A team of U.S. researchers has published the results of an in­ves­ti­ga­tion into eyelid-related com­pli­ca­tions in multiple myeloma patients receiving treat­ment with Velcade or Kyprolis. Drawing on the results of their in­ves­ti­ga­tion, the authors of the new study also propose guidelines for the prevention and man­agement of such com­pli­ca­tions.

The authors report on a case series of 16 patients who devel­oped either blepharitis or chalazia after starting treat­ment with Velcade (bor­tez­o­mib) or Kyprolis (car­filz­o­mib).

Blepharitis is the medical term for chronic inflammation of the eyelid, and a chalazion is a cyst in the eyelid caused by a blocked oil gland.

Both blepharitis and chalazia have pre­vi­ously been reported as occurring in patients treated with Velcade, and both Velcade and Kyprolis are in the pro­te­a­some inhibitor class of ther­a­pies, which also in­cludes Ninlaro (ixazomib).

There were 11 women and 5 men in the researchers’ sample of 16 patients, suggesting that eyelid com­pli­ca­tions may be more likely to occur in female myeloma patients.

Fourteen of the 16 patients had one or more episodes of chalazia, and 10 of the patients had one or more episodes of blepharitis. It was common for patients to develop both of the eyelid-related com­pli­ca­tions. This occurred in 60 per­cent of the patients who devel­oped chalazia and 80 per­cent of the patients who devel­oped blepharitis.

The average time from the start of Velcade or Kyprolis treat­ment to the devel­op­ment of an eyelid com­pli­ca­tion was 103 days (3.4 months).

Because the researchers’ report was a retro­spec­tive­ analysis, the patients in their case series did not have their eyelid-related com­pli­ca­tions addressed in a con­sis­tent way. The ap­proach to addressing the com­pli­ca­tions depended on the choice of the patients and their physicians.

In many cases, the eyelid com­pli­ca­tions were addressed solely with what the researchers describe as “ocular ther­apy.” This is treat­ment of the com­pli­ca­tion with warm compresses, oral or in­fused (“systemic”) antibiotics, antibiotic eye drops or ointments, or steroid eye drops or ointments.

In episodes where the researchers were able to document the treat­ment out­come, ocular ther­apy alone suc­cess­fully re­solved the eyelid-related com­pli­ca­tion 70 per­cent of the time.

Another ap­proach to the eyelid-related com­pli­ca­tions was to start ocular ther­apy while also dis­con­tin­u­ing treat­ment with the pro­te­a­some inhibitor the patient was on when the com­pli­ca­tion devel­oped. In episodes with known out­comes, this ap­proach suc­cess­fully re­solved the com­pli­ca­tion 73 per­cent of the time.

Recommendations For Prevention And Treatment

Based on their findings, the researchers propose an algorithm for the prevention and treat­ment of eyelid-related com­pli­ca­tions in patients being treated with Velcade.

As a first step, they rec­om­mend that patients starting treat­ment with Velcade be referred to an ophthalmologist for a base­line screen­ing. They also rec­om­mend that patients be given in­for­ma­tion about eyelid hygiene and the poten­tial for eyelid-related com­pli­ca­tions while being treated with Velcade.

If a patient being treated with Velcade develops chalazia or blepharitis, the researchers rec­om­mend im­medi­ate referral to an ophthalmologist, two months of ocular ther­apy, but no change in myeloma treat­ment. As initial ocular ther­apy, the study authors suggest hot compresses in com­bi­na­tion with at least one topical antibiotic and/or steroid drop.

If this initial ap­proach to the com­pli­ca­tions is not suc­cess­ful, the researchers rec­om­mend that ocular ther­apy be con­tinued, Velcade ther­apy be dis­con­tinued, and con­sid­er­a­tion be given to switching the patient to an alter­na­tive pro­te­a­some inhibitor such as Kyprolis or Ninlaro.

If the com­pli­ca­tions persist even after switching to alter­na­tive myeloma ther­apy, the authors rec­om­mend a prolonged course of the antibiotic doxycycline, admin­istered orally. They also rec­om­mend that a biopsy be carried out to more accurately de­ter­mine the nature of com­pli­ca­tion.

If the com­pli­ca­tions finally re­solve after the patient has been switched to a dif­fer­en­t myeloma ther­apy, the authors suggest that the option of switching the patient back to Velcade be con­sidered.

Study Design And Results

The case series compiled by the study authors in­cluded data for 16 patients seen at Mount Sinai Hospital in New York City. All of the patients had either multiple myeloma (14 patients) or AL amyloidosis with MGUS (2 patients), and they devel­oped eye com­pli­ca­tions be­tween January 2010 and January 2017 while being treated with a pro­te­a­some inhibitor.

The average patient age was 62 years. Median follow-up time was 17 months.

All but one of the 16 patients was receiving a Velcade-containing com­bi­na­tion ther­apy when they devel­oped their first eyelid com­pli­ca­tion. The one non-Velcade patient was on a Kyprolis-containing treat­ment regi­men.

Four of the patients (25 per­cent) devel­oped their first eyelid com­pli­ca­tion during the first cycle of treat­ment. Average time from treat­ment exposure to the onset of the first eyelid com­pli­ca­tion was 3.4 months.

Overall, 14 patients (87.5 per­cent) devel­oped chalazia, 10 patients (62 per­cent) devel­oped blepharitis, and 8 patients (50 per­cent) devel­oped both.

Of the 14 patients who had chalazia, 11 (79 per­cent) devel­oped two or more concurrent lesions. Female patients were more likely to develop concurrent lesions.

The researchers observed 34 episodes of eyelid com­pli­ca­tions in total; 23 of those cases (68 per­cent) were chalazia and 11 cases (32 per­cent) were blepharitis.

The two most common ap­proaches to dealing with these com­pli­ca­tions were ocular ther­apy alone and ocular ther­apy com­bined with stopping the patient’s treat­ment with Velcade.

The most common ocular ther­a­pies were warm compresses (18 episodes), antibiotic eye drops and/or ointments (12 episodes), sys­temic antibiotics (9 episodes), and steroid eye drops and/or ointments (4 episodes).

When ocular ther­apy alone was able to suc­cess­fully address an eyelid-related com­pli­ca­tion, the average time until com­pli­ca­tion resolution was 55 days (1.8 months).

When the com­pli­ca­tion was suc­cess­fully addressed through a com­bi­na­tion of ocular ther­apy and dis­con­tin­u­ing the patient’s original pro­te­a­some inhibitor, the average time until com­pli­ca­tion resolution was 93 days (3.1 months) after dis­con­tinu­a­tion of the patient’s original pro­te­a­some inhibitor.

Five of the 34 episodes of eyelid-related com­pli­ca­tions tallied in the study were not suc­cess­fully re­solved by the time the researchers carried out their analysis of the study results. The authors of the study point out, how­ever, that this was not entirely unexpected because the study follow-up time was just 17 months. The authors there­fore speculate that some of the unresolved episodes may eventually be re­solved.

For more in­for­ma­tion, please see the study by Sklar, B. A. et al., “Management and out­comes of pro­te­a­some inhibitor asso­ci­ated chalazia and blepharitis: a case series,” in BMC Ophthalmology, May 14, 2019 (full text).