Chlamydophila psittaci eradication with doxycycline as first-line targeted therapy for ocular adnexae lymphoma: final results of an international phase II trial.
OBJECTIVE
The pathogenic association between Chlamydophila psittaci (Cp) and ocular adnexal marginal zone lymphoma (OAMZL) and the efficacy of doxycycline monotherapy have been investigated in retrospective series with variations in stage, management, and follow-up duration. To our knowledge, this is the first international phase II trial aimed at clarifying Cp prevalence and activity of first-line doxycycline in a homogeneous series of consecutive patients with newly diagnosed stage I OAMZL.


METHODS
Forty-seven patients were registered. Tumor tissue, conjunctival swabs, and peripheral blood from 44 patients were assessed for seven Chlamydiaceae infections by three polymerase chain reaction protocols. Thirty-four patients with measurable or parametrable disease were treated with doxycycline and assessed for chlamydial eradication and lymphoma response (primary end point).


RESULTS
Cp DNA was detected in biopsies of 39 patients (89%); no other Chlamydiaceae were detected. Twenty-nine patients had Cp DNA in baseline swabs and/or blood samples and were evaluable for chlamydial eradication, which was achieved in 14 patients (48%). Lymphoma regression was complete in six patients and partial in 16 (overall response rate, 65%; 95% CI, 49% to 81%); 11 had stable disease, and one had progressive disease. At a median follow-up of 37 months (range, 15 to 62 months), 20 patients remained relapse free (5-year progression-free survival [PFS] ± standard deviation, 55% ± 9%). Cp eradication was associated with improved response rate (86% v 47%; P = .02) and 5-year PFS (68% v 47%; P = .11).


CONCLUSIONS
Upfront doxycycline is a rational and active treatment for patients with stage I Cp-positive OAMZL. Lymphoma regression is consequent to Cp eradication, which can easily be monitored on conjunctival and blood samples. Prospective trials aimed at identifying more effective administration schedules for doxycycline are warranted.
San Raffaele Scientific Institute, Milan, Italy. ferreri.andres@hsr.it
Andrés J M
AJ
Ferreri
Silvia
S
Govi
Elisa
E
Pasini
Silvia
S
Mappa
Francesco
F
Bertoni
Francesco
F
Zaja
Carlos
C
Montalbán
Caterina
C
Stelitano
Maria Elena
ME
Cabrera
Antonio
A
Giordano Resti
Letterio Salvatore
LS
Politi
Claudio
C
Doglioni
Franco
F
Cavalli
Emanuele
E
Zucca
Maurilio
M
Ponzoni
Riccardo
R
Dolcetti
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002677:Chile / Q000453:epidemiology; D002691:Chlamydophila psittaci; D004318:Doxycycline / Q000627:therapeutic use*; D005134:Eye Neoplasms / Q000188:drug therapy* / Q000382:microbiology*; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000188:drug therapy / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D009956:Psittacosis / Q000150:complications* / Q000188:drug therapy* / Q000453:epidemiology; D013030:Spain / Q000453:epidemiology; D013557:Switzerland / Q000453:epidemiology; D055815:Young Adult
D000900:Anti-Bacterial Agents; D004318:Doxycycline