By Peter Martin, MD
Brentuximab vedotin (BV), is an antibody drug conjugate that selectively binds to a protein called CD30 on the surface of cells (e.g., Hodgkin lymphoma cells) and delivers a payload of toxin (monomethyl auristatin E) directly to that cell; i.e., a Trojan horse approach to cancer therapy. In 2011, the United States Food and Drug Administration (FDA) approved BV based on a phase II trial in which BV demonstrated an overall response rate (ORR) of 75% and complete response rate (CR) of 34% in patients with Hodgkin lymphoma that had relapsed following autologous hematopoietic cell transplantation (AHCT). Given the promising data, investigators at City of Hope and Weill Cornell Medical College-New York collaborated to evaluate the use of BV prior to AHCT. The standard approach for patients that relapse after first-line therapy includes cytotoxic chemotherapy followed by AHCT. However, this approach can be challenging for some patients and may be associated with some short-term and long-term toxicity. Use of BV prior to AHCT may cause patients some side effects and improve their quality of life prior to AHCT. Preliminary data from this trial were presented yesterday at the 56th Annual Meeting of the American Society of Hematology (ASH).
All patients had biopsy proven Hodgkin lymphoma that had relapsed following therapy with ABVD, BEACOPP, or a combination +/- radiation. Patients were treated with a standard dose of BV intravenously every 3 weeks for a maximum of 4 cycles. Over two-thirds of patients responded, including one third of patients that obtained a CR) and roughly half of the patients were able to proceed to AHCT without receiving additional chemotherapy. Treatments were well tolerated by all patients and no transfusions were required or neutropenic fevers developed.
The results from this trial suggest that BV may be an efficacious option as a first line salvage therapy. It is well tolerated and does not hinder stem cell collection or engraftment. Additional studies will be required to confirm these results. Moreover, this study may lay the groundwork for future studies with promising combinations.
By Jia Ruan, MD
The peripheral T-cell lymphomas (PTCL) are uncommon lymphoid diseases that account for 5-10% of all non-Hodgkin lymphomas in adults in North America. Compared to B-cell non-Hodgkin lymphomas, the PTCLs are generally aggressive and less responsive to current treatment options. Relapsed and refractory diseases are common. Novel and target therapies are in much need to improve quality and duration of response. At the 2012 American Society of Hematology (ASH) meeting in Atlanta, several research groups reported encouraging study results with the antibody-drug conjugate Brentuximab vedotin for T-cell lymphomas. Brentuximab vedotin (BV) is an anti-CD30 chimeric antibody conjugated by a protease-cleavable linker to the microtubule-disrupting agent monomethyl auristatin E. BV received accelerated FDA approval in 2011 for relapsed Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), 2 diseases that express abundant CD30. Several new studies have looked at the treatment outcome of BV in patients with systemic or cutaneous T-cell lymphomas that express variable amount of CD30.
Studies in Systemic T-cell Lymphomas
Dr. Jacobsen from Dana Farber Cancer Institute reported an interim analysis of a phase II multicenter study which evaluated the antitumor activity of BV in patients with relapsed or refractory CD30-positive NHL. BV was administered at 1.8 mg/kg every 3 weeks by IV infusion. The study also explored the correlation between antitumor activity and quantitative CD30 expression. Fifty-three patients with various CD30-positive NHLs have been enrolled, including 18 patients with mature T-/NK-cell lymphomas. Of the T-cell lymphoma patients enrolled, 9 have angioimmunoblastic T-cell lymphoma (AITL), 8 have PTCL-NOS, and 1 has cutaneous T-cell lymphoma. The ORR was 27% (3/11) for mature T-/NK-cell NHLs. Thus far, response was particularly noteworthy in in AITL where 3 of 5 patients (60%) have responded (2 CR, 1 PR). Treatment-emergent adverse events were generally mild and moderate (grade 1/2), and expected including peripheral neuropathy and cytopenias, which was consistent with the safety profile of BV. CD30 expression levels for patients with a CR or PR were widely variable and ranged from <1% to 90%. Preliminary data seems to suggest that BV may be beneficial for patients with T-cell lymphomas that have low CD30 expression. Dr. Fanale from MD Anderson Cancer Center reported a phase I study with BV administered concurrently with multi-agent chemotherapy as frontline treatment of systemic ALCL and other CD30 positive T-cell lymphomas. The study was Continue reading “New Treatment for Systemic and Cutaneous T-cell Lymphomas: Antibody-drug Conjugate Brentuximab Vedotin”
By Jia Ruan, MD
Update: The below mentioned trials are closed to enrollment.
The peripheral T-cell lymphomas (PTCL) are a heterogeneous group of lymphoid diseases that constitute less than 15 percent of all non-Hodgkin lymphomas in adults in North America. The most common subtypes are 1) Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS); 2) Anaplastic large cell lymphoma, primary systemic type (ALCL); and 3) Angioimmunoblastic T-cell lymphoma (AITL). The PTCLs are generally aggressive, and tend to run a more relapsing and less favorable clinical course compared to B-cell NHLs. Relapsed and refractory diseases are common. Novel and target therapies are in much need.
At the recent Annual Society of Hematology (ASH) meeting, Dr. Friedberg of the University of Rochester reported the result of a phase 2 trial of Alisertib (MLN8237), a potent inhibitor of aurora A kinase, in patients with relapsed aggressive non-Hodgkin’s lymphoma (NHL). Aurora kinases regulate mitosis during cell division. Inhibition of aurora A kinase can lead to mitotic errors and premature cell death. Alisertib is taken orally twice daily for 7 days on 21-day cycles. This phase 2 study enrolled a total of 48 patients, including 8 patients with peripheral T-cell lymphoma. The overall response rate was 32%. Response in T-cell NHL was the most impressive at 57%: four out of eight patients responded, and the some of the responses were durable. The response rates in DLBCL and MCL were modest around 20%. Treatment-related side effects were generally tolerable and included low blood counts, fever, fatigue and inflammation in mouth. Based on these results, additional clinical trials (phase II sponsored by SWOG / NCI and phase III sponsored by Millennium) with this orally available compound are moving forward in T-cell lymphoma. Both of these studies will be available soon at Weill Cornell Medical College (click here to read about the SWOG/NCI trial and click here to read about the Millennium trial on clinicaltrials.gov).
Dr. Advani of Stanford University discussed the updated results of an international phase 2 study of Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large cell lymphoma Continue reading “ASH 2011: New Treatment for T-Cell Lymphoma”