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Brentuximab-R-CHP for CD30+ B-cell lymphomas
Figure 1. CONSORT diagram.
GZL: gray zone lymphoma; cHL: classical Hodgkin lymphoma; EOT: end of treatment.
allowed as per institutional policy. Consolidative radiation thera- py was permitted after completion of all systemic therapy and only after end-of-treatment imaging at the discretion of the treat- ing physician.
Treatment response was assessed by imaging with fluo- rodeoxyglucose-positron emission tomography/computed tomog- raphy (FDG-PET/CT) using the revised response criteria for malig- nant lymphoma described by Cheson et al.25 Computed tomogra- phy scans were performed after cycles 2 and 4 to monitor for inter- im response. End-of-treatment imaging was performed 3-5 weeks after completion of systemic therapy using FDG-PET/CT. Consolidative radiation following end-of-treatment response assessment was permissible at the discretion of the treating physi- cian.
Correlative studies
CD30 expression was determined on the diagnostic tissue biop- sies using immunohistochemistry though visual inspection by two independent pathologists. The gene expression analysis (Lymph3Cx) was performed on archival formalin-fixed, paraffin- embedded tissue from pre-treatment biopsies. The tissue was examined by a hematopathologist for adequate tumor amount and nucleic acids were extracted from formalin-fixed paraffin- embedded scrolls or unstained slides. The Lymph3Cx assay was previously described and validated to aid in the molecular distinc- tion of PMBCL versus DLBCL.26 The gene expression assay on the diagnostic tissue was performed in a blinded fashion, and once the assignment of diagnosis by Lymph3Cx was made, a correlation with investigator-based diagnosis (PMBCL vs. DLBCL vs. GZL) was performed.
Statistical analysis
The overall response rate and complete response rate with a two-sided 95% exact confidence intervals (95% CI) were calculat- ed using the Clopper-Pearson method. Two-year progression-free and overall survival rates were estimated using the Kaplan-Meier method. The median follow-up was estimated by the reverse Kaplan-Meier method.27 The data cut-off for analysis was January 1, 2019.
Results
Patients’ characteristics
Thirty-three patients gave consent to enrollment in the
Table 2. Patients’ characteristics.
All patients (N=31)
Age, years Median
Range
Female Elevated LDH Stage III-IV
Lymphoma subtype PMBL
DLBCL GZL
ECOG PS Median
Range
IPI risk category Low
Low-intermediate High-intermediate High
37 18-76
15 (48%) 21 (68%) 13 (42%)
23 (74%) 6 (19%) 2 (7%)
1
0-2
15 (48%) 11 (36%) 4 (13%) 1 (3%)
LDH: lactate dehydrogenase; PMBCL: primary mediastinal B-cell lymphoma; DLBCL: diffuse large B-cell lymphoma; GZL: gray zone lymphoma; ECOG PS: Eastern Cooperative Oncology Group Performance Status; IPI: International Prognostic Index.
trial (Figure 1). One of these patients was subsequently reclassified from having GZL to having classical Hodgkin lymphoma and was taken off the study before starting therapy. Thus, 32 patients were enrolled and received at least one cycle of therapy. One patient withdrew from the study after cycle 1 to receive R-CHOP therapy closer to home. The characteristics of the patients evaluable for toxicity (n=31) are presented in Table 2. The median age was 37 years (range, 18-76), 50% of the patients were female, 42% had stage III/IV disease and 17% were clas- sified in high-intermediate or high International Prognostic Index (IPI) risk group.28 Using traditional clini- copathological criteria, 23 patients had a diagnosis of PMBCL, six were diagnosed as having DLBCL, and two as having GZL. For the PMBCL cohort, 91% of patients had large mediastinal masses over 7.5 cm in maximal trans- verse diameter and 35% had stage III/IV disease. Two patients were removed from the study (1 patient because of non-compliance and 1 in complete remission because of a regimen violation). Therefore, a total of 29 patients were
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