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Brentuximab-R-CHP for CD30+ B-cell lymphomas
Efficacy
In the combined phase I/II cohort with 29 evaluable patients, the overall response rate was 100% (95% CI: 88- 100) with 86% (95% CI: 68-96) of patients achieving a complete response and 14% (95% CI: 4-32) achieving a partial response according to FDG-PET/CT imaging at the end of treatment. All four patients with a partial response had a diagnosis of PMBCL and had a low or low-interme- diate IPI risk classification. Only two of the four patients with a partial response ultimately progressed. At a median follow-up of 30 months (95% CI: 26-46), four patients (14%) progressed: three with PMBCL and one with GZL. The 2-year progression-free survival rate was 85% (95% CI: 66-94) and the 2-year overall survival was 100% (Figure 2). Of three patients who were not evaluable per study criteria, two remain progression-free at last follow- up and the status of one patient is unknown.
In the PMBCL cohort of 22 evaluable patients with a median follow-up of 30 months (95% CI: 23-46), the 2- year progression-free survival rate was 86% (95% CI: 62- 95) with a 2-year overall survival of 100% (Figure 2). Of the three PMBCL patients who progressed, two had bulky advanced stage disease with expression of CD30 ≤10% and one had bulky stage I disease with CD30 expression of 1%. There was no statistically significant difference in progression-free survival between the PMBCL patients who received consolidative radiation therapy (n=13) and those who did not (n=9) (P=0.95).
CD30 expression as determined by immunohistochem- istry and response to therapy
While all cases expressed CD30 in at least 1% of the lymphoma B cells in the tumor biopsy by immunohisto- chemistry, it was challenging to capture CD30 expression as a single metric since there was great heterogeneity of CD30 expression patterns, as depicted in Figure 3. Additionally, given the 100% overall response rate and low number of relapses, we could not make any conclu- sions about correlations between efficacy of the BV-con- taining regimen and CD30 expression as determined by immunohistochemistry.
Gene expression analysis to improve diagnostic accuracy of primary mediastinal B-cell lymphoma
Of 29 evaluable patients with CD30+ B-cell lymphoma, 26 had a pre-treatment biopsy available (11 excisional biopsies and 15 core needle biopsies). Of the 26 samples, five core needle biopsies did not have adequate tumor content or amounts of extractable RNA for the Lymph3Cx assay. The biopsies of the remaining 21 patients (11 exci- sional and 10 core needle biopsies) were tested. All three subtypes of CD30+ B-cell lymphomas as assessed by investigator assessment were tested in blinded fashion by the Lymph3Cx assay and comprised 14 cases of PMBCL, six of DLBCL, and one case of GZL. Of 14 patients with PMBCL by investigator assessment alone, 11 patients (79%) had Lymph3Cx probability scores >0.9 which were
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Figure 2. Survival curves for patients who received the BV-R-CHP treatment regimen. (A, B) Progression-free survival (A) and overall survival (B) of all evaluable patients enrolled in the trial (n=29). (C, D) Progression-free survival (C) and overall survival (D) of evaluable patients with primary mediastinal B-cell lymphoma (PMBCL) (n=22).
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