The effect of COVID-19 on the management of patients with lymphoma

This article has been prepared for the Lymphoma Hub by Executive Steering Committee Member Stefano Luminari, University of Modena and Reggio Emilia, Reggio Emilia, IT, and provides a summary of recommendations for patients with lymphoma during the COVID-19 pandemic.

The whole medical community is living in an extraordinary and unexpected time, facing the SARS-CoV-2 pandemic. Every medical specialty is currently defining measures and guidelines to manage the risk of infection among patients and during therapy and to issue and update recommendations according to the growing body of available evidence. Lacking a deep knowledge about pathogenesis, clinical features, and effective therapy options for COVID-19, most available recommendations are strongly supporting the adoption of preventive measures to avoid infection in patients and healthcare workers.

Risk to patients with lymphoma

Regarding patients with lymphoma, nothing is known yet about the risk of infection by SARS-CoV-2, apart from that, based on the first cases in China, it has been confirmed as a highly contagious agent. Also, no report is available yet to describe how COVID-19 manifests in patients with lymphoma. There is a general consensus however that patients with lymphoma are identified as being at higher risk of complications as a consequence of SARS-CoV-2 infection, as shown for patients with cancer on a wider scale.

Preventing the risk of infection

For the above reasons, most national and international onco-hematology societies have issued recommendations to protect patients with lymphoma from the risk of SARS-CoV-2 infection. In addition to the rules recommended for the general population, the main actions that are advised are to defer all activities that could increase the risk of infection for the patients. This applies to all clinic visits that are not critical and that could be substituted with telemedicine visits if deemed appropriate and feasible.

Patients undergoing treatment

Regarding ongoing treatments, no recommendation to mandate interruptions have been issued by any society related to lifesaving or ongoing immunochemotherapies. In some settings of non-curative treatments, like maintenance therapy in follicular lymphoma (FL), delaying drug dosing to a time of better control of SARS-CoV-2 spread is a reasonable suggestion.

New treatments

Regarding prescription of new treatments during the SARS-CoV-2 pandemic, no major restrictions have been issued for lifesaving treatments mainly including induction and salvage therapies for aggressive lymphomas. Conversely, for patients with indolent lymphoma, for whom delaying treatment start has been shown to be non-detrimental, a delay in treatment is warranted if feasible. In all patients for whom the decision to start therapy is taken, patients and caregivers should be carefully educated to restrict their risk of exposure to infected individuals as much as possible and to be very careful with hygienic routines, including hand washing and use of alcohol-containing hand sanitizers.

Intensive therapies such as stem cell transplant (SCT)

Most of the above suggestions apply to ambulatory and outpatient therapies, for which a mild to moderate immunosuppression is foreseen with a low and manageable risk of complication. A different scenario is offered by more intensive therapies that are associated with a high risk of complications and a significant risk of severe immunosuppression. This applies to SCT, for which a non-negligible risk of complications requiring admission to intensive care units (ICUs) should be assessed with caution. This is because ICU resources for non-COVID-19 patients might be very limited, or unavailable, during the pandemic.

In this context, it is very important to carefully assess the recommendations of the European Society of Blood and Marrow Transplantation (EBMT) that have recently been published. In addition to the adoption of strict preventive measures for the patients and for the donors of allogeneic SCT, and to recommend SARS-CoV-2 and radiologic testing before and during the procedures, an important recommendation is to postpone the start of the transplant procedure if deemed to be safe to do so.

This last suggestion has important implications for the management of patients with lymphomas, as this applies to both allogeneic and autologous transplants. It is very important to remember that autologous SCT is currently used in different lines of lymphoma treatment but the clinical benefit has only been confirmed, and is supported by high-level scientific evidence, in some of these settings.

Autologous SCT is currently identified as the recommended option for patients with relapsed and refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma. In all other lymphoma subtypes, the use of autologous SCT in the R/R setting is not supported by high quality evidence. 

Moving to first-line therapy, the only indication to support the use of upfront autologous SCT is for young patients with mantle cell lymphoma (MCL); the use of upfront autologous SCT has not been shown to improve patient outcome compared to standard immunochemotherapy in any other lymphoma subtype. Finally, in patients with peripheral T-cell lymphoma, there is a weak consensus to recommend consolidation with autologous SCT in young patients, mostly based on the results of retrospective or phase II trials.

Thus, based on EBMT recommendations and during this phase of SARS-CoV-2 spread, with the only exception being R/R DLBCL, Hodgkin lymphoma, and treatment-naïve MCL, the use of autologous SCT in lymphoma should be considered with caution and possible alternative therapies discussed with the patient. The same applies to allogeneic SCT, which is currently considered as an effective but still experimental option in most lymphoma subtypes and treatment settings.

Finally, in all lymphoma patients for whom SCT indication is confirmed, all possible actions should be implemented in the hospital and at home to avoid the risk of infection prior, during, and after the procedure. Practical recommendations are clearly defined in the EBMT document.