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.
In order to evaluate the efficacy and safety of MVP+FC as lymphocyte-depleting chemotherapy to reduce tumour burden before CAR-T therapy.
If patients’ blasts in bone marrow was more than 28%, the chemotherapy MVP(Mitoxantrone 10 mg/w once(d1)+ Vindesine 4 mg/w once(d1) + Dexamethasone 10 mg/d × 7d(d1-d7) followed by FC(Fludarabine 30 mg/m2 × 3d (d8- d10)+ cyclophosphamide 300 mg/m2 × 3d(d8-d10)) were performed. CD19 CAR-T, CD22CAR-T and CD19CD22 tandem CAR-T were infused with dose escalation schedule: 10%>- 40%>- 60% (d13, d14, d15). Total dose of CAR-T for infusion was 5–10 × 106/kg.
16 patients were enrolled in this study with median age of 24 (6–56) years old. 11 patients were relapse post multiple chemotherapies. Another 5 patients were relapse post allo-HSCT including T315I and TP53 mutation patients. The median blasts in BM before and after MVP treatment were 56% (28–89%) and 34%(0–85%). Furthermore, the median blasts in BM after MVP+FC treatment were 6%(0–60.5%). Overall response of CAR-T were 93.75% with hematological remission 93.75% and molecular remission 63.75%. Only 4 patients experienced 3 grade CRS and other patients just had 1–2 grade of CRS. Only one presented sepsis. No one experienced neurotoxicity. Treatment related mortality was 0. With the median follow up of 9(1–26)months, 6 and 12 months leukemia free survival were 56.9% and 40.6% respectively.
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.