COVID-19 and Hodgkin Lymphoma: Frequently Asked Questions
(Version 2.2; last updated May 4, 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. Some centers are beginning to screen 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.
Are you changing your approach to initial therapy?
Overall, the treatment approach for Hodgkin lymphoma has not yet 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.
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.1 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. PET/CT availability is becoming problematic at some of our centers and its loss will require modifications in our treatment approaches.
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.
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 yet 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 and may require more visits than a chemotherapy alternative. However, emerging guidelines for altering radiation schedule and dosing to reduce patient exposure are under consideration. 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, but looming blood supply shortages will likely make this challenging, at least in the US. Allogeneic stem cell transplant is not commonly used in Hodgkin Lymphoma, but would not be considered in the current situation. Most centers are either suspending enrollment to clinical trials or maintaining a very limited portfolio; it is anticipated that most programs will soon suspend accrual to most if not all clinical trials.
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. 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 not be modified if the chemotherapy agents and relevant supportive care are available. 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 are soon to be published and 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. Link: https://doi.org/10.1182/blood2020006028.
- 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