Zainab Shahid, MD, FACP, and Shaji K. Kumar, MD
March 11 marked the 1-year anniversary of the World Health Organization declaring the COVID-19 outbreak a global pandemic. A year later, we are still learning the true impact of this pandemic on the delivery of cancer care globally. Clinical data on COVID-19 cases shows that the presence of hematological malignancies increases the risk of severe disease with SARs-CoV-2 infection along with other co-morbid conditions. Patients with multiple myeloma (MM) don’t have higher risk of acquiring the infection compared to the general population but have increased risk of severe disease. Risk of hospitalization was increased with age greater than 70 years, cardiovascular disease, male sex, and uncontrolled myeloma. Risk of death with COVID-19 increases with age, renal disease, high-risk myeloma, and suboptimal disease control.1-3
As the pandemic set in, medical centers instituted different approaches to reduce the risk of infection among patients with myeloma, and these measures have evolved along with the pandemic with a better understanding of the impact of the disease as well as community transmission rates. Steps initiated early on included a preferential use of oral regimens to decrease visits to clinics, delaying initiation of therapy when possible, delaying stem cell transplantation where appropriate, testing prior to each treatment cycle, using virtual visits combined with local lab testing, and holding accrual to early phase trials with unknown benefit, in addition to the common measures such as social distancing and masking. Over time, especially as it became clear that inadequately controlled disease represents the biggest danger, there was a shift toward better balancing of the treatment intensity and logistics of administration. With the introduction of COVID-19 vaccines, many of these steps have been rolled back.
The first COVID-19 vaccine was approved on December 11, 2020. Currently there are three Food and Drug Administration emergency use-authorized (EUA) vaccines available against COVID-19 in the United States, with many other vaccine candidates either under investigation or approved and being administered across the world. Clinical trials that led to the approval of these vaccines did not include patients with hematological malignancies, including patients with MM, but the vaccines are believed to be safe in these patients. The efficacy of these vaccines in immunocompromised patients remains unclear, but given the clinical efficacy and immune responses in non-immunocompromised subjects, it is expected that these vaccines will provide some level of protection against SAR-CoV-2 infection. Below are answers to some common questions related to patients with MM, different treatment regimens, and COVID-19 vaccines:
- Which is the preferred vaccine for patients with MM?
- Patients with MM should be counseled to get any vaccine that is available to them. The two current SARS-CoV-2 mRNA vaccines (Pfizer/BioNtech, Moderna) use an mRNA-based approach and do not include a virus. The available viral vector (Adenovirus 23 [Adv]) vaccines (e.g., Johnson and Johnson) do not contain replicating virus and are thus safe in immuncompromised patients. There are no head-to-head trials comparing the efficacy of current EUA vaccines. Based on the safety data, any of the three currently approved vaccines are considered safe and beneficial for patients with MM.
- What are the guidelines for testing anti-SARS-CoV-2 antibody titers after the vaccine administration?
- Routine assessment of anti-spike protein antibody titers post-vaccination is not recommended as antibody responses have not been studied in patients with cancer. There are no antibody titer thresholds that correlate with immunity, and longevity of these responses is also unknown. Such testing, including T-cell assays, should only be done in the context of clinical trials
- Should chemotherapy be held prior to vaccine doses?
- COVID-19 vaccination roll-out differs by state, and access to vaccines is very variable across the United States. Immunological responses to COVID-19 vaccines during chemotherapy cycles is unknown. National Comprehensive Cancer Network guidelines also highlight that granulocytopenia itself does not interfere with vaccine responses. Due to complex treatment regimens and intervals between treatment, patients should be counseled to get vaccines when available, irrespective of the timing of chemotherapy. However, in patients undergoing a stem cell transplantation or chimeric antigen receptor (CAR) T-cell treatment, if vaccination could not be completed before the procedure, it should be deferred to until three months post-treatment.
- How should we counsel vaccinated patients with MM to protect themselves?
- Recently, the Centers for Disease Control and Prevention announced loosened restrictions for fully vaccinated individuals two weeks after finishing their vaccinations. However, patients with MM should continue to practice caution, as the efficacy of these vaccines is unknown in patients with cancer. They should continue to wear face masks, avoid crowds, and maintain social distancing to protect themselves. Studies regarding immunologic responses and revaccination are forthcoming and will provide more insight.
- Are there specific types of treatments that should be avoided?
- Based on the data currently available, there is no specific anti-myeloma treatment that appears to have a distinct effect on the risk of infection, outcome, or response to vaccination.
We encourage all healthcare professionals to engage their patients with MM in conversations regarding the impact this ongoing pandemic is causing on their health and how to better protect themselves, including discussions about COVID-19 vaccines.
Author Bios:
Zainab Shahid, MD, FACP, received her medical degree from Allama Iqbal Medical College in Lahore, Pakistan. Her postdoctoral training included an internal medicine residency at Sinai-Grace Hospital in Detroit and an infectious diseases fellowship at the University of Connecticut. Dr. Shahid is a Fellow of the American College of Physicians, a member of several professional societies, and an active researcher. She is currently serving as principal investigator for COVID-19–focused clinical trials at her institution and a committee member for American Society for Transplantation and Cellular Therapy (ASTCT) COVID Treatment Guidelines committee. She is also one of the authors for the American Society of Hematology-ASTCT COVID-19 vaccines information frequently asked questions.
Dr. Shahid serves as the medical director of Bone Marrow Transplant Infectious Diseases at Levine Cancer Institute/Carolinas Healthcare System and Clinical Associate Professor of Medicine at the University of North Carolina, Chapel Hill.
Shaji K. Kumar, MD, is consultant in the Division of Hematology and Mark and Judy Mullins Professor of Hematological Malignancies at Mayo Clinic in Rochester, Minnesota. He also serves as medical director for the Mayo Clinic Cancer Center Clinical Research Office, Mayo Clinic.
Dr. Kumar received his medical degree from the All India Institute of Medical Sciences in New Delhi, India. His postdoctoral training included a residency in internal medicine from the All India Institute of Medical Sciences, followed by an internal medicine residency and a hematology/oncology fellowship at the Mayo Graduate School of Medicine in Rochester, Minnesota.
Dr. Kumar’s research focuses on the development of novel drugs and drug combinations for the treatment of myeloma. His laboratory focuses on understanding the role of bone marrow microenvironment in the development and progression of myeloma.
Dr. Kumar serves as co-chair of the NCI Myeloma Steering Committee and as chair of the NCCN Multiple Myeloma Guidelines Panel.
References
- Chari A, Samur MK, Martinez-Lopez J, et al. Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set. Blood 2020; 136(26): 3033-40.
- Engelhardt M, Shoumariyeh K, Rosner A, et al. Clinical characteristics and outcome of multiple myeloma patients with concomitant COVID-19 at Comprehensive Cancer Centers in Germany. Haematologica 2020; 105(12): 2872-8.
- Hultcrantz M, Richter J, Rosenbaum C, et al. COVID-19 infections and outcomes in patients with multiple myeloma in New York City: a cohort study from five academic centers. medRxiv 2020.
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