Dataset Information

Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation.

ABSTRACT: Hodgkin lymphoma (HL) relapsing after allogeneic stem cell transplantation (alloSCT) presents a major clinical challenge. In the present investigation, we evaluated brentuximab vedotin, a CD30-directed Ab-drug conjugate, in 25 HL patients (median age, 32 years; range, 20-56) with recurrent disease after alloSCT (11 unrelated donors). Patients were > 100 days after alloSCT, had no active GVHD, and received a median of 9 (range, 5-19) prior regimens. Nineteen (76%) had refractory disease immediately before enrollment. Patients received 1.2 or 1.8 mg/kg of brentuximab vedotin IV every 3 weeks (median, 8 cycles; range, 1-16). Overall and complete response rates were 50% and 38%, respectively, among 24 evaluable patients. Median time to response was 8.1 weeks, median progression-free survival was 7.8 months, and the median overall survival was not reached. Cough, fatigue, and pyrexia (52% each), nausea and peripheral sensory neuropathy (48% each), and dyspnea (40%) were the most frequent adverse events. The most common adverse events ? grade 3 were neutropenia (24%), anemia (20%), thrombocytopenia (16%), and hyperglycemia (12%). Cytomegalovirus was detected in 5 patients (potentially clinically significant in 1). These results support the potential utility of brentuximab vedotin for selected patients with HL relapsing after alloSCT.

SUBMITTER: Gopal AK

PROVIDER: S-EPMC3731651 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation.

Gopal Ajay K AK Ramchandren Radhakrishnan R O'Connor Owen A OA Berryman Robert B RB Advani Ranjana H RH Chen Robert R Smith Scott E SE Cooper Maureen M Rothe Achim A Matous Jeffrey V JV Grove Laurie E LE Zain Jasmine J

Blood 20120417 3

Hodgkin lymphoma (HL) relapsing after allogeneic stem cell transplantation (alloSCT) presents a major clinical challenge. In the present investigation, we evaluated brentuximab vedotin, a CD30-directed Ab-drug conjugate, in 25 HL patients (median age, 32 years; range, 20-56) with recurrent disease after alloSCT (11 unrelated donors). Patients were > 100 days after alloSCT, had no active GVHD, and received a median of 9 (range, 5-19) prior regimens. Nineteen (76%) had refractory disease immediate ...[more]

PMID: 22510871

Similar Datasets

Project description:BackgroundWe previously demonstrated that brentuximab vedotin (BV) used as second-line therapy in patients with Hodgkin lymphoma is a tolerable and effective bridge to autologous hematopoietic cell transplantation (AHCT). Here, we report the post-AHCT outcomes of patients treated with second-line standard/fixed-dose BV and an additional cohort of patients where positron-emission tomography adapted dose-escalation of second-line BV was utilized.Patients and methodsPatients on the dose-escalation cohort received 1.8 mg/kg of BV intravenously every 3 weeks for two cycles. Patients in complete remission (CR) after two cycles received two additional cycles of BV at 1.8 mg/kg, while patients with stable disease or partial response were escalated to 2.4 mg/kg for two cycles. All patients, regardless of treatment cohort, proceeded directly to AHCT or received additional pre-AHCT therapy at the discretion of the treating physician based on remission status after second-line BV.ResultsOf the 20 patients enrolled to the BV dose-escalation cohort, 8 patients underwent BV dose-escalation. BV escalation was well-tolerated, but no patients who were escalated converted to CR. Of 56 evaluable patients treated across cohorts, the overall response rate (ORR) to second-line BV was 75% with 43% CR. Twenty-eight (50%) patients proceeded directly to AHCT without post-BV chemotherapy, and a total of 50 patients proceeded to AHCT. Thirteen patients received consolidative post-AHCT therapy with either radiation, BV, or a PD-1 inhibitor. After AHCT, the 2-year progression-free survival (PFS) and overall survival were 67% and 93%, respectively. The 2-year PFS among patients in CR at the time of AHCT (n = 37) was 71% compared with 54% in patients not in CR (p = 0.12). The 2-year PFS in patients who proceeded to AHCT directly after receiving BV alone was 77%.ConclusionsSecond-line BV is an effective bridge to AHCT that produces responses of sufficient depth to provide durable remission in conjunction with AHCT (clinicaltrials.gov: NCT01393717).

Project description:Antibody-based immunotherapy has become an integral part of cancer therapeutics. However, monoclonal antibodies have their limitations as identifying an antigen selectively expressed on malignant cells and developing a high-affinity antibody may not by itself alter tumor growth. This is illustrated in the case of CD30; CD30 epitomizes many properties of an ideal pharmacologic target such as high expression on malignant cells and limited expression on normal tissues. However, until the advent of brentuximab vedotin, CD30 remained an elusive target as antibody-based anti-CD30 immunotherapy had been largely clinically unsuccessful. Brentuximab vedotin (cAC10-vcMMAE, SGN-35) is an antibody-drug conjugate consisting of a chimeric anti-CD30 monoclonal antibody whereupon the potent microtubule inhibitor monomethyl auristatin E (MMAE) is attached via a valine-citrulline linker. Once bound to CD30, brentuximab vedotin is internalized and MMAE is released with the action of lysosomal enzymes on the linker. In phase I studies in relapsed or refractory Hodgkin lymphoma and anaplastic large cell lymphoma, brentuximab vedotin induced unprecedented responses with manageable toxicity. In phase II studies, brentuximab vedotin induced overall response rates of 75% and 86% in relapsed or refractory Hodgkin lymphoma and anaplastic large cell lymphoma, respectively. The results of these trials led to the accelerated approval of the drug by the US Food and Drug Administration in a patient population with few other alternative options. Brentuximab vedotin has overall manageable toxicity profile; however, cumulative peripheral neuropathy constitutes an important clinical consideration as it may limit prolonged administration of the drug. The mechanism by which brentuximab vedotin exerts its antitumor activity is not entirely clear. Diffusion of MMAE in the tumor microenvironment and cytotoxicity on bystander cells may in part explain its activity, especially in Hodgkin lymphoma. Herein, we review the biology of CD30 and brentuximab vedotin, and the clinical data that has accumulated thus far with SGN-35.

Dataset Information

Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation.

Publications

Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets