COVID-19 and Indolent Lymphomas: Frequently Asked Questions
(Version 5.0; last updated February 5, 2021)
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.
Whereas treatment for indolent lymphomas and mantle cell lymphoma is not curative, there is more flexibility in approach with a key focus on safety in the setting of COVID-19. The ILROG has recently published emergency guidelines for radiation therapy of hematological malignancies that may be helpful when considering radiotherapy.
Most centers are screening patients beginning therapy in the out-patient clinic or even monthly on an on-going basis, or on admission to the hospital for treatment. Practices differ depending on the prevalence of COVID-19 and the availability of screening. The decision on when and how to treat in the face of a positive result must be individualized. 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 intensive the therapy, the greater the impact on clinical outcomes from COVID-19. Furthermore, patients with lymphoma may have an increased susceptibility to infection with SARS-CoV-2.
Patients should be encouraged to be vaccinated for the flu and cautioned to follow recommendations for reducing risks of contracting COVID-19. The high morbidity and mortality rates reported in patients with hematologic malignancies underscore the vulnerability of this patient population. The extent to which rituximab therapy will impact response to the SARS-CoV-2 vaccines is unknown, but vaccination of patients, their family members and caregivers is recommended. Special considerations are noted below and in the ASH FAQs on this topic.
Are you changing your indications for therapy?
Given COVID-19, the threshold for initiating treatment should be high and watchful waiting should be the preferred strategy whenever possible. Treatment is recommended in symptomatic patients, but if the indication for therapy is borderline, (e.g. if the patient meets GELF criteria but is asymptomatic) treatment deferral and close monitoring with repeat imaging may be prudent. Treatment for asymptomatic patients with rituximab monotherapy is not recommended. Vaccination against SARS-CoV-2 is recommended prior to initiating treatment when feasible. Based on results in immunocompetent patients immunized with the mRNA vaccines, rituximab-containing therapy should be delayed two weeks from the second vaccination (for two-dose vaccines) to allow for the development of neutralizing antibodies and T-cell responses. However, no information is yet available on responses to vaccination in immunocompromised individuals.
Are you changing your approach to initial therapy?
When treatment is indicated, rituximab monotherapy rather than R-chemotherapy should be given consideration. If a single disease site is of concern, limited radiotherapy is an effective option (see ILROG Emergency Guidelines). Many experts have concerns about the immunosuppressive properties of bendamustine and are recommending R-CVP or R-CHOP with growth factor support as alternatives, without rituximab maintenance. Others continue to prescribe R-bendamustine sometimes followed by maintenance but changes in practice are evolving rapidly. The availability of vaccines against SARS-CoV-2 is altering practice and leading many experts to avoid the most immunosuppressive therapies.
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.
Ibrutinib and other Bruton’s tyrosine kinase (BTK) inhibitors continue to be prescribed for chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL) and Waldenstrom macroglobulinemia are options for relapsed mantle cell lymphoma. Ibrutinib is approved for relapsed marginal-zone lymphoma in the United States. Consolidation with high-dose chemotherapy and HCT in mantle cell lymphoma is controversial.
Are you changing therapies for patients who have already started treatment?
For patients who have already achieved an excellent response to R-chemotherapy, a reduced number of cycles may be considered or a switch in therapy to less immunosuppressive or myelosuppressive approaches. Maintenance rituximab continues to be prescribed by some of the experts, but not others. Many have discontinued maintenance rituximab in anticipation of the SARS-CoV-2 vaccines.
Are you changing therapy to minimize visits? For example, changing to oral or less frequent regimens?
Some experts are switching patients to oral options in CLL/SLL, marginal zone lymphoma, or mantle cell lymphoma, rather than continuing intravenous chemotherapy, in an effort to reduce the risk of infection and limit the number of visits to the outpatient clinic. Some patients may be eligible to receive up to a three month supply of their oral medication; this approach, with labs obtained locally and telehealth visits may allow patients to stay at home for the time being. Patients who are on “watchful waiting” may have visits delayed with telemedicine alternatives, with labwork obtained locally or delayed if risk is low.
Are you changing your approach to supportive care?
When choice of therapy is available, options that minimize clinic/chemotherapy outpatient visits are preferred. When feasible, select patients are being reviewed by telehealth to avoid clinic visits. Growth factor support is recommended for patients receiving R-CHOP and may be helpful in select patients who are receiving bendamustine. Patients with comorbidities, recent infections, and low IgG levels, including those who have received rituximab, may benefit from monthly immunoglobulin supplementation if available.
Are you changing your treatment recommendations for relapsed/refractory disease?
Management of relapsed/refractory indolent lymphoma should be based on symptoms and indications for treatment as for previously untreated patients. When possible, experts recommend delaying treatment. When choice of therapy is available, options that minimize clinic/chemotherapy unit visits are preferred. Use of bendamustine, given its immunosuppressive properties, is discouraged by some experts. Oral agents such as BTK inhibitors and lenalidomide with rituximab are options that should be considered. Radioimmunotherapy, where available, is an underutilized option for relapsed/refractory follicular lymphoma.
Should patients with indolent lymphoma receive a vaccine for SARS-CoV-2?
In general, it is considered safe and appropriate for patients with indolent lymphoma to receive the SARS-CoV-2 vaccines. Specific to SARS-CoV-2, data regarding the safety and efficacy of vaccines in immunocompromised patients are not yet available. As a general statement, we recommend that patients with indolent lymphoma receive a SARS-CoV-2 vaccine although they may not mount an effective immune response. For patients receiving rituximab-monotherapy or rituximab-containing regimens, decisions regarding the timing of vaccination must be individualized based on the prevalence of COVID-19 in the community, the patient’s capacity to self-isolate and that of their family members and caregivers, the expected duration of treatment, and the availability of vaccine. Rituximab therapy is expected to blunt or entirely eliminate a humoral response to vaccination for at least three to four months after last exposure. T-cell responses may, however, provide some degree of protection or reduce severity of infection, justifying vaccination during or soon after completion of therapy if available. For more information about SARS-CoV-2 vaccines and immunocompromised patients, see the ASH FAQs on this topic.
- 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.
- AK Clift, Coupland CAC, Keogh RH et al. Living risk prediction algorithm (QCOVIDk) for risk of hospital admission and mortality from coronavirus-19 in adults: national derivation and validation cohort study. BMJ. 2020;371:m3731.