COVID-19 and Hodgkin Lymphoma: Frequently Asked Questions
(Version 4.0; last updated November 30, 2020)
Input from Drs. Ranjana Advani, Nancy Bartlett, Leo Gordon, Kara Kelly, Peter Johnson, Kerry Savage, Laurie Sehn, and Jane Winter
Note: Please review ASH's disclaimer regarding the use of the following information.
There appeared to be more consensus regarding treatment for Hodgkin Lymphoma than other lymphoma subtypes likely because of the curative nature of treatment and the relatively young demographic. There has been concern that bleomycin lung toxicity might be especially problematic during the pandemic, and that strategies to reduce the risk of bleomycin pneumonitis should be prioritized in all stages of disease and age groups. Many centers are screening all patients beginning therapy in the out-patient clinic 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.
As flu season approaches, patients should be encouraged to be vaccinated for the flu and cautioned to follow recommendations for reducing risks of contracting COVID-19. Patients undergoing treatment may have attenuated responses to vaccination for influenza and for COVID-19. Nonetheless, when available, vaccination for SARS-COV2 infection is recommended. The high morbidity and mortality rates reported in patients with hematologic malignancies underscore the vulnerability of this patient population.
Are you changing your approach to initial therapy?
Overall, the treatment approach for Hodgkin lymphoma has not been impacted significantly in the front-line setting. There are however instances in which there are multiple treatment alternatives with different toxicity profiles or requirements for hospital visits. Whether treatment with checkpoint inhibitors will increase complication rates from SARS-CoV-2 is unknown.
...For early stage, favorable disease?
For early favorable disease two cycles of ABVD and limited radiotherapy (20 Gy) remains an option, but requires multiple visits for radiotherapy, more than the alternative of ABVD X 4 with an interim PET/CT. However, modifications to radiotherapy dose and schedule for the COVID-19 emergency have recently been published (See recently posted ILROG guidelines referenced below). Many centers already have moved to omitting bleomycin in early stage patients after a negative interim PET extending the RATHL data to early stage favorable patients, thereby reducing risk.
...For early stage, unfavorable disease?
ABVD X 4 -6 with an interim PET/CT or ABVD X 4 + ISRT (see modifications in dose and fractionation from ILROG referenced below), with the former preferred because of the fewer number of visits. Again, omission of bleomycin after a negative PET/CT is recommended. Judicious use of growth factor (see below) and prophylactic antibiotics will also limit toxicities and the need for hospital visits and admissions.
...For advanced stage disease?
ABVD with an interim PET/CT to allow for elimination of bleomycin in cycles 3 -6 per the RATHL trial continues as the standard of care in most centers. For patients with a positive interim PET/CT, experts are conservative about escalation of therapy (see NCCN guidelines). In the US, an alternative to PET-adapted therapy with ABVD in stage III/IV is AAVD per Echelon-1, replacing bleomycin with brentuximab vedotin, which permits routine growth factor support at the risk of somewhat more neurotoxicity (most reversible), myelosuppression and greater cost (in part attributed to required use of growth factor support).
...For the elderly?
For elderly patients, experts continue to use dose reduced/altered regimens and growth factor support to decrease risk of myelosuppression and hospitalization. The NCCN guidelines provide a list of treatment options for the elderly. Bleomycin should be omitted from therapy in all elderly patients (variably defined; >60 at most centers). Radiotherapy or watchful waiting may be an option for some.
Are you changing therapies for patients who have already started treatment?
The experts have not modified treatment plans already underway but are giving greater consideration to the use of growth factor support, prophylactic antibiotics, and telemedicine visits on days when treatment is not scheduled.
Are you changing therapy to minimize visits? For example, changing to oral or less frequent regimens? Use of radiation?
Unfortunately, treatment intervals for all standard regimens are the same - every two weeks, but whenever possible telehealth is being utilized for patients who don’t have a scheduled treatment. Radiation is already used selectively. Guidelines for altering radiation schedule and dosing to reduce the number of patient visits for those requiring radiotherapy have been published recently (see ILROG guidelines referenced below) . Unfortunately, oral strategies for the treatment of Hodgkin Lymphoma are available only in the palliative setting.
Are you changing your treatment recommendations for relapsed/refractory disease?
Outpatient second line regimens such as gemcitabine-based treatment are being used more commonly rather than regimens that require hospitalization. Some centers are using brentuximab vedotin or PD1 antibodies (administered q4 weeks to reduce visits) when possible instead of chemotherapy and will consider consolidating responses to second line therapy with radiotherapy instead of an autologous peripheral blood stem cell transplant (PBSCT) especially in late relapses. Other centers are proceeding with autoPBSCT. Blood shortages are occurring in some regions and are expected to worsen as the holiday season approaches. Whether patients who become infected with SARS-CoV-2 during treatment with checkpoint inhibitors have worse outcomes than patients with Hodgkin Lymphoma undergoing other treatments is unknown. a Allogeneic stem cell transplant is not commonly used in Hodgkin Lymphoma, but would not be considered in the current situation.
Are you changing your approach to supportive care?
Most experts are recommending more routine use of G-CSF. To avoid increasing the risk of bleomycin pneumonitis, 3 – 5 days of filgrastim mid cycle when prescribing ABVD will eliminate severe neutropenia. Growth factor support is required when AAVD (Echelon-1) is prescribed. Experts are commonly prescribing prophylactic antibiotics for neutropenic patients or those expected to become neutropenic.
For pediatric patients?
Presently, pediatric experts recommend that the standard of care dose intensive treatment regimens with response adapted radiation therapy (ABVE-PC, OEPA/COPDac) not be modified if the chemotherapy agents and relevant supportive care are available. SARS-CoV-2 infection has been described as having a milder clinical course in children than in adults with cancer. Alternatives for low and intermediate risk patients include ABVD with interim PET/CT which requires fewer visits and is associated with less myelosuppression and febrile neutropenia. Omission of bleomycin is recommended after the second cycle for those that are PET negative. For low risk patients with mixed cellularity histology, 3 cycles of AVPC with response adapted radiation therapy may also be considered. For high risk patients, 6 cycles of AAVD (as per ECHELON-1) or ABVD (as per RATHL approach) may be considered. Modifications in radiotherapy dose and schedule for pediatric patients differ from those intended for adults (see reference below). The higher dose per fraction (e.g. 2.5-4 Gy/fraction) recommended by the ILROG for adults is likely to cause more significant late toxicities and should be avoided in pediatric Hodgkin lymphoma patients.
Initiation of chemotherapy for early stage nodular lymphocyte predominant histology may be delayed if necessary.
- ILROG Emergency Guidelines for Radiation Therapy of Hematological Malignancies during the COVID-19 Pandemic.
- Michael Sullivan, Eric Bouffet, Carlos Rodriguez-Galindo, et al. The COVID-19 PANDEMIC: A Rapid Global response for Children with Cancer from SIOP, COG, SIOP-E, SIOP-PODC, IPSO, PROS, CCI and St Jude Global. Authorea. April 25, 2020. DOI: 10.22541/au.158777298.87289192
- 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;371:m3731. Published 2020 Oct 20. doi:10.1136/bmj.m3731