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.

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.