According to the consensus statement of the European Myeloma Network,1 “patients with multiple myeloma (MM) seem to be at increased risk for more severe COVID-19 and associated complications due to their immunocompromised state, the older age, and comorbidities.” We present a case of a patient with 3 different cancers who was diagnosed with SARS-CoV-2 infection and spontaneously eliminated it during current treatment.
A 63-year-old woman was diagnosed with left breast cancer stage IIA (T2 N0 M0) in 2008. In 2019, chondrosarcoma grade 1 was found in Th12 vertebra (Figure 1). She developed acute renal failure (creatinine, 7.8 mg/dl; estimated glomerular filtration rate, 6 ml/min/1.73 m2) due to light chain disease lambda III B stage III according to the International Staging System for Multiple Myeloma. Remission-inducing chemotherapy according to the VTD protocol (bortezomib, thalidomide, dexamethasone) was started. In April 2020, a consecutive dose of bortezomib was administrated just prior to a routine control test for SARS-CoV-2 (a reverse transcriptase–polymerase chain reaction 2-gene test) which yielded a positive result. The patient was asymptomatic, in good general condition, and self-isolated at home. Control tests for SARS-CoV-2 performed 2 weeks later were negative; she did not develop any SARS-CoV-2 antibodies.
The patient continues to receive remission-inducing treatment and dialysis. Selected results of laboratory test performed at the times of MM and SARS-CoV-2 infection diagnosis are presented in Supplementary material, Table S1.
Hereby we report a case of a patient with 3 different malignancies: breast cancer diagnosed several years ago, followed by recently found chondrosarcoma and MM. She was treated with bortezomib, thalidomide, and dexamethasone when asymptomatic SARS-CoV-2 infection was diagnosed. In such scenario, a severe course of COVID-19 would be expected because of profound immunosuppression; in fact, the infection was asymptomatic and disappeared quickly.
The role of Bruton tyrosine kinase inhibitors in the therapy of COVID-19 has been previously discussed. They can be effective in the treatment of COVID-19 due to their anti-inflammatory and antiviral activity. Bruton tyrosine kinase is involved in sustained inflammation through nuclear factor–kappa B (NF-κB) activation, production of proinflammatory cytokines, and cellular senescence, leading to organ damage and spread of viral particles.2
Our patient received bortezomib, which inhibits the NF-κB/IκB transcription factor. Activation of the NF-κB pathway by coronaviruses can increase viral replication and lead to hyperactivation of immune mechanisms such as cytokine storm in SARS-CoV-2 infection.3 Inhibitors of NF-κB improved survival among mice infected with SARS-CoV, which is similar to SARS-CoV-2 in terms of reducing the amount of proinflammatory proteins.4 Suppression of NF-κB may enhance interferon-mediated antiviral activity and improve the disease outcome.2-4 It means that both mechanisms connected with NF-κB can be involved in the therapy with bortezomib in patients with MM and SARS-CoV-2 infection.
In the RECOVERY trial, dexamethasone was the most effective drug among critically ill COVID-19 patients, but not in less severe cases.5 Nevertheless, its anti-inflammatory effect in our patient cannot be excluded.
Although our conclusions may be controversial, we cannot exclude the possibility that the use of bortezomib with dexamethasone in a patient with MM was the reason for the mild course of SARS-CoV-2 infection due to its anti-inflammatory and probably antiviral effect. To our best knowledge, this is the first report suggesting the efficacy of treatment with bortezomib in coronavirus infection.
Agnieszka Zubkiewicz-Kucharska, MD, PhD, Department of Pediatric Endocrinology and Diabetology, Wroclaw Medical University, ul. Chałubińskiego 2a, 50-368 Wrocław, Poland, phone: +48 71 770 31 17, email: agnieszka.zubkiewicz-kucharska@umed.wroc.pl
March 15, 2021.
May 21, 2021.
May 27, 2021.
None declared.
Usnarska-Zubkiewicz L, Augustyniak-Bartosik H, Zubkiewicz-Kucharska A, Knysz B. An asymptomatic course of SARS-CoV-2 infection in a patient with 3 different neoplasms and treated with bortezomib: a coincidence or new therapeutic possibility? Pol Arch Intern Med. 2021; 131: 747-748. doi:10.20452/pamw.16013
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