Cell therapy amid COVID-19: New anxieties and lessons learned
Patients on track to receive chimeric antigen receptor T-cell therapy typically have run out of time and options.
For many of these patients, a delay of a week or more can result in disease that has advanced beyond the ability to treat successfully.
Despite their dire status, patients looking to undergo CAR T-cell therapy during the COVID-19 pandemic have faced an array of challenges.
However, Cell Therapy Next discovered that the community of health care professionals tasked with delivering these potentially lifesaving therapies across the United States has adapted to life under COVID-19 restrictions, ensuring patients receive treatment wherever possible — an approach that could translate to more efficient treatment in the future.
Stories from the Front
The battle against COVID-19 is taking place across thousands of fronts in the U.S., from underfunded rural regional hospitals to the steel and glass high-rises of well-endowed university centers.
What becomes clear when speaking with clinicians across the nation is that the effect of the pandemic on the delivery of CAR T-cell therapy depends on the type of center that provides it, as well as its location.
There were some initial delays providing CAR T-cell treatments at Mayo Clinic in Rochester, Minnesota, but they were short-lived and imposed in the name of patient safety as the institution looked to acquire an accurate diagnostic test to determine which patients had COVID-19.
Access to an accurate COVID-19 test was “extremely limited,” according to Yi Lin, MD, PhD, associate professor of medicine and chair of the cell therapy cross-disciplinary group at Mayo Clinic Cancer Center. This left Mayo Clinic unable to test asymptomatic patients as a screening measure before CAR T-cell treatment.
“The Mayo Clinic labs worked around the clock to increase production of a test, and within weeks we had sufficient testing capabilities to screen all patients prior to cell collection for CAR-T manufacturing and prior to CAR-T treatment,” she told Cell Therapy Next.
Mayo Clinic in Rochester has not been overwhelmed by patients with COVID-19 and there has been no need to redeploy cell therapy clinicians to fight the pandemic, Lin added.
She noted that FDA-approved CAR T-cell therapy is for patients with aggressive acute leukemia and lymphoma whose disease has not responded to other conventional therapies; thus, postponing treatment is not an option.
“These patients cannot wait until after the COVID-19 pandemic to receive CAR T-cell therapy,” Lin said. “Because we have not seen the surge in COVID-19 cases that has overwhelmed other hospitals, we have been able to treat CAR-T patients without delay.”
Dana-Farber Cancer Institute in Boston continues to provide CAR T-cell treatments and consultations despite social distancing measures.
Of course, it is not business as usual for the cell therapy clinic, which has adapted to provide services.
But Kathleen McDermott, RN, BSN, OCN, BMTCN, CAR-T and transplant nurse navigator at Dana-Farber, noted that in some cases, patients themselves are delaying treatment.
“Patients are understandably hesitant and fearful to proceed to CAR-T treatment in the current environment,” she told Cell Therapy Next. “Several have decided to continue with salvage therapy locally, hoping to maintain disease control and revisit CAR-T at a later date.”
Restrictions on family visitors and caregivers present another obstacle for employees at the clinic, McDermott added.
Once checked in, patients undergoing CAR T-cell therapy must endure the weekslong process with only an electronic device at most to keep them connected to friends and loved ones.
“The lack of the physical presence and support of family caregivers has also placed the additional burden on health care workers of needing to be a caregiver substitute,” McDermott said. “The COVID-19 pandemic has added a new dimension of stress, anxiety and worry for patients, families and health care workers.”
Patients remain worried about exposure to COVID-19, which has led to a decrease in new patient volume at Moffitt Cancer Center, according to Frederick L. Locke, MD, medical oncologist and translational researcher in the department of blood and marrow transplant and cellular immunotherapy at Moffitt, and member of the Cell Therapy Next Peer Perspective Board.
Moffitt, a standalone center in Florida dedicated to cancer care, must take steps to ensure patients are tested for COVID-19 before the CAR-T process, as well as to limit transmission of the virus that causes it.
Locke confirmed that Moffitt’s CAR T-cell therapy program has been open for business during the pandemic.
“We haven’t been tasked thus far to help with overflow care of patients with COVID-19; therefore, we are able to focus our care on patients with cancer,” Locke told Cell Therapy Next. “Our center is the best place a patient can be right now because of our diligence when it comes to patient safety and preventing the spread of the disease.”
