Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome-negative precursor B-lineage acute lymphoblastic leukemia

Abstract

Purpose: The adverse prognosis of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia (ALL) prompted incorporation of monoclonal antibody therapy with rituximab into the intensive chemotherapy regimen hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone). Other modifications (irrespective of CD20 expression) included early anthracycline intensification, alterations in number of risk-adapted intrathecal chemotherapy treatments for CNS prophylaxis, additional early and late intensifications, and extension of maintenance phase chemotherapy by 6 months.

Patients and methods: Two hundred eighty-two adolescents and adults with de novo Philadelphia chromosome (Ph)-negative precursor B-lineage ALL were treated with standard or modified hyper-CVAD regimens. The latter incorporated standard-dose rituximab if CD20 expression > or = 20%.

Results: The complete remission (CR) rate was 95% with 3-year rates of CR duration (CRD) and survival (OS) of 60% and 50%, respectively. In the younger (age < 60 years) CD20-positive subset, rates of CRD and OS were superior with the modified hyper-CVAD and rituximab regimens compared with standard hyper-CVAD (70% v 38%; P < .001% and 75% v 47%, P = .003). In contrast, rates of CRD and OS for CD20-negative counterparts treated with modified versus standard hyper-CVAD regimens were similar (72% v 68%, P = not significant [NS] and 64% v 65%, P = NS, respectively). Older patients with CD20-positive ALL did not benefit from rituximab-based chemoimmunotherapy (rates of CRD 45% v 50%, P = NS and OS 28% v 32%, P = NS, respectively), related in part to deaths in CR.

Conclusion: The incorporation of rituximab into the hyper-CVAD regimen appears to improve outcome for younger patients with CD20-positive Ph-negative precursor B-lineage ALL.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Outcomes by therapy for younger patients (age younger than 60 years) with Philadelphia chromosome–negative precursor B-lineage acute lymphoblastic leukemia. In the CD20-positive subset, (A) complete remission (CR) duration and (B) survival by inclusion or exclusion of rituximab therapy, and (C) survival by hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) regimen (standard, modified hyper-CVAD 1 with rituximab inclusive of anthracycline intensification, or modified hyper-CVAD 2 with rituximab eliminating anthracycline intensification) are depicted. (D) Survival by regimen (without rituximab) for the CD20-negative group is also depicted.

Fig 2.

Outcomes by therapy for older patients (age 60 years or older) with Philadelphia chromosome–negative precursor B-lineage acute lymphoblastic leukemia. (A) In the CD20-negative subset, survival by regimen is depicted. (B) In the CD20 positive subset, complete remission (CR) duration (CRD) and survival by rituximab therapy is depicted. OS, overall survival.