COVID-19 and Aggressive Lymphoma: Frequently Asked Questions

(Version 6.0; last updated April 1, 2022)

Input from Ranjana Advani, MD; Nancy Bartlett, MD; Ann LaCasce, MD, MSc; Leo Gordon, MD; Peter Johnson, MD, FRCP; Kerry Joanne Savage, BSc, MD, MSc; Laurie Sehn, MD, MPH; and Jane Winter, MD.

Note: Please review ASH's disclaimer regarding the use of the following information.

Testing of symptomatic patients has become routine and most centers screen patients beginning therapy in the out-patient clinic and even monthly or on admission to the hospital for treatment. The decision on when and how to treat lymphoma in the face of a positive result must be individualized. The risk of delaying potentially curative therapy must be weighed against the risk of an adverse outcome from SARS-CoV-2. The degree to which ongoing chemotherapy impacts the outcome of patients with COVID-19 remains controversial, but at least one large study shows that individuals with hematologic malignancies undergoing treatment when diagnosed with COVID-19 are at high risk of severe complications. According to one report, the more intense the therapy, the greater the impact on clinical outcomes in patients who contract COVID-19. The high morbidity and mortality rates reported in patients with hematologic malignancies underscore the vulnerability of this patient population.

Patients, family members, and caregivers should be encouraged to be vaccinated against influenza and SARS-CoV-2 and cautioned to follow recommendations for reducing risks of contracting COVID-19. Special considerations are noted below and in the ASH FAQs on this topic.

Patients undergoing treatment should be encouraged to alert their physicians to new symptoms that could represent SAR-CoV-2 infection so that testing and treatment with oral antiviral therapy or antibodies can be initiated promptly.

Are you changing your approach to initial therapy?

R-CHOP continues to be the standard of care for diffuse, large B-cell lymphoma, with DA-EPOCH-R indicated only for double-hit and primary mediastinal B-cell lymphomas. DA-EPOCH-R is a more toxic regimen as doses are escalated in subsequent cycles based on level of neutropenia and/or thrombocytopenia observed, and it requires hospitalization in most institutions. Whereas bed and staff availability have been compromised by the pandemic, centers with the capacity to deliver this therapy on an outpatient basis are encouraging that approach. Others are weighing benefits and risks for the individual patient with double-hit or primary mediastinal B-cell lymphoma. R-CHOP (or R-CHOP-14) +/- consolidative radiotherapy for some PMBCL patients is an alternative to DA-EPOCH-R but with the additional long-term risks associated with irradiation of the mediastinum, but DA-EPOCH-R is the preferred strategy. (See recently posted ILROG guidelines).

For older patients, R-mini-CHOP with growth factor support continues to be the recommended strategy.

For those who are at high risk for central nervous system (CNS) involvement (CNS-IPI >5, testicular, renal/kidney involvement), institutional policies for CNS prophylaxis are being followed despite the presence of ongoing COVID risk.

For appropriate patients with limited-stage disease, to reduce the number of hospital visits, R-CHOP × 4 is recommended over combined modality therapy.

For those who tolerate the first dose of rituximab given intravenously, subcutaneous administration is an option going forward that reduces time spent in the clinic.

Are you changing therapy to minimize visits? For example, changing to oral or less frequent regimens?

Both physicians and patients have become more comfortable visiting the medical center wearing masks and socially distancing. Overall, telemedicine visits have declined, but they do help to reduce crowding in the outpatient clinic and opportunities for exposure to the very infectious new variants.

Oral regimens are being utilized by some experts in the relapsed/refractory setting and can reduce the number of clinic visits if laboratory testing can be done locally.

Are you changing your treatment recommendations for relapsed/refractory disease?

Most experts continue to offer second-line chemotherapy and high-dose chemotherapy (HDC) or autologous hematopoietic stem cell transplantation (autoHSCT)  for patients with relapsed/refractory disease. Second-line outpatient regimens are preferred when possible and are an alternative for non-transplant eligible patients as well. Oral therapies where appropriate remain an option that may reduce the frequency of visits.

If bed and/or staff availability is an issue, admission for HDC/autoHSCT may be delayed in many instances while another cycle of outpatient chemotherapy is administered. Blood shortages are occurring in some regions and may impact transplant programs.

Because intensive care unit bed availability is variable depending on the status of the COVID-19 pandemic in different parts of the world, the status of chimeric antigen receptor T-cell programs differs according to region. In some locations, treatment may be delayed and salvage therapy prolonged.

Are you changing your approach to supportive care?

Some experts are using growth factor more frequently regardless of age, hoping to prevent trips to the emergency department during the pandemic. 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.

Should patients with aggressive lymphoma receive a vaccine for SARS-CoV-2?

Vaccination with an mRNA SARS-CoV-2 vaccine is recommended, though patients with aggressive lymphoma, especially those receiving B-cell–depleting therapy may not mount an effective immune response. For patients not already fully vaccinated at the time of diagnosis, delaying therapy for vaccination more than two weeks is not recommended, given that longer delays may compromise the curability of treatment. A primary series consisting of three doses of mRNA vaccine is recommended for immunocompromised patients, with a fourth dose three months from the third. Prophylaxis with long-acting antibodies where available provide an additional level of protection for patients undergoing chemotherapy. Although rituximab therapy is expected to blunt or eliminate a humoral response to vaccination for at least nine to 12 months from last exposure (or longer), T-cell responses may provide some degree of protection or reduce severity of infection, justifying vaccination during or soon after completion of therapy. Recent data show that antibody responses achieved prior to treatment can endure through anti–CD20-containing treatment (Shree T et al). Prophylaxis with long-acting antibodies where available provide an additional level of protection for patients beginning treatment for aggressive lymphomas. For more information about immunocompromised patients and SARS-CoV-2 vaccines, prophylaxis, and treatment, see the ASH FAQs on this topic.

Resources

ILROG Emergency Guidelines for Radiation Therapy of Hematological Malignancies during the COVID-19 Pandemic.

Lee, Lennard Y WGault, Abigails et al. COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study. The Lancet Oncology. 2020; Volume 21, Issue 10, 1309 - 1316. Published 2020 Aug 24. DOI: https://doi.org/10.1016/S1470-2045(20)30442-3.

Clift AK, Coupland CAC, Keogh RH, et al. Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study. BMJ. 2020 Oct 20;371:m3731. doi: 10.1136/bmj.m3731.

Shree T, Shankar V, Lohmeyer JJK, et al. CD20-targeted therapy ablates de novo antibody response to vaccination but spares preestablished immunity. Blood Cancer Discov. 2022;3(2): 95-102.

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