Abstract
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.
| Pt . | Sex . | Age . | Prior treatments . | Prior SCT . | Bone marrow blast % prior tx . | # of cycles & Reason for discontinuation . | Toxicity . | Bone marrow blast % after tx . | Outcome . |
|---|---|---|---|---|---|---|---|---|---|
| 1 | M | 70 | 1 4 cycles of hyperCVAD, achieved CR Relapse at 9 months post-tx | N | 74% | < 1 Stopped for progressive disease | Grade 1 CRS | 99% blasts in peripheral blood on day 13 | Other salvage chemotherapy Expired |
| 2 | F | 62 | 4 Allogeneic SCT in CR1 Relapse 3.5 years post-SCT | Y | 70% | <2 Stopped on day 17 for sx | Trismus | 83% after cycle 2 | Clinical trial |
| 3 | M | 23 | 5 Allogeneic SCT in CR2 Relapse 1 year post-SCT | Y | 1% | 1 Stopped for alternative clinical trial therapy | HSV-1 lesions Rash | 2% | CAR-T cells followed by second SCT |
| 4 | F | 49 | 1 CALGB induction x 2 cycles with 3% persistent blasts | N | 3% | 1 Stopped for allogeneic SCT | None | MRD negative | Matched sibling donor SCT |
| 5 | M | 64 | 4 Haplo-SCT in CR1 Relapse 9 months post-SCT FLAG salvage to CRi Relapse 4 months post-FLAG | Y | 70% | 2 | Rigors | 93% | Clinical trial |
| 6 | M | 44 | 5 hyperCVAD + maintenance, Relapse 1 year post-maintenance, Salvage with multiple regimens, persistent disease | N | 6% | 2 | Headache | 1% | Haplo-SCT |
| 7 | M | 25 | 4 Pediatric induction, consolidation, maintenance Relapse 2 years post-maintenance, Reinduction achieved CR2, Allo-SCT in CR2 Relapse 1 year post-SCT | Y | 71% | <2 Stopped on day 8 for mental status changes | Mental status changes | 35% | Hospice Expired |
| Pt . | Sex . | Age . | Prior treatments . | Prior SCT . | Bone marrow blast % prior tx . | # of cycles & Reason for discontinuation . | Toxicity . | Bone marrow blast % after tx . | Outcome . |
|---|---|---|---|---|---|---|---|---|---|
| 1 | M | 70 | 1 4 cycles of hyperCVAD, achieved CR Relapse at 9 months post-tx | N | 74% | < 1 Stopped for progressive disease | Grade 1 CRS | 99% blasts in peripheral blood on day 13 | Other salvage chemotherapy Expired |
| 2 | F | 62 | 4 Allogeneic SCT in CR1 Relapse 3.5 years post-SCT | Y | 70% | <2 Stopped on day 17 for sx | Trismus | 83% after cycle 2 | Clinical trial |
| 3 | M | 23 | 5 Allogeneic SCT in CR2 Relapse 1 year post-SCT | Y | 1% | 1 Stopped for alternative clinical trial therapy | HSV-1 lesions Rash | 2% | CAR-T cells followed by second SCT |
| 4 | F | 49 | 1 CALGB induction x 2 cycles with 3% persistent blasts | N | 3% | 1 Stopped for allogeneic SCT | None | MRD negative | Matched sibling donor SCT |
| 5 | M | 64 | 4 Haplo-SCT in CR1 Relapse 9 months post-SCT FLAG salvage to CRi Relapse 4 months post-FLAG | Y | 70% | 2 | Rigors | 93% | Clinical trial |
| 6 | M | 44 | 5 hyperCVAD + maintenance, Relapse 1 year post-maintenance, Salvage with multiple regimens, persistent disease | N | 6% | 2 | Headache | 1% | Haplo-SCT |
| 7 | M | 25 | 4 Pediatric induction, consolidation, maintenance Relapse 2 years post-maintenance, Reinduction achieved CR2, Allo-SCT in CR2 Relapse 1 year post-SCT | Y | 71% | <2 Stopped on day 8 for mental status changes | Mental status changes | 35% | Hospice Expired |
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
