MVP Combined with FC As Lymphocyte-Depleting Chemotherapy before CAR-T Treatment Can Reduce the Incidence of Severe Cytokine Release Syndrome for Relapsed/Refractory ALL Patients with High Tumour Burden

Background: CAR-T immunotherapy have shown remarkable promising results for relapsed/ refractory (R/R) acute lymphoblastic leukemia(ALL). However, the most common toxicity associated with CD19 CAR-T treatment is Cytokine Release Syndrome(CRS) which can be a life threatening complication especially for high tumour burden ALL patients. How to reduce the incidence of severe CRS can be a great challenge for advanced high tumour patients.

Objective: In order to evaluate the efficacy and safety of MVP+FC as lymphocyte-depleting chemotherapy to reduce tumour burden before CAR-T therapy. Method: If patients' blasts in bone marrow was more than 15%, the chemotherapy MVP(Mitoxantrone 10mg/w once(d1)+ Vindesine 4mg/w once(d1) + Dexamethasone 10mg/d×7d(d1-d7)followed by FC(Fludarabine 30mg/m²× 3d (d8- d10)+ cyclophosphamide 300mg/m²×3d(d8-d10))were performed. CD19 CAR-T were infused with dose escalation schedule: 10%--40%--60%(d13,d14,d15). Total dose of CD19 CAR-T was 5×10⁶/kg.

Results: Seven patients were enrolled in this study with median age of 22 ( 7-46) years old. Three patients were relapse post multiple chemotherapies. Another 4 patients were relapse post allo-HSCT including T315I and TP53 mutation patients. The median blasts in BM before and after MVP treatment were 43.5% (15-87%) and 24%(0-40%).Furthermore, the median blasts in BM after MVP+FC treatment were 4%(0-52%). Overall response of CAR-T were 86% with hematological remission 86% and molecular remission 71%.Only 1 patient experienced 3 grade CRS and other patients just had 1-2 grade of CRS. Only one presented sepsis.No one experienced neurotoxicity. The median duration of neutropenia was 5.5(2-18)days. Treatment related mortality was 0.With the median follow up of 8(1-17)months, both 6 and 12 months leukemia free survival were 47.62%. The accumulative relapse rate was 52%.

Conclusion: MVP combined with FC was an effective and safety conditionning regimen before CAR-T treatment with low incidence of severe CRS especially for high tumour burden ALL patients.