Despite concerns about treatment-related immunosuppression, a report out of Spain suggests SARS-CoV-2 precautions can offset risk for patients with diffuse large B-cell lymphoma.
Even in the midst of a pandemic, successful frontline therapy is still possible for patients with lymphoid malignancies like diffuse large B-cell lymphoma (DLBCL), according to a new journal article.
The short report comes from La Paz University Hospital in Madrid, Spain. Writing in the British Journal of Haematology, de la Cruz-Benito et al explained how they dealt with 18 cases of patients with DLBCL and high-grade B-cell lymphoma (HGBL) as the coronavirus disease 2019 (COVID-19) pandemic spread through the region between March 1 and May 31 of this year.
de la Cruz-Benito and colleagues said they found themselves navigating a number of difficult problems. Lymphoma itself can cause immune deregulation, but many therapies for the cancer cause significant immunosuppression. Thus, continuing with therapy could make a patient even more vulnerable to infection from the SARS-CoV-2 virus, but delaying treatment of lymphoma can also have significant detrimental effects. Additionally, the clinicians at La Paz University Hospital, like physicians everywhere, were operating without clear guidelines, given the novelty of the virus and the dramatic rapidity of its spread.
The study authors said they were most swayed by the potential negative impacts of delaying treatment, and so they set about to adapt their clinical practices in such a way as to continue planned therapy as safely as possible. In addition to screenings for COVID-19 symptoms, patients were not allowed to have visitors in the outpatient area, and follow-up was done via telemedicine whenever possible. Patients receiving immuno-chemotherapy were given SARS-CoV-2 tests before each treatment. Those with DLBCL were treated as outpatients with the R-CHOP (rituximab [Rituxan] plus cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy regimen. Patients with HGBL were treated with the dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride)regimen, with or without rituximab. Elderly patients were given attenuated regimens. Most patients received granulocyte colony stimulating factor (G-CSF) as a prophylactic to prevent neutropenia.
Of the cohort of 18 patients, 15 had DLBCL, the remaining 3 had plasmablastic lymphoma (n = 1) or HGBL not otherwise specified (n = 2).
Only one patient had neutropenic fever, which was observed on day 10 of the first cycle of chemotherapy, she was receiving G-CSF. The patient was given a test for COVID-19, which came back positive. She was then treated with hydroxychloroquine and azithromycin.
“Because of the viral diagnosis, thoracic CT was performed, showing bilateral ground‐glass opacities and 2 consolidations suggestive of viral disease,” the study authors wrote. “Antibiotic treatment with amoxicillin‐clavulanic acid was added, requiring an escalation strategy because of fever persistence, sequentially to levofloxacin (Levaquin), cefepime (Maxipime), and, finally, to meropenem (Merrem) and linezolid (Zyvox), reaching fever defervescence.”
The patient did not require oxygen therapy, and her secondary chemotherapy had to be delayed by 8 days until she had 2 consecutive negative COVID-19 tests.
Lymphopenia, which has been commonly reported among patients with COVID-19, was observed in 16 patients in the study. The patient with COVID-19 had a minimum of 0.05 × 109 lymphocytes/L. Half of the patients with lymphopenia had been treated with R-mini-CHOP.
de la Cruz-Benito and colleagues noted that current guidelines suggest avoidance of intensified regimens in order to decrease immunosuppression and related complications.
“In contrast, our centre decided to keep these regimens, giving priority to reaching the best disease control and outcome,” they wrote, adding that just one of their patients developed COVID-19 during treatment, and the patient had a mild case.
“Our study suggests that, despite maintaining aggressive treatments, it is possible to keep our patients free of COVID-19,” , de la Cruz-Benito et al wrote. “However, further studies are needed to clarify the importance of prior or active chemotherapy in COVID-19 evolution.”
The authors said the issue of lymphopenia and SARS-CoV-2 also requires further investigation.
“It is noteworthy that minimum lymphocyte count was registered in our cohort in the only patient who was infected by SARS‐CoV‐2, simultaneous with the moment of COVID‐19 diagnosis,” they wrote.
Although they suggested that it is probable that the grade of lymphopenia correlates with severity of COVID-19, the only infected patient in their study had a favorable outcome.
More broadly, the authors noted that it was remarkable that only one patient in their cohort required inpatient treatment, suggesting that the use of the febrile neutropenia prophylactic G-CSF “may have influenced the low incidence of COVID-19 in our cohort.”
In their conclusion, the authors wrote that a number of factors, including hygiene, the prophylactic, and patient education could have contributed to their outcomes, but it’s important for health professionals to continue to update guidelines for the treatment of this patient group as more evidence becomes available.
de la Cruz-Benito B, Lázaro-Del Campo P, Ramírez-López A, et al. Managing the front-line treatment for diffuse large B-cell lymphoma and high-grade B-cell lymphoma during the COVID-19 outbreak. Br J Haematol. Published online August 6, 2020. doi:10.1111/bjh.17066