Farewell to chemotherapy! Ibrevica combined with rituximab in the treatment of megaglobulinemia Fahrenheit (WM) is under review in the United States

June 26, 2018 / BIOON / -- American biotechnology giant abbvie recently announced that the US Food and Drug Administration (FDA) has accepted a supplementary new drug application (SNDA) targeting the anticancer drug imbruvica (ibrutinib, elutinib) and granted the qualification of first priority review The SNDA sought approval for the treatment of megaglobulinemia of Fahrenheit (WM) with imbruvica in combination with rituxan, the Roche anticancer drug If approved, the SNDA will expand the current indications of imbruvica single drug treatment for WM to include combination therapy with rituximab As a single drug therapy, imbruvica is the first and only drug approved by FDA to treat WM This SNDA submission is based on the data of the phase III clinical study, inosovate (pycy-1127) This study is a randomized, double-blind, placebo-controlled study sponsored by pharmacyclics, a subsidiary company of Aberdeen It was carried out in 150 patients with recurrent / refractory and previously untreated (primary treatment, treatment naive) WM who had previously received treatment It evaluated the efficacy and safety of the combination of imbruvica and rituximab compared with rituximab alone In the study, patients received rituximab (375mg / m2, once a week for 4 weeks, once a week for the second 4 weeks after 3 months), all patients received daily oral administration of imbruvica (420mg) or placebo, and continued treatment until reaching the standard of permanent discontinuation The primary end point of the study was progression free survival (PFS), and the secondary end points included overall response rate (ORR), hematological response for hemoglobin determination, time to next treatment (ttnt), overall survival period (OS), and incidence of adverse events as indicators of safety and tolerance in each treatment group The median follow-up of 26.5 months showed that the study successfully reached the primary end point Compared with the single drug group, the PFS rate of imbruvica combined with rituximab group was significantly higher (30 months PFS rate: 82% vs 28%), and the risk of disease progression or death was significantly reduced by 80% (median PFS: not yet reached vs 20.3 months, HR = 0.20, CI: 0.11-0.38, P < 0.0001) It should be noted that the combination of imbruvica and rituximab had longer PFS duration in all relevant subgroups, including primary treatment, relapse, carrying myd88l265p and cxcr4wheim mutations At the same time, the Orr and the main remission rate were significantly increased (92% vs 47%; 72% vs 32% [P < 0.0001]), and the hemoglobin level was significantly improved (73% vs 41%, P < 0.0001) 75% of the patients in the combination group of imbruvica and rituximab continued to be treated, and the median ttnt was not reached yet The duration of treatment in the single drug group of rituximab was 18 months (HR = 0.096, P < 0.0001) The 30-month OS rate was 94% in the combination group and 92% in the single drug group In addition, the data showed that the combination of imbruvica and rituximab also reduced rituximab related infusion response and immunoglobulin M (IgM) flare phenomenon (i.e., a transient increase in blood IgM level) Dr Thorsten Graef, clinical development director of pharmacologics, a company owned by Aberdeen, said that the innovate study provided further evidence of the potential clinical benefits of combination therapy based on imbruvica for patients with WM If approved, this chemotherapy free combination will be another beneficial treatment option for the weight of WM patients (including newly diagnosed and relapsed / refractory), and currently the treatment options in this field are still very limited WM is a rare type of non Hodgkin's lymphoma There are about 2800 cases of WM every year in the United States The disease is characterized by a large number of monoclonal megaglobulin (IgM) in the blood and B-lymphocyte malignant disease characterized by the infiltration of plasma cell lymphoma and bone marrow In January 2015, imbruvica was approved by the US FDA as the first drug to treat WM This drug is suitable for adult patients with WM who have been treated (treated) and have not been treated (initially treated) Imbruvica is a small molecule drug taken orally once a day, which plays an anti-cancer role mainly by blocking the BTK required by the proliferation and metastasis of cancer cells Btk is a key signal molecule in B cell receptor signal complex, which plays an important role in the survival and metastasis of malignant B cells and many other serious aging diseases The drug can block the signal pathway that mediates the uncontrolled proliferation and diffusion of B cells, help kill and reduce the number of cancer cells, and delay the progression of cancer In clinical trials, single drug and combination therapy has shown a strong effect on a wide range of hematological malignancies Accepted for review by U.S FDA with potential to broadband treatment use as a combination treatment option with rituximab in Waldenstr ö M's macroglobulinemia (WM), a rate form of blood cancer