ABSTRACT
Pegylated-interferon has now replaced interferon-alfa 2a, which is no longer available in the UK, for patients with cutaneous T-cell lymphoma (CTCL) refractory to skin directed therapy. We present our experience of treating 12 CTCL patients with pegylated-interferon. A retrospective review of patients with CTCL from November 2019 to June 2021 treated with pegylated-interferon at a cancer centre in the UK. Twelve patients were included in the review, eight males and four females. Patients were between 48 and 84 years old with Stage IIA-IIB mycosis fungoides. Patients received a selection of prior treatments;PUVA, UV-B, gemcitabine, bexarotene, total skin electron beam therapy, localised radiotherapy, topical steroids and retinoids. All patients were started on a weekly dose of 135 μg pegylated interferon. Nine patients demonstrated a significant improvement in skin appearance and symptoms. Four patients were subsequently escalated to 180 μg due to a diminished response and one patient was dose reduced to 90 μg due to weight loss. The duration of Pegylated-interferon ranged from 1 to 17 months with six patients currently still on treatment. One patient developed progressive disease over the first month and required intravenous chemotherapy to establish control. The median time to response was 42 days. Pegylated interferon was well tolerated and no patients discontinued treatment due to toxicity. Three patients reported no significant side effects. Four patients reported mild coryzal or flu-like symptoms. Two patients reported mild gastrointestinal symptoms. One patient suffered hot flushes, shedding and thinning of the hair that was initially troublesome but subsequently settled. One patient required a 20-week interruption due to stomach pains, bowel disturbance, dizziness and breathlessness all of which resolved. Similar symptoms were previously reported in the same patient on interferon alpha-2a. One patient suffered a pulmonary embolism 13 weeks into treatment which was successfully managed. One patient died following a stroke after 36 weeks of treatment and was confirmed COVID positive. Seven patients received interferon alpha 2a prior to pegylated-interferon. Two patients were converted directly and demonstrated an improved response. One patient reported new unilateral hearing loss that resolved with ear drops, and one patient reported tinnitus and poor appetite that also resolved. Otherwise, there were no significant differences in side effects and response was maintained. The substitution of Pegylated-interferon for alpha interferon was associated with a high response rate with no evidence of additional toxicity. [ABSTRACT FROM AUTHOR] Copyright of European Journal of Cancer is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
ABSTRACT
Passive immunization using monoclonal antibodies will play a vital role in the fight against COVID-19. The recent emergence of viral variants with reduced sensitivity to some current antibodies and vaccines highlights the importance of broad cross-reactivity. This study describes deep-mining of the antibody repertoires of hospitalized COVID-19 patients using phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralizing antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded a panel of potent neutralizing antibodies which bind distinct viral epitopes including epitopes conserved in SARS-CoV-1. Structural determination of a non-ACE2 receptor blocking antibody reveals a previously undescribed binding epitope, which is unlikely to be affected by the mutations in any of the recently reported major viral variants including B.1.1.7 (from the UK), B.1.351 (from South Africa) and B.1.1.28 (from Brazil). Finally, by combining sequences of the RBD binding and neutralizing antibodies with the B cell receptor repertoire sequencing, we also describe a highly convergent early antibody response. Similar IgM-derived sequences occur within this study group and also within patient responses described by multiple independent studies published previously.