The United States Food and Drug Administration (FDA) recently approved brentuximab vedotin in combination with chemotherapy as a first-line treatment for people with advanced-stage classical Hodgkin lymphoma.
Also known as Adcetris, brentuximab vedotin is an antibody drug conjugate that targets the CD30 protein present on lymphoma cells and delivers a toxin designed to promote cancer cell death. The drug has been previously approved to treat systemic anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma that has returned after prior therapy.
The FDA’s approval follows the encouraging results of the phase III ECHELON-1 clinical trial, presented at the 2017 American Society of Hematology (ASH) Meeting and Exposition and published in the New England Journal of Medicine. The trial, which was open at Weill Cornell Medicine and NewYork-Presbyterian Hospital, compared standard therapy with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) versus adriamycin, vinblastine and dacarbazine plus brentuximab vedotin (A+AVD).
Of the 1,300+ enrolled patients, those receiving A+AVD were demonstrated to be 23 percent less likely to experience disease progression, a need for additional therapy, or death, as compared to the cohort receiving the standard of care therapy.
Dr. Peter Martin
“ABVD has been the standard therapy for a couple decades because it works really well, but it’s great to have new treatments available for people with Hodgkin lymphoma,” said Peter Martin, Chief of the Lymphoma Program. “I’m proud that we were able to offer this treatment at Weill Cornell a long time ago through the ECHELON-1 trial. Like any treatment, the A+AVD combination may not be right for everyone and requires consideration of side effects, like infection risk and neuropathy. Decisions between patients and physicians regarding the best treatment should follow an open discussion of the evidence.”
Based on the results of the first in-human clinical trial of ibrutinib in chronic lymphocytic leukemia (CLL) – conducted in 2010 at Weill Cornell Medicine/NewYork-Presbyterian Hospital and other centers – researchers led in part by Dr. Richard Furman moved forward with the first phase II trial of the drug. According to a five-year follow-up study recently published in the American Society of Hematology’s Blood journal, ibrutinib continues to demonstrate excellent efficacy and tolerability as a single agent therapy for people with previously untreated and relapsed or refractory CLL.
CLL is characterized by uncontrolled growth of mature B-cells that accumulate in the blood, bone marrow, lymph nodes and spleen. As CLL cells fill these various organs, they interfere with normal cell functions. Ibrutinib is an oral treatment that inhibits Bruton’s tyrosine kinase (BTK), an enzyme involved in B-cell development that plays a critical role in CLL cell survival.
Prior to the Food and Drug Administration (FDA) approval of ibrutinib for CLL in 2014, chemoimmunotherapy (CIT), typically with fludarabine, cyclophosphamide and rituximab (FCR), was one of the only treatment options available for people with CLL. Chemoimmunotherapy often generates deep responses that last a median of five to six years, but it is associated with significant toxicities. When patients relapse after CIT, their disease becomes more resistant to subsequent treatments, and due to the accumulation of toxicities, many patients are unable to receive further CIT. Given the associated toxicities, the use of CIT is limited in older patients with comorbidities – the cohort that comprises the majority of CLL patients.
The phase II study in which Dr. Furman was involved tested ibrutinib as a single agent in over 100 patients – some of whom received no prior therapy, and others who relapsed following initial treatment. Patients received daily oral doses of ibrutinib until their disease progressed or until the presence of side-effects warranted discontinuation of therapy.
Almost 90 percent of all patient participants demonstrated a response to treatment at the five-year mark, and complete remission rates increased over time with ongoing treatment. Ninety-two percent of treatment-naive patients and 44 percent of relapsed/refractory patients remained free of disease progression five years out from the start of treatment.
Side-effects, including infections, diarrhea, bleeding and low-blood counts, were mild. They did not prevent patients from remaining on treatment long-term and often improved with continued dosing.
Dr. Richard Furman, M.D.
“These data demonstrate the excellent long-term outcomes for CLL patients treated with ibrutinib, especially those who receive ibrutinib as their first therapy,” says Dr. Furman.
The United States Food and Drug Administration (FDA) recently granted accelerated approval to copanlisib for treatment of adults with relapsed follicular lymphoma (FL) who have received at least two prior lines of therapy. Copanlisib is a kinase inhibitor that works by blocking some of the enzymes responsible for cancer cell growth.
The FDA’s decision is based on favorable safety and efficacy results in over 100 patients around the world as part of the CHRONOS-1 clinical trial.
Instead of having to wait years to learn whether a drug actually extends survival for cancer patients, accelerated approval enables the FDA to more quickly approve drugs that fulfill an unmet clinical need for serious conditions. Scientists look to measure surrogate or intermediate clinical endpoints – like tumor shrinkage, for example – that indicate whether a drug is reasonably likely to predict clinical benefit.
As a condition of accelerated approval, a randomized control (comparison) trial will be required to verify the clinical benefit of copanlisib before it can move on to help relapsed follicular lymphoma patients whose treatment options are often limited.
New Developments in Lymphoma 