complete remission without hematologic recovery of 43%. Here we report our single center experience in 7 patients with relapsed/refractory B-ALL treated with blinatumomab.

Methods: We reviewed the charts of 7 adult patients with relapsed/refractory ALL. All patients were treated with blinatumomab 9 mcg daily as a continuous infusion on days 1-7, followed by 28 mcg daily as a continuous infusion on days 8 - 28 of a 6 week cycle. For cycle 2, 28 mcg daily as continuous infusion was given on days 1 - 28 of a 6 week cycle.

Patients: The median age was 48 (range 23-70) and included 5 males/2 females. One patient had persistent disease after two cycles of induction (pt 4), 6 had relapsed B-ALL, and 4/6 had prior allogeneic stem cell transplant (SCT).

Results: Two patients (28.6%) had complete remission and received allogeneic SCT in CR, 3 received additional therapy, 2 patient expired soon after blinatumomab. Three of 7 patients (42.9%) were unable to complete 2 cycles: patient 1 for progressive disease on cycle 1 day 13; patient 2 for trismus on cycle 2 day 17; patient 7 on cycle 2 day 8 for mental status changes which recurred after re-challenge. Other toxicities were relatively minor (rigors,headache). One patient (pt 7) developed a venous thromboembolism during the 2 week break period between cycles 1 and 2. Five patients are alive: three in CR post-SCT, one in CRi to other salvage therapy, and one on active therapy in a clinical trial.

Conclusion: The observed response rates in our single center experience are not as high as reported in the clinical trials of blinatumomab in relapsed/refractory B-ALL. We saw responses in patients with MRD as well as one patient who had received 5 lines of prior therapy. It is not uncommon to see responses in clinical practice lower than those observed in a clinical trial. Studies are ongoing to determine the benefit of blinatumomab in other B-ALL settings. Our observed rates of CRS and neurologic toxicity were lower than those previously reported, and our experience suggests that it is relatively well-tolerated. Blinatumomab may be beneficial for some patients with B-ALL and provide a bridge to SCT for those who respond.

Table 1.
PtSexAgePrior treatmentsPrior SCTBone marrow blast % prior tx# of cycles &
Reason for discontinuation
ToxicityBone marrow blast % after txOutcome
70 1
4 cycles of hyperCVAD, achieved CR
Relapse at 9 months post-tx 
74% < 1
Stopped for progressive disease 
Grade 1 CRS 99% blasts in peripheral blood on day 13 Other salvage chemotherapy
Expired 
62 4
Allogeneic SCT in CR1
Relapse 3.5 years post-SCT 
70% <2
Stopped on day 17 for sx 
Trismus 83% after cycle 2 Clinical trial 
23 5
Allogeneic SCT in CR2
Relapse 1 year post-SCT 
1% 1
Stopped for alternative clinical trial therapy 
HSV-1 lesions Rash 2% CAR-T cells followed by second SCT 
49 1
CALGB induction x 2 cycles with 3% persistent blasts 
3% 1
Stopped for allogeneic SCT 
None MRD negative Matched sibling donor SCT 
64 4
Haplo-SCT in CR1
Relapse 9 months post-SCT
FLAG salvage to CRi
Relapse 4 months post-FLAG 
70% Rigors 93% Clinical trial 
44 5
hyperCVAD + maintenance,
Relapse 1 year
post-maintenance,
Salvage with multiple regimens, persistent disease 
6% Headache 1% Haplo-SCT 
25 4
Pediatric induction, consolidation, maintenance
Relapse 2 years post-maintenance,
Reinduction achieved CR2,
Allo-SCT in CR2
Relapse 1 year post-SCT 
71% <2
Stopped on day 8 for mental status changes 
Mental status changes 35% Hospice
Expired 
PtSexAgePrior treatmentsPrior SCTBone marrow blast % prior tx# of cycles &
Reason for discontinuation
ToxicityBone marrow blast % after txOutcome
70 1
4 cycles of hyperCVAD, achieved CR
Relapse at 9 months post-tx 
74% < 1
Stopped for progressive disease 
Grade 1 CRS 99% blasts in peripheral blood on day 13 Other salvage chemotherapy
Expired 
62 4
Allogeneic SCT in CR1
Relapse 3.5 years post-SCT 
70% <2
Stopped on day 17 for sx 
Trismus 83% after cycle 2 Clinical trial 
23 5
Allogeneic SCT in CR2
Relapse 1 year post-SCT 
1% 1
Stopped for alternative clinical trial therapy 
HSV-1 lesions Rash 2% CAR-T cells followed by second SCT 
49 1
CALGB induction x 2 cycles with 3% persistent blasts 
3% 1
Stopped for allogeneic SCT 
None MRD negative Matched sibling donor SCT 
64 4
Haplo-SCT in CR1
Relapse 9 months post-SCT
FLAG salvage to CRi
Relapse 4 months post-FLAG 
70% Rigors 93% Clinical trial 
44 5
hyperCVAD + maintenance,
Relapse 1 year
post-maintenance,
Salvage with multiple regimens, persistent disease 
6% Headache 1% Haplo-SCT 
25 4
Pediatric induction, consolidation, maintenance
Relapse 2 years post-maintenance,
Reinduction achieved CR2,
Allo-SCT in CR2
Relapse 1 year post-SCT 
71% <2
Stopped on day 8 for mental status changes 
Mental status changes 35% Hospice
Expired 

Disclosures

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.

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