Chemoimmunotherapy With a Modified Hyper-CVAD and Rituximab Regimen Improves Outcome in De Novo Philadelphia Chromosome–Negative Precursor B-Lineage Acute Lymphoblastic Leukemia

Abstract

A B S T R A C T PurposeThe 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 MethodsTwo 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 Ն 20%. ResultsThe 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 Ͻ 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 Ͻ .001% and 75% v 47%, P ϭ .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 ϭ not significant [NS] and 64% v 65%, P ϭ NS, respectively). Older patients with CD20-positive ALL did not benefit from rituximab-based chemoimmunotherapy (rates of CRD 45% v 50%, P ϭ NS and OS 28% v 32%, P ϭ NS, respectively), related in part to deaths in CR. ConclusionThe incorporation of rituximab into the hyper-CVAD regimen appears to improve outcome for younger patients with CD20-positive Ph-negative precursor B-lineage ALL.

CD20 expression has no prognostic role in Philadelphia-negative B-precursor acute lymphoblastic leukemia: new insights from the molecular study of minimal residual disease

“…Since the CD20 and CD19 antigens (the latter being broadly expressed in B-lineage ALL) are useful therapeutic targets in CD20 + ALL, as recently reported by Thomas et al 12 and Topp et al, 13 an additive therapeutic effect from rituximab and/or blinatumomab should be primarily assessed in patients with MRDpos/CD20 + ALL before an allogeneic SCT. …”

Receipt of maintenance therapy is most predictive of survival in older acute lymphoblastic leukemia patients treated with intensive induction chemotherapy regimens

“…It is important to recognize the potential toxicity of intensive chemotherapy, particularly hyperCVAD, which has been associated with prolonged cytopenias when used for the treatment of lymphoid malignancies including ALL [7]. Additionally, an increased incidence of infection has been demonstrated in older compared to younger adult ALL patients receiving standard hyperCVAD [3] as well as hyperCVAD with the addition of either rituximab [8] or anthracycline intensification with or without rituximab [9]. As such, discontinuation of intensive therapy in favor of early maintenance therapy owing to toxicity has been previously reported in older adult patients receiving hyperCVAD [3].…”

Toward Effective Targeted Therapy for the Treatment of Adult Acute Lymphoblastic Leukemia

“…Because ALL cells express a variety of specific antigens, those ones can serve as targets for MoAbs. Following the demonstration of its contribution to change the history of lymphomas, rituximab (anti-CD20) has been the first MoAb to be use with success in adult patients with B-cell lineage ALL in combination with chemotherapy in active and minimal residual disease (MRD) states [10,11]. Recent emerging resistances to rituximab [12] have led to the current development of newer anti-CD20 MoAbs, such as ofatumumab, ocrelizumab and veltuzumab.…”