PS1219 CAUSES OF NON – ELIGIBILITY FOR CD19 CAR T‐CELL IMMUNOTHERAPY IN PATIENTS WITH RELAPSE/REFRACTORY DLBCL. EXPERIENCE OF SAINT‐LOUIS HOSPITAL
Authors: PAILLASSA J. , Di Blasi R. , BERNARD S. , DARMON M. , LARGHERO J. , PARQUET N. , BRIGNIER A. , REA D. , MEIGNIN V. , De Kerviler E. , VERCELLINO L. , AZOULAY E. , MADELAINE‐CHAMBRIN I. , BERQUIER M. , THIEBLEMONT C. 
Published: June 2019

Background:

The autologous anti‐CD19 chimeric antigen receptor (CD19 CAR) T‐cells demonstrated significant clinical benefit and a manageable safety profile for patients with relapsed/refractory diffuse large B‐cell lymphoma (R/R DLBCL), with 6‐month ORR at 41–47% and CR at 32–41% in the 3 pivotal clinical trials (ZUMA1, TRANSCEND, JUNO), leading to a rapid approval in third line R/R DLBCL in Europe and in USA. Since April 2018 in France, the CD19 CAR T‐cells Axicabtagene and Tisagenlecleucel are indicated for patients with DLBCL, primary mediastinal B‐cell lymphomas (PMBL) and transformed FL (tFL), recurrent or refractory after ≥ 2 systemic therapy lines; CNS excluded. However, all patients are not eligible to such therapy.

Aims:

We describe the characteristics of the non‐eligible patients and the causes of non‐eligibility for CD19 CAR T‐cells in our center.

Methods:

We performed a retrospective analysis of our registry of patients for whom our center was contacted for a possible treatment with CD19 CAR T‐cells. For each request, a screening form was completed to validate the indication (DLBCL, PMBL or tFL; recurrent or refractory to ≥ 2 systemic therapy lines) and the absence of contra‐indications (CNS involvement (MRI mandatory), active infection). After this first screening, the patient was examined by an expert in lymphoma and CAR T‐cells to check the eligibility criteria: age, comorbidities, LVEF ≥ 45%, no pericarditis or cardiogram abnormality, clearance ≥ 60 mL/min, ALT/AST ≤ 2.5 N, total bilirubin <1.5 mg/dL, no pleural effusion, SpO2 > 92% without oxygen, lymphocytes ≥ 100/μL, no rapid progressive disease (compressive mass, PS > 2 or rapid increase of LDH), no active neurological/auto‐immune disease. In case of severe comorbidities or age> 70, a visit with an ICU physician was performed. The final decision was validated by our local board.

Results:

Between April 2018 and January 31, 2019, 116 requests were analyzed: 38 patients were eligible (35 patients were then infused), 35 patients were rapidly excluded after the first screening because of histology (n = 16), <2 previous therapy lines (n = 2), CNS involvement (n = 5), administrative reasons (n = 13). Overall, 43 patients (37%) with R/R DLBCL were considered as non‐eligible for CAR T‐cells. The median age was 59.5 years old (18–86), 42.5% were > 65 years old. 61.9% were male. There were 38, 4 and 1 patients with DLBCL, PMBL and tFL, respectively. The median number of prior lines was 3 (2–11); 38.2% had > 3 lines. 85% patients presented with a primary refractory DLBCL. 2 patients were previously treated with a high dose therapy with autologous stem cell transplantation (SCT), 2 patients with an allogeneic SCT. The causes of non‐eligibility were: rapid progressive disease (27 patients (rapid increase of LDH 18, PS ≥ 2 9)), comorbidities (7 (renal 1, liver 1, cardiac 3, respiratory insufficiency 2, heavy physical disability 1)), infections (5 (replicative HBV 3, HCV 1, HIV 1)), auto‐immune disease (3 (multiple sclerosis 1, thyroiditis 1, periodic fever syndrome 1)), neurological disease (extrapyramidal syndrome 2), age more than 84 (2), thrombocytopenia (2), no slot available (1), patient refusal (1), and concomitant second cancer (1).

Summary/Conclusion:

In our cohort, one third of patients were eligible, one third rapidly excluded and one third non‐eligible. The three most frequent causes of non‐eligibility were rapid progression (high LDH, bad PS, large mass), comorbidities and active infections.