High-dose clarithromycin is an active monotherapy for patients with relapsed/refractory extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT): the HD-K phase II trial.
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.
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.
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Ferreri
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.
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Sassone
Clinical Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
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Kiesewetter
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.
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Govi
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.
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Scarfò
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.
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Donadoni
Clinical Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
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Raderer
D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy; D017291:Clarithromycin / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000188:drug therapy; D018572:Disease-Free Survival; D005134:Eye Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy*; D016879:Salvage Therapy; D012878:Skin Neoplasms / Q000188:drug therapy; D013274:Stomach Neoplasms / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D017291:Clarithromycin
MALT lymphoma; clarithromycin; extranodal marginal zone lymphoma; macrolides