COMPLETE REMISSION WITH BLINATUMOMAB IN TWO PATIENTS WITH SKIN RELAPSED B-CELL ACUTE LEUKEMIA
(Abstract release date: 05/18/17)
EHA Library. Leroy H. 05/18/17; 182343; PB1629
Harmony Leroy
Contributions
Contributions
Abstract
Abstract: PB1629
Type: Publication Only
Background
Blinatumomab is a bispecific T cell–engager (BiTE) antibody (CD19/ CD3) indicated in relapsed/refractory B-cell Acute Lymphoid Leukemia (r/r ALL) (Topp et al.). Extra-medullary relapse is a rare event occurring in only 8% of the patients, of whom only 1.4% present a skin relapse which harbor a dismal prognosis (Gokbuget et al.).
Aims
Herein, we report the efficacy of Blinatumomab in two patients presenting with extra-medullary relapse of ALL.
Methods
The first patient (a 40-year-old man) was diagnosed a CD19+ Ph - B-ALL in 2009. He received a chemotherapy regimen according to the GRAALL protocol (Huguet et al.) until complete remission (CR). In 2015, he presented with a maculopapular rash of the right leg and the left flank, and two enlarged inguinal lymph nodes. Cutaneous relapse was attested by examination of skin biopsy specimen showing a blastic dermal infiltration harboring a CD10+, Tdt+ phénotype. The second patient was a 50-year-old male who presented, in 2016, a CD19+ B-ALL Ph- Ikaros- without central nervous system involvement. He obtained a first CR after GRAALL induction with negative MRD (IgH) but he relapsed 3 months later with a maculopapular rash of his chest. The skin biopsy revealed a blastic dermal infiltration. These two patients with skin relapse received salvage chemotherapy (COPRAALL 2007 regimen) (Domenech et al.), with no efficacy (cutaneous blastic infiltrate). Both patients received one cycle of Blinatumomab from day 1 to day 28, at 28 µg per day, in an attempt to achieve CR before allogeneic stem cell transplantation, as previously described.
Results
At day 5 of Blinatumomab, an important non pruritic maculo-papular rash occurred in both patient, in the same area of the initial cutaneous involvement. Interestingly, it decreased after day 8. No new drug introduction or infection (bacterial, viral or parasitic) was documented in the days preceding or during Blinatumomab infusion. A skin biopsy performed at day 6 of Blinatumomab showed a more prominent dermal CD3+ lymphocytic infiltrate with a perivascular, but also a peri-nervous distribution (on the first patient’s specimen only). Few lymphocytes marginated at the basement membrane and rare basal necrotic keratinocytes were also noted but without blast for the first, although few residual blastic cells were observed on the second’s. One month later, another skin biopsy showed a CR without lymphocytic infiltrate. The medullar CR was confirmed at the molecular level (MRD negative). The first patient received allogenic stem cell transplantation (SCT) from a matched related donor one month later. He presented an acute and chronic GVHD, and is now in complete remission with a follow-up of 7 months. The second is still waiting for a SCT.
Conclusion
These observations confirm the strong efficacy of Blinatumomab in r/r B-ALL. We observed a T-cell dermal recruitment 6 days after Blinatumomab initiation clinically mimicking skin GVHD. However, we couldn’t find specific histological features of GVHD, but only an “inflammatory dermatosis”. Efficacy of Blinatumomab in relapsed B-ALL with cutaneous infiltration suggests promising activity in extra-medullary relapse. Further studies are required to confirm a Blinatumomab-based strategy in extra medullary relapsed B-ALL. This may provide a better understanding of how cytolytic synapses between T lymphocytes and intradermal blasts happen and the underlying homing mechanisms involved.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Relapsed acute lymphoblastic leukemia, Complete Remission, Antigen-specific T cells
Abstract: PB1629
Type: Publication Only
Background
Blinatumomab is a bispecific T cell–engager (BiTE) antibody (CD19/ CD3) indicated in relapsed/refractory B-cell Acute Lymphoid Leukemia (r/r ALL) (Topp et al.). Extra-medullary relapse is a rare event occurring in only 8% of the patients, of whom only 1.4% present a skin relapse which harbor a dismal prognosis (Gokbuget et al.).
Aims
Herein, we report the efficacy of Blinatumomab in two patients presenting with extra-medullary relapse of ALL.
Methods
The first patient (a 40-year-old man) was diagnosed a CD19+ Ph - B-ALL in 2009. He received a chemotherapy regimen according to the GRAALL protocol (Huguet et al.) until complete remission (CR). In 2015, he presented with a maculopapular rash of the right leg and the left flank, and two enlarged inguinal lymph nodes. Cutaneous relapse was attested by examination of skin biopsy specimen showing a blastic dermal infiltration harboring a CD10+, Tdt+ phénotype. The second patient was a 50-year-old male who presented, in 2016, a CD19+ B-ALL Ph- Ikaros- without central nervous system involvement. He obtained a first CR after GRAALL induction with negative MRD (IgH) but he relapsed 3 months later with a maculopapular rash of his chest. The skin biopsy revealed a blastic dermal infiltration. These two patients with skin relapse received salvage chemotherapy (COPRAALL 2007 regimen) (Domenech et al.), with no efficacy (cutaneous blastic infiltrate). Both patients received one cycle of Blinatumomab from day 1 to day 28, at 28 µg per day, in an attempt to achieve CR before allogeneic stem cell transplantation, as previously described.
Results
At day 5 of Blinatumomab, an important non pruritic maculo-papular rash occurred in both patient, in the same area of the initial cutaneous involvement. Interestingly, it decreased after day 8. No new drug introduction or infection (bacterial, viral or parasitic) was documented in the days preceding or during Blinatumomab infusion. A skin biopsy performed at day 6 of Blinatumomab showed a more prominent dermal CD3+ lymphocytic infiltrate with a perivascular, but also a peri-nervous distribution (on the first patient’s specimen only). Few lymphocytes marginated at the basement membrane and rare basal necrotic keratinocytes were also noted but without blast for the first, although few residual blastic cells were observed on the second’s. One month later, another skin biopsy showed a CR without lymphocytic infiltrate. The medullar CR was confirmed at the molecular level (MRD negative). The first patient received allogenic stem cell transplantation (SCT) from a matched related donor one month later. He presented an acute and chronic GVHD, and is now in complete remission with a follow-up of 7 months. The second is still waiting for a SCT.
Conclusion
These observations confirm the strong efficacy of Blinatumomab in r/r B-ALL. We observed a T-cell dermal recruitment 6 days after Blinatumomab initiation clinically mimicking skin GVHD. However, we couldn’t find specific histological features of GVHD, but only an “inflammatory dermatosis”. Efficacy of Blinatumomab in relapsed B-ALL with cutaneous infiltration suggests promising activity in extra-medullary relapse. Further studies are required to confirm a Blinatumomab-based strategy in extra medullary relapsed B-ALL. This may provide a better understanding of how cytolytic synapses between T lymphocytes and intradermal blasts happen and the underlying homing mechanisms involved.
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Relapsed acute lymphoblastic leukemia, Complete Remission, Antigen-specific T cells
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