Safety and efficacy of clarithromycin monotherapy in patients (pts) with extranodal marginal zone lymphoma (EMZL)

Date

09 Oct 2016

Session

Haematological malignancies

Presenters

Caterina Cecchetti

Citation

Annals of Oncology (2016) 27 (6): 313-327. 10.1093/annonc/mdw375

Authors

C. Cecchetti1, B. Kiesewetter2, M. Sassone1, T. Calimeri1, L. Scarfò1, M. Raderer2, A. Ferreri1

Author affiliations

  • 1 Department Of Oncohematology, IRCCS San Raffaele, 20132 - Milano/IT
  • 2 Univ. Klinik Für Innere Medizin I / Onkologie, Vienna General Hospital (AKH) - Medizinische Universität Wien, 1090 - Vienna/AT
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Background

Evidence revealing anticancer effects of macrolides is growing. Clarithromycin, the most studied one, is safe and active in pts with EMZL (Govi et al. BJH 2010; Ferreri et al. Ann Oncol 2015), but the best administration schedule and dose remain to be defined. We analyzed a retrospective series of 55 pts with EMZL treated with three different regimens of clarithromycin monotherapy, at two institutions, between 2003 and 2015, to establish the best regimen for future trials.

Methods

Clarithromycin regimens were: 500 mg x 2/d, every day, for 6 months (n = 13); 3 cycles of 500 mg x 2/d, days 1-21, q 35 (n = 19); and 4 cycles of 2 g/d, days 1-14, q 21 (n = 23).

Results

Median age was 65 (range 30-88), with a M:F ratio of 0.57. EMZL affected a single organ in 40 pts, and was multifocal in 15: the main involved organs were ocular adnexae (n = 30), stomach (n = 9) and lung (n = 7). IPI score was 0-1 in 40 pts and 2-4 in 15; the IELSG risk score (age, LDH and stage) was 0 in 25 pts, 1 in 23 and >1 in 7. A prior history of HBV/HCV, H. pylori and C. psittaci were recorded in 20 pts; 5 pts had multiple infections. Clarithromycin was the 1st line in 8 pts, the 2nd or more in 47. Tolerability was excellent: the main side effects were grade 1-2 nausea (17), dysgeusia (7), dizziness (4), and headache (3); only 2 pts had grade-3 toxicity (nausea). 5 pts interrupted treatment due to nausea (3), rash or dysgeusia. Nausea was more common in the 2-g/d regimen (52% vs. 25%, p= 0.03). Response was complete in 13 (24%) pts and partial in 13, with an overall response rate (ORR) of 47% (95% CI= 34-60). ORR was higher in pts with gastric lymphoma (78% vs. 41%; p= 0.04). At a median follow-up of 33 months (range 7-137), 29 pts remain progression-free, with a 3-year PFS of 52 ± 7%; refractory disease and IPI ≥2 were independent predictors of poor PFS. Clarithromycin dose was not associated with outcome, with an ORR of 41% after 1 g/d and 57% after 2 g/d (p= 0.24), and a 3-year PFS of 60 ± 9% and 42 ± 10% (p= 0.47), respectively. 52 pts are alive, with a 3-year OS of 96 ± 3%.

Conclusions

Clarithromycin at a dose ≤2 g/d for 4-6 months is active and safe in pts with EMZL. Considering both tolerability and efficacy data, the recommended dose for future lymphoma trials is 1 g/d.

Clinical trial identification

Legal entity responsible for the study

IRCCS San Raffaele Scientific Institute, Milan, Italy

Funding

IRCCS San Raffaele Scientific Institute, Milan, Italy

Disclosure

All authors have declared no conflicts of interest.

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