Handling COVID-19 positive patients with lymphoma from a haematological patient point of view

As there is a lack of evidence-based medicine on COVID-19 management in lymphoma patients, an expert opinion is the sole evidence that can be provided at the moment. Prof. Guidano summarized some of the most recent treatment recommendations for the management of indolent lymphoma, aggressive lymphoma and chronic lymphocytic lymphoma and pointed out some interesting observations in COVID-19 positive lymphoma patients treated with ibrutinib.¹

Management of indolent lymphoma during the COVID-19 pandemic

In indolent lymphoma, the threshold for initiating treatment should be high and watchful waiting should be the preferred strategy whenever possible. If the indication for therapy is borderline, treatment deferral and close monitoring with repeat imaging may be prudent. If a single disease site is of concern, limited radiotherapy is an effective option. There are still concerns about the immunosuppressive properties of bendamustine and as such, R-CVP and R-CHOP might be good alternatives. Maintenance rituximab continues to be prescribed by some of the experts, but not all, and remains a critical and unresolved issue. Patients who are on ‘watchful waiting’ may have visits delayed with telemedicine. For non-Hodgkin lymphoma patients with symptomatic COVID-19, withhold treatment assessing the benefit/risk ratio and consider bridging with steroids.

One important concept that is emerging in indolent lymphoma is the role of Bruton’s tyrosine kinase (BTK) inhibitors during COVID-19 infection, as these drugs may mitigate the cytokine release syndrome triggered in alveolar type II cells. As observed in a case series of six Waldenström’s macroglobulinaemia patients on ibrutinib, this drug may provide protection against lung injury and even improve pulmonary function in hypoxic patients with COVID-19.² For the moment, these data are only hypothesis-generating and clinical trials with BTK-inhibitors are now in progress in the COVID-19 context.

Management of aggressive lymphoma during the COVID-19 pandemic

In aggressive lymphoma, R-CHOP continues to be the standard of care for diffuse large B-cell lymphoma. For those who are at high-risk for CNS involvement, the addition of two cycles of high-dose methotrexate is recommended. In patients who have already started therapy, treatment should not be changed and telemedicine should replace all visits that are not coincident with treatment. Oral regimens (e.g. lenalidomide) are being utilized by some experts in the relapsed/refractory setting. HDC/autoHSCT remains the standard-of-care for patients with relapsed/refractory disease and outpatient regimens are an alternative for non-transplant eligible patients as well. Finally, there are some theoretical concerns that filgrastim may exacerbate the respiratory effects of COVID-19 infection, but as of yet there is no contraindication to growth factor support in patients anticipated to become neutropenic.

Of note, in patients with lymphoproliferative diseases, the virus might reactivate after a period of SARS-CoV-2 clearance and become positive again with a low burden of viral load. Therefore, as the immune system is most likely less effective, the usual two weeks for retesting may not be sufficient in patients with lymphoproliferative disorders.

Management of CLL during the COVID-19 pandemic

For the management of patients with CLL, the patients’ exposure to potential nosocomial SARS-CoV-2 infection should be limited by minimizing the number of visits, postponing in-hospital routine follow-up appointments and substituting them with telemedicine. For patients in need of treatment, the initiation of treatment should be postponed, if possible, until the epidemic trajectory is decreasing. When treatment cannot be further deferred, the systemic treatment that requires the fewest clinic visits and/or is the least immunosuppressive should be preferred. In addition, all patients, also those who are asymptomatic, should be tested for SARS-CoV-2 infection by a nasopharyngeal swab 72-24 hours before the start of CLL therapy. Treatment with targeted agents in patients lacking COVID-19 symptoms can be continued as in normal circumstances, with the exception of anti-CD20 antibodies. In patients on treatment for CLL, who receive a COVID-19 diagnosis, holding therapy until the recovery from infection is a prudent approach. Targeted agents can be resumed if all of the following conditions are met: i) the patient is asymptomatic for at least 48 hours, ii) at least 14 days have elapsed from symptoms starts, iii) at least two consecutive RT-PCR tests are negative on nasopharyngeal swab samples collected each approximately one week apart. Finally, doctors taking care of patients with CLL must be prepared for possible outbreaks of the infection and adapt the management of patients with CLL accordingly.

Interestingly, as evidenced by a series of CLL patients of the Hospital Clinic in Barcelona, only a low percentage of these patients got diagnosed with symptomatic COVID-19 (4 out of 420 patients, 0.95%). In addition, all four patients had a mild disease course and no patient required admission to the intensive care unit. Nevertheless, this seemingly low prevalence of symptomatic COVID-19 in CLL needs to be taken cautiously and future studies are mandatory.

Consistent with what was observed for ibrutinib in patients with Waldenström’s macroglobulinaemia, two CLL patients with COVID-19 who continued on ibrutinib had short hospital stays, minimal oxygen requirements and have since fully recovered.

General measures for patients with cancer in COVID-19 endemic areas

Stronger personal protection provisions should be made for patients with cancer or cancer survivors and a more intensive surveillance or treatment should be considered when patients with cancer are infected with SARS-CoV-2, especially in older patients or those with other comorbidities. Clinical activities and management should be adapted to the phase 2 of the pandemic and one should learn from the recent past to be prepared in case of recrudescence of the pandemic.

References

1. Gaidano G. Handling patients – hematological patient point of view (lymphoma). Presented at EHA 2020; Oral presentation pq282-3.
2. Treon SP, Castillo JJ, Skarbnik AP, et al. The BTK Inhibitor Ibrutinib May Protect Against Pulmonary Injury in COVID-19-infected Patients. Blood. 2020;135:1912-15.