BMS announces at ASH additional data from PILOT and OUTREACH studies for liso-cel for second-line patients with large B-cell non-Hodgkin�s lymphoma

Bristol-Myers Squibb Company announced data from multiple studies evaluating lisocabtagene maraleucel (liso-cel), an investigational CD19-directed CAR T-cell therapy with a defined composition of purified CD8+ and CD4+ CAR T cells, were presented during the 2019 ASH Annual Meeting in Orlando, Fla. These studies included an evaluation of liso-cel in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) (TRANSCEND CLL 004); a study in second-line patients with relapsed or refractory large B-cell non-Hodgkin�s lymphoma (NHL) patients who were ineligible for high-dose chemotherapy and hematopoietic stem cell transplant (HSCT) (PILOT); and a separate analysis of patients with relapsed/refractory large B-cell non-Hodgkin lymphoma who received liso-cel in the outpatient setting across three studies.

PILOT study : In the phase II PILOT study, patients had relapsed/refractory large B-cell NHL, had received only 1 prior line of immunochemotherapy and had been deemed ineligible for HSCT due to patient factors including age, comorbidities or performance status. Patients received liso-cel at a target dose of 100 � 106 CAR+ T cells following lymphodepletion and could be treated in the outpatient setting at the investigator�s discretion. At the time of data cutoff, 19 patients had been leukapheresed, with 13 patients receiving lymphodepletion followed by liso-cel. Of the 13 patients, eight (61.5%) had at least one grade 3 or higher TEAE and these were primarily cytopenias. Four patients (31%) had prolonged grade 3 or higher cytopenias at day 29. No patients had grade 3 or higher CRS and no patients experienced NE of any grade. Grade 1-2 CRS occurred in 3 (23%) patients. There were no grade 5 TEAEs. Finally, of the 6 patients treated in the outpatient setting, none were admitted to the hospital in the first 29 days following liso-cel infusion. All 12 (100%) patients eligible for response evaluation achieved a response with 6 (50%) patients achieving a CR. Seven of 12 (58%) patients maintained response levels at 3 months following liso-cel infusion.

Outpatient Administration Report including OUTREACH study : A report of the safety and efficacy of liso-cel in patients with relapsed/refractory large B-cell NHL treated in the outpatient treatment setting was also presented. The analysis encompassed three studies including OUTREACH (n=13), the only trial evaluating CAR T-cell therapy in an outpatient setting at non-university centers, including treatment sites not accredited by the Foundation for the Accreditation of Cellular Therapy. The analysis also included TRANSCEND NHL 001 (n=25) and PILOT (n=6). Outpatient treatment required patient education regarding CAR T-cell therapy, a caregiver and proximity to the treatment location. Additionally, each site was required to have specific readiness plans for patient care and monitoring for AEs, such as CRS and NE, in the outpatient setting. In the analysis, at data cutoff, 44 patients treated in the outpatient setting from across the studies were evaluated and received liso-cel on day 1.

Seventeen (39%) patients had CRS of any grade, while 13 (30%) patients had NE (n=13) of any grade. There was 1 case of grade 3 or higher CRS and 2 cases of grade 3 or higher NE and these were reversible. A total of 9 patients received supportive tocilizumab and/or corticosteroids. Fifty-five percent (24/44) of patients required hospitalization at some point and these were all from TRANSCEND or OUTREACH. Of these patients, 9 (20%) were admitted on study day 4 or earlier. Two (5%) patients required intensive care unit-level care lasting a median of 4 days. No patients from PILOT were admitted to hospital in the first 29 days. Following treatment, the median time to hospitalization was 5 days (range 2-22) and the median length of stay was 6.5 days (range 1-23). TEAEs of any grade reported in at least 20% of patients included fatigue, neutropenia, decreased appetite, CRS, anemia, constipation, nausea, headache, cough, dizziness, hypotension, thrombocytopenia, vomiting, back pain, diarrhea hypomagnesemia and tremor. Across the studies, the ORR was 80% (35/44) with 55% (24/44) of patients achieving a complete response. Liso-cel is not approved for any indication in any country.