Abstract
Background: Brentuximab vedotin (BV) has shown significant clinical activity in anaplastic large T-cell lymphoma (ALCL). However, the management of those who relapse or have disease progression on BV is challenging. We sought to evaluate the features that may be associated with the response to BV and to assess the outcome after the disease progression. Method: This is a multicenter retrospective study analyzing the outcome of patients who received BV for relapsed or refractory systemic ALCL. A total of 55 patients that had been treated with BV for relapsed or refractory disease were identified. Characteristics at the start of BV were analyzed for their association with failure free survival (FFS) and overall survival (OS). Failure of BV was defined by disease progression, relapse or change of therapy. Patients who received a stem cell transplant (SCT) were censored at the time of transplant for the FFS analysis. Results: The median age of patients at the time of the first cycle of BV was 55 years (range 13–88); most patients were male (82%), and the majority had refractory disease (53%). ALK positive in 14 cases (25%). BV therapy was started within 1 year of the initial diagnosis in 52% of patients. A total of 11 patients (20%) had undergone SCT prior to BV. Overall response rate was 71%, including CR in 45%. With a median follow-up of 30 months, the median FFS was 15 months, and the median OS was not reached. The 2-year FFS and OS was 31% and 59%, respectively. In patients who received BV following failure of primary CHOP (like) therapy, the ORR and CR were 69% and 54%, respectively. Outcomes were similar in patients who had received a prior SCT (2-y FFS 30%, 2-y OS 57%) or had received BV either pre-SCT or were transplant ineligible (2-y FFS 30%, 2-y OS 64%). Twenty-one patients went on to SCT (auto n = 13; allo n = 8) following response to BV. By univariate analyses, PS (0–1 vs >2), sIPI (0–1 vs 2–3 vs 4–5), and interval from diagnosis (≤1 year vs >1) were associated with a shorter FFS. Multivariate analysis showed only sIPI to be independently associated with FFS (Hazard ratio [HR] 2.6, p = 0.004). Univariate analysis for association with OS determined PS, extranodal involvement (≤1 vs >1), high LDH, sIPI, refractory disease (vs relapse) to be associated with shorter OS. Multivariate analysis identified sIPI (HR 3.7, p = 0.001) and refractory disease (HR 2.6, p = 0.036) to be independently associated with OS. Twenty-two patients had PD on BV, and two had treatment tolerance requiring a change in therapy. In this group (n = 24), the median OS after BV failure was only 3 months, and 2-year OS was 30%. Of 6 long-term (>1 year) survivors, five underwent subsequent SCT (allo n = 3, auto n = 2). One had good response to investigational clinical trial treatment, and one had localized indolent disease. Conclusions: Refractory disease to last therapy and higher sIPI at start of BV were associated with inferior outcomes in ALCL following BV. Further, patients with disease progression after use of BV have a dismal outcome. Keywords: anaplastic large cell lymphoma (ALCL); brentuximab vedotin; prognostic indices.
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