A J M Ferreri1, M Sassone2, B Kiesewetter3, S Govi2, L Scarfò2, G Donadoni2, M Raderer3. 1. Unit of Lymphoid Malignancies, Department of Onco-Hematology, San Raffaele Scientific Institute, Milan, Italy Division of Onco-Hematological Medicine, Department of Onco-Hematology, San Raffaele Scientific Institute, Milan, Italy ferreri.andres@hsr.it. 2. Unit of Lymphoid Malignancies, Department of Onco-Hematology, San Raffaele Scientific Institute, Milan, Italy Division of Onco-Hematological Medicine, Department of Onco-Hematology, San Raffaele Scientific Institute, Milan, Italy. 3. Clinical Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
Abstract
BACKGROUND: Clarithromycin displays immunomodulatory and antineoplastic properties. As single agent, this macrolide is associated with tumor responses in anecdotal cases of relapsed/refractory extranodal marginal zone lymphoma (rrEMZL), with a putative dose-dependent effect. Tolerability and activity of high-dose clarithromycin (HD-K) in patients with rrEMZL were addressed in a phase II trial (clinicaltrials.gov NCT01516606). METHODS: HIV-negative adults with rrEMZL and at least one measurable/parametrable lesion were enrolled and treated with four courses of oral clarithromycin 2 g/day, days 1-14, every 21 days. Activity (overall response rate, ORR) was the primary end point. RESULTS: Twenty-three patients were registered (median age 70 years, range 47-88 years; M:F ratio: 0.27). HD-K was given at greater than or equal to second relapse in 11 patients. Ocular adnexae were the most commonly involved organs. Five patients had hepatitis B virus/hepatitis C virus (HBV/HCV) infections; Helicobacter pylori and Chlamydophila psittaci infections were excluded at the time of patient registration.Tolerability was excellent, even among HBV/HCV-positive patients; only two patients had grade >2 toxicity (nausea). Six patients achieved a complete remission and six a partial response (ORR = 52%; 95% confidence interval 32% to 72%). Age, previous treatment and stage did not influence activity. At a median follow-up of 24 (16-33) months, only two patients with responsive disease experienced relapse, with a 2-year progression-free survival of 56 ± 10%; all patients are alive. CONCLUSIONS: HD-K is a safe and active salvage treatment in EMZL patients. This macrolide deserves to be further investigated in EMZL and other lymphoma categories.
BACKGROUND:Clarithromycin displays immunomodulatory and antineoplastic properties. As single agent, this macrolide is associated with tumor responses in anecdotal cases of relapsed/refractory extranodal marginal zone lymphoma (rrEMZL), with a putative dose-dependent effect. Tolerability and activity of high-dose clarithromycin (HD-K) in patients with rrEMZL were addressed in a phase II trial (clinicaltrials.gov NCT01516606). METHODS: HIV-negative adults with rrEMZL and at least one measurable/parametrable lesion were enrolled and treated with four courses of oral clarithromycin 2 g/day, days 1-14, every 21 days. Activity (overall response rate, ORR) was the primary end point. RESULTS: Twenty-three patients were registered (median age 70 years, range 47-88 years; M:F ratio: 0.27). HD-K was given at greater than or equal to second relapse in 11 patients. Ocular adnexae were the most commonly involved organs. Five patients had hepatitis B virus/hepatitis C virus (HBV/HCV) infections; Helicobacter pylori and Chlamydophila psittaci infections were excluded at the time of patient registration.Tolerability was excellent, even among HBV/HCV-positive patients; only two patients had grade >2 toxicity (nausea). Six patients achieved a complete remission and six a partial response (ORR = 52%; 95% confidence interval 32% to 72%). Age, previous treatment and stage did not influence activity. At a median follow-up of 24 (16-33) months, only two patients with responsive disease experienced relapse, with a 2-year progression-free survival of 56 ± 10%; all patients are alive. CONCLUSIONS:HD-K is a safe and active salvage treatment in EMZL patients. This macrolide deserves to be further investigated in EMZL and other lymphoma categories.
Authors: Heimo Lagler; Barbara Kiesewetter; Werner Dolak; Markus Obermueller; Ingrid Simonitsch-Klupp; Julius Lukas; Ortrun Neuper; Wolfgang W Lamm; Marius E Mayerhoefer; Markus Raderer Journal: Hematol Oncol Date: 2018-09-19 Impact factor: 5.271
Authors: Barbara Kiesewetter; Wolfgang Lamm; Ortrun Neuper; Marius E Mayerhoefer; Ingrid Simonitsch-Klupp; Markus Raderer Journal: Hematol Oncol Date: 2019-07-28 Impact factor: 5.271
Authors: Lorenz Thurner; Sylvia Hartmann; Frank Neumann; Markus Hoth; Stephan Stilgenbauer; Ralf Küppers; Klaus-Dieter Preuss; Moritz Bewarder Journal: Front Oncol Date: 2020-12-09 Impact factor: 6.244