ABSTRACT
INTRODUCTION: Defects in immunologic self-tolerance result in an increased risk for development of paraneoplastic autoimmune diseases (ADs) and immune-mediated toxicity in response to immune stimulation in individuals with thymic epithelial tumors (TETs). We conducted a survey to evaluate the tolerability of coronavirus disease 2019 (COVID-19) mRNA vaccines in patients with TETs, including individuals with preexisting AD. METHODS: After reviewing published data on adverse events associated with the BNT162b2 (Pfizer, Inc., and BioNTech) and mRNA-1273 (ModernaTX, Inc.) mRNA vaccines, we designed and administered a questionnaire to participants at the following three time points: after each dose of vaccination and 1 month after the final dose. Questions related to AD and use of immunosuppressive drugs were included. Descriptive statistics were used to analyze data, and results were compared with previously described results related to the BNT162b2 and mRNA-1273 vaccines. RESULTS: From February 26 to June 1, 2021, we administered the survey to 54 participants (median age = 58 y, thymoma = 33, preexisting AD = 19). Common adverse events included injection site pain, fatigue, and headaches. There were no vaccination-related hospitalizations or deaths. Autoimmune flares occurred in three patients (16%) after the first dose and three patients (17%) after the second dose. Most AD flares were mild and self-limited. One patient (2%) was diagnosed with having a new AD after vaccination. CONCLUSIONS: Tolerability of COVID-19 mRNA vaccines in patients with TETs is comparable to the general population. Most patients with preexisting AD did not experience disease flares, and the development of new AD was rare. Patients with TETs should be encouraged to get vaccinated against COVID-19 owing to the documented benefits of vaccination and manageable risk profile.
ABSTRACT
Background Widespread adoption of vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which causes COVID-19, is a crucial step towards controlling the ongoing pandemic. Messenger RNA (mRNA) vaccines currently authorized for use (BNT162b2 manufactured by Pfizer, Inc. and BioNTech, and mRNA-1273 produced by ModernaTX, Inc., MA, USA) have demonstrated safety, even in individuals with pre-existing autoimmune diseases (AD). Thymic epithelial tumors (TETs) are associated with paraneoplastic AD due to defects in immunological self-tolerance. We conducted a survey to evaluate the tolerability of COVID-19 mRNA vaccines in patients with TETs, including individuals with paraneoplastic AD. Methods After reviewing published data on adverse events (AEs) associated with the BNT162b2 and mRNA-1273 vaccines, we designed a questionnaire to assess tolerability of these vaccines in individuals with TETs. The survey consisted of 13 questions that covered vaccine-related AEs that could be self-assessed by patients. Questions related to AD and use of immunosuppressive drugs were included. The survey was administered at three timepoints: after each dose of vaccination and one month following the final dose. Descriptive statistics were used to analyze data;results were compared with those reported from phase II/III trials of the BNT162b2 and mRNA-1273 vaccines. Results From February 26th, 2021 to June 1st, 2021, 54 patients with TETs participated in the survey [median age: 58 years;females: 26 (48%);thymoma: 33 (61%), thymic carcinoma: 20 (37%);pre-existing AD: 19 (35%);concurrent immunosuppressant use: 12 (22%)]. Common AEs included injection-site pain (57% to 90%), fatigue (21% to 65%), and headaches (16% to 26%). The frequency of muscle- and joint-symptoms was not increased in patients with TETs compared with vaccine trial participants. There were no vaccination-related hospitalizations or deaths. Autoimmune flares occurred in 3 (16%) patients after the first dose and 3 (17%) patients after the second dose. One patient (2%) was diagnosed with a new AD following vaccination. Conclusions Tolerability of COVID-19 mRNA vaccines in patients with TETs is comparable to the general population. Development or flare of autoimmunity is uncommon and manageable. Patients with TETs should be encouraged to get vaccinated against COVID-19 due to documented benefits of vaccination and manageable risks.
ABSTRACT
LESSONS LEARNED: Despite the initial optimism for using immune checkpoint inhibition in the treatment of multiple myeloma, subsequent clinical studies have been disappointing. Preclinical studies have suggested that priming the immune system with various modalities in addition to checkpoint inhibition may overcome the relative T-cell exhaustion or senescence; however, in this small data set, radiotherapy with checkpoint inhibition did not appear to activate the antitumor immune response. BACKGROUND: Extramedullary disease (EMD) is recognized as an aggressive subentity of multiple myeloma (MM) with a need for novel therapeutic approaches. We therefore designed a proof-of-principle pilot study to evaluate the synergy between the combination of the anti-PD-L1, avelumab, and concomitant hypofractionated radiotherapy. METHODS: This was a single-arm phase II Simon two-stage single center study that was prematurely terminated because of the COVID-19 pandemic after enrolling four patients. Key eligibility included patients with relapsed/refractory multiple myeloma (RRMM) who had exhausted or were not candidates for standard therapy and had at least one lesion amenable to radiotherapy. Patients received avelumab until progression or intolerable toxicity and hypofractionated radiotherapy to a focal lesion in cycle 2. Radiotherapy was delayed until cycle 2 to allow the avelumab to reach a study state, given the important observation from previous studies that concomitant therapy is needed for the abscopal effect. RESULTS: At a median potential follow-up of 10.5 months, there were no objective responses, one minimal response, and two stable disease as best response. The median progression-free survival (PFS) was 5.3 months (95% confidence interval [CI]: 2.5-7.1 months), and no deaths occurred. There were no grade ≥3 and five grade 1-2 treatment-related adverse events. CONCLUSION: Avelumab in combination with radiotherapy for patients with RRMM and EMD was associated with very modest systemic clinical benefit; however, patients did benefit as usual from local radiotherapy. Furthermore, the combination was very well tolerated compared with historical RRMM treatment regimens.