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COVID-19 and Hodgkin Lymphoma: 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; Kara Kelly, 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.

There appears 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 for SARS-CoV-2 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.

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 for patients, their families, and caregivers. 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 in patients with Hodgkin lymphoma 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 older patients?

For older 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 older patients (variably defined; > 60 years at most centers). Growth factor support is recommended. 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. 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. 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?

Some experts are recommending more routine use of G-CSF. To avoid increasing the risk of bleomycin pneumonitis, three to five days of filgrastim mid-cycle is used by some to eliminate severe neutropenia when treating with ABVD. Growth factor support is required when AAVD (Echelon-1) is prescribed and is recommended when treating older patients. 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 for all stages of disease and 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 if a total of six cycles is planned. For low risk patients with mixed cellularity histology, three cycles of AVPC with response adapted radiation therapy may also be considered. For high-risk patients, six cycles of AAVD (as per ECHELON-1) or ABVD (as per RATHL approach) may be considered as these approaches are associated with fewer visits for chemotherapy and radiation therapy. 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 incompletely resected, early-stage nodular lymphocyte predominant histology may be delayed if necessary.

Vaccination for SARS-CoV2 infection for people younger than 16 years is not yet available under the Emergency Use Authorization. Vaccination is currently recommended for patients 16 years or older, their families, and caregivers when available.

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

In general, it is considered safe and appropriate for patients with Hodgkin lymphoma to be vaccinated against SARS-CoV2. 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 Hodgkin lymphoma receive a SARS-CoV-2 vaccine although they may not mount a robust immune response. 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. For more information about SARS-CoV-2 vaccines and immunocompromised patients, see the ASH FAQs on this topic.

References

  1. ILROG Emergency Guidelines for Radiation Therapy of Hematological Malignancies during the COVID-19 Pandemic.
  2. 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.
  3. 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.

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