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Brentuximab-R-CHP for CD30+ B-cell lymphomas
Figure 4. Correlation of Lymph3Cx results with standard clinicopathological diagnoses made by the investigators. DLBCL: diffuse large B-cell lymphoma; GZL: gray zone lymphoma; PMBCL: primary mediastinal B-cell lymphoma. Patients who progressed are labeled by an arrow. Of 14 patients with PMBCL diagnosed by investi- gator assessment alone, 11 patients (79%) had Lymph3Cx probability scores >0.9, which were consistent with a molecular diagnosis of PMBCL by gene expression analysis, two patients (14%) scored in the indeterminate category (0.1 to 0.9), and one patient (7%) scored as having DLBCL (< 0.1).
cross-trial comparisons of studies, the rate of grade 3 or 4 hematologic and non-hematologic toxicities was similar or lower compared to the rates reported for R-CHOP.17,34 When compared to the DA-EPOCH-R arm from the recently published randomized trial in DLBCL, there appears to be less toxicity with BV-R-CHP in our study.17 However, one limitation of this comparison is the younger median age of patients in our cohort. Neuropathy is of particular concern with a BV-containing regimen and was closely monitored in our study. While peripheral sensory neuropathy was reported in 61% of patients, no patient experienced grade 3 or 4 neuropathy. This lack of severe peripheral neuropathy may again relate to the young age of our patients and the fact that our BV-containing regi- men did not contain additional vinca alkaloids, in contrast to some of the other BV-containing combinations used frontline.4,33 There were no unexpected opportunistic infections using the combination of rituximab and BV. The administration of G-CSF was not consistent across the participating institutions in our study, but over 20% of
patients did not require G-CSF at all or its use was limited to one or two cycles. However, considering that 23% of patients experienced febrile neutropenia, empiric use of G-CSF should be considered in patients being treated with BV-R-CHP. With regard to long-term toxicities, one patient developed acute myeloid leukemia 2 years after completing the trial therapy and radiation. It is not possi- ble to determine the association between the protocol treatment and her leukemia, but the fact that the patient’s mother died of acute myeloid leukemia and the patient had normal cytogenetics (rare in secondary leukemias) is suggestive of other contributing factors.
The high rate of thrombosis in the PMBCL cohort is of special interest. Thromboses were found in over one third of PMBCL patients and approximately 50% were diag- nosed prior to initiation of therapy. This high risk of thrombosis in PMBCL patients was described with similar frequency in retrospective studies and is not likely to be related to BV-R-CHP.19,35 This finding warrants further investigations about screening, the potential contribution
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