PS948 EXCELLENT RESPONSE TO BLINATUMOMAB IN REFRACTORY B LINEAGE ACUTE LYMPHOBLASTIC LEUKAEMIA IN CHILDREN AND YOUNG ADULTS AFTER DEBULKING CHEMOTHERAPY TO ACHIEVE PARTIAL REMISSION
Authors: Clesham K. , Rao V. , Bartram J. , Ancliff P. , Ghorashian S. , O’Connor D. , Pavasovic V. , Rao A. , Samarasinghe S. , Cummins M. , Marks D. , Taylor G. , Nicholson E. , Macartney C. , Patrick K. , Bonney D. , Gibson B. , Vora A. 
Published: June 2019

Background:

A recent phase I/II study of blinatumomab in children with relapsed/refractory B cell acute lymphoblastic leukaemia (B‐ALL), found 39–51% achieved complete, often MRD negative, remission after two cycles of therapy. Higher responses were observed in patients with less than 50% bone marrow blasts, compared to greater than 50% (55.6% vs 32.7% (95% CI 30.8–78.5 and 20.3–47.1 respectively). Furthermore, an adult study showed complete minimal residual disease (MRD) response rates of 78% when blinatumomab was used to treat MRD‐positive ALL in haematological remission. Hence response rates (and toxicity) to blinatumomab are highly correlated with pre‐treatment disease burden.

Aims:

We aimed to determine the outcome of children and young adults who received blinatumomab for primary refractory or relapsed B‐ALL, who had persistent MRD, or after debulking chemotherapy to achieve a partial remission.

Methods:

Eighteen patients were identified through a national survey. The mean age of patients was 8 years (range 0.5‐ 22), 4 infants and 1 Down syndrome ALL). All patients had B‐lineage ALL which was CD19 positive. None had active CNS disease at the point of receiving blinatumomab. Prior to administration of blinatumomab, all patients either had persistent MRD following several courses of intensive chemotherapy or received debulking chemotherapy for heavier marrow infiltrates. Pre‐blinatumomab chemotherapy to which the patients had failed to obtain an adequate MRD response included UKALL 2011 Regimens A or C, UKALL R3, Interfant 06, FLA‐IDA or NOPHO high risk blocks. Patients received 5–15 μg/m2 of blinatumomab for 1–2 cycles prior to definitive therapy.

Results:

Pre‐blinatumomab, all patients except two were in morphological remission with MRD measurable by PCR (0.003–6%), the remaining patient had 15 and 32% marrow disease by morphology. After 1–2 cycles of blinatumomab all patients had negative MRD when measured by flow cytometry and/or by PCR, giving a 100% response rate. This was followed by haemopoietic stem cell transplant (HSCT) in 17 patients, and of these, 11 are currently alive and disease‐free. Three patients died from transplant‐related complications, without evidence of disease recurrence. One patient had a lineage switch relapse post‐transplant and 2 with CD19 positive relapse 3–7 months post‐transplant have received CART cells. One patient is awaiting CART cells having relapsed 2 weeks after 1 cycle of blinatumomab.

Minimal toxicity was observed; 6 patients had grade 1–2 CRS, which resolved spontaneously without interruption of therapy or treatment with corticosteroids or Tocilizumab. Two patients reported grade neurotoxicity (grade 1+3).

Summary/Conclusion:

This preliminary UK experience demonstrates that excellent MRD response is observed with minimal toxicity in children and young adults who receive blinatumomab for persistent MRD or after debulking chemotherapy which provides an opportunity for transplant in otherwise ineligible patients.