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(Version 6.0; last updated April 1, 2022)

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; 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 for SARS-CoV-2 when beginning therapy in the outpatient clinic or on admission to the hospital for treatment. Practices differ depending on the prevalence of COVID-19. The decision on when and how to treat Hodgkin lymphoma in the face of a positive result must be individualized.

Patients, their families, 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. Patients undergoing treatment may have attenuated responses to vaccination for influenza and for COVID-19. Nonetheless, vaccination for SARS-CoV-2 infection is recommended. The high morbidity and mortality rates reported in patients with hematologic malignancies underscore the vulnerability of this patient population. 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?

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, but thus far, there are no indications for concern.

...For early-stage, favorable disease?

For early-stage favorable disease two cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and limited radiotherapy (20 Gy) remains an option, but requires multiple visits for radiotherapy, more than the alternative of ABVD × 4 with an interim positron emission tomography/computed tomography (PET/CT). However, modifications to radiotherapy dose and schedule for the COVID-19 emergency have recently been published (See recently posted International Lymphoma Radiation Oncology Group (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 × 4-6 with an interim PET/CT or ABVD × 4 + involved site radiation therapy (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.

...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 (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine) per Echelon-1, replacing bleomycin with brentuximab vedotin, which requires routine growth factor support at the risk of somewhat more neurotoxicity (most reversible), myelosuppression and greater cost (attributed to the required use of growth factor support as well as brentuximab vedotin).

...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 National Comprehensive Cancer Network guidelines provide a list of treatment options for older patients. 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 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 and/or PD1 inhibitors instead of conventional chemotherapy. For transplant candidates, an autologous peripheral blood stem cell transplant, with its curative potential continues to be the preferred strategy; however, for older patients, consolidation with radiotherapy or continued treatment with checkpoint inhibitors is an option. 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 transplantation is not commonly used in Hodgkin lymphoma, but would not be considered in the current situation unless it is the best alternative.

Are you changing your approach to supportive care?

Growth factor should not be used with ABVD because of the risk of bleomycin toxicity. However, growth factor support is required when AAVD (Echelon-1) is prescribed and is recommended when treating older patients, for whom bleomycin is contraindicated. Experts continue to prescribe growth factor or prophylactic antibiotics in patients undergoing second-line therapy who are anticipated to become neutropenic, or in the setting of escBEACOPP (escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone).

...For pediatric patients?

Presently, pediatric experts recommend that the standard of care dose-intensive treatment regimens with response-adapted radiation therapy (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide; vincristine, etoposide, prednisone, doxorubicin, cyclophosphamide, dacarbazine) continue to be used for all stages of disease 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 (doxorubicin, vincristine, prednisone, cyclophosphamide) 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-CoV-2 infection for people younger than 5 years is not yet available under the Emergency Use Authorization. Vaccination is currently recommended for patients 5 years or older, their families, and caregivers.

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

Patients with Hodgkin lymphoma, their families, and caregivers should be vaccinated against SARS-CoV-2. Specific to SARS-CoV-2, data regarding the safety and efficacy of vaccines in immunocompromised patients are evolving, but there do not appear to be risks specific to this population. We recommend that patients with Hodgkin lymphoma receive a complete primary series of SARS-CoV-2 vaccine consisting of three vaccinations if an mRNA vaccine, followed by a fourth dose three months later despite the fact that they may not mount a robust immune response. Prophylaxis with long-acting antibodies where available provide an additional level of protection for patients undergoing chemotherapy. For more information about immunocompromised patients and SARS-CoV-2 vaccines, prophylaxis, and treatment, see the ASH FAQ on this topic.

Resources

Yahalom J, Dabaja BS, Ricardi U, et al. ILROG emergency guidelines for radiation therapy of hematological malignancies during the COVID-19 pandemic. Blood. 2020 May 21;135(21):1829-1832. doi: 10.1182/blood.2020006028. PMID: 32275740; PMCID: PMC7243146.

Sullivan M, Bouffet E, Rodriguez-Galindo C, 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.

Hippisley-Cox J, Coupland CA, Mehta N, et al. Risk prediction of covid-19 related death and hospital admission in adults after covid-19 vaccination: national prospective cohort study. BMJ. 2021 Sep 17;374:n2244. doi: 10.1136/bmj.n2244. Erratum in: BMJ. 2021 Sep 20;374:n2300. PMID: 34535466; PMCID: PMC8446717.:m3731.

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