To address volume decreases resulting from the COVID-19 restrictions, some patients have been converted to virtual telehealth visits, Locke said.
Locke said he understands why patients would be worried about in-clinic visits, as well as the travel and potential exposure associated with initial consultations.
However, he noted that patients considering CAR T-cell therapy usually are seeking a treatment of last resort.
“Because of that, we continue to offer CAR T-cell therapy, both for standard-of-care patients and for those receiving CAR-T as part of interventional clinical trials,” he said.
In New York City, the epicenter of the COVID-19 outbreak, many nurses and physicians have been deployed within the Mount Sinai system to deal with emergency needs, according to Karyn Aalami Goodman, MD, MS, professor and vice chair for research and quality in the department of radiation oncology at Icahn School of Medicine at Mount Sinai, and associate director for clinical research at Tisch Cancer Institute.
She spoke with Cell Therapy Next near the height of the pandemic in New York and confirmed that overall cancer care services had been severely reduced, including administration of CAR T-cell therapies.
In mid-April, Goodman said overall volume for infusions and radiation therapies had declined by about 80% from normal, but that they had witnessed a plateau in COVID-19 cases and were looking for ways to resume services.
“Now, our major focus is going back and examining those patients we had to delay, in addition to reopening our research, surgical and other programs, and doing so in as safe a way as possible,” Goodman said.
The challenge of treating patients who require CAR T cells is that many of them have failed numerous other forms of therapy, according to Joseph Alvarnas, MD, clinical professor in the department of hematology and hematopoietic cell transplantation at City of Hope.
“This means they are in a situation where time is of the essence or, alternatively, they are on a sequence of therapy that cannot be interrupted,” he told Cell Therapy Next.
“We’ve all heard stories about rescheduling and delays in care in the media, but patients like these can’t be delayed and they can’t be rescheduled,” Alvarnas added. “It requires that we respect the needs of these patients to ensure their continuity of care.”
Planning for the COVID-19 Counterattack
City of Hope, near Los Angeles, is a dedicated cancer center. As such, COVID-19 has not impacted its ability to provide timely CAR T-cell treatments.
“Patients scheduled to receive commercial CAR T-cell products continue to do so without delay,” Alvarnas told Cell Therapy Next.
“The key is creating a safe environment,” he added. “We have very robust infection control policies for both facilities and the people who move within them.”
These policies were in place before the COVID-19 pandemic, he pointed out, because “individuals who have conditions that might require CAR T-cell therapy are severely immunocompromised.”
Mayo Clinic has established its own COVID-19 task force, and Lin said her department has communicated with both the task force and the facility’s pharmacy to secure sufficient supplies of cytokine blockade drugs — such as tocilizumab (Actemra, Genentech) and sarilumab (Kevzara; Sanofi Genzyme, Regeneron) — for patients receiving CAR T-cell therapy. They also obtained excess supply for off-label compassionate use by patients with COVID-19.
Securing an ample amount of pharmacy supplies and disinfected spaces are among many actions centers that deliver CAR T-cell therapies must contemplate during a pandemic.
The CAR T-Cell Consortium comprises a group of investigators from eight U.S. academic institutions formed to pool resources for the evaluation and optimization of cellular therapy.
The consortium recommends centers that provide these therapies consider a range of possible pandemic impacts, including on apheresis and cell processing, staffing, shipping and housing.
The group published an opinion document in Biology of Blood and Marrow Transplantation that addressed several key areas to consider when providing CAR T-cell therapy during the COVID-19 pandemic (see box).
“We assembled a group of experienced CAR-T clinicians to lay out best practices in terms of selecting appropriate patients, performing timely and relevant screening for COVID-19, and managing patients during and after their [CAR T-cell therapy] during the COVID-19 pandemic — and to express our opinion that for many patients, CAR T cells offer potentially lifesaving therapy,” David L. Porter, MD, director of cell therapy and transplantation at Abramson Cancer Center at University of Pennsylvania and a member of the CAR T-Cell Consortium, told Cell Therapy Next. “As such, patients should continue to receive therapy when appropriate as safely as possible.”
Referrals for CAR T-cell therapy should continue amid pandemic restrictions, and the consortium recommends all patients scheduled to undergo CAR T-cell infusions be tested for COVID-19 before they start lymphodepletion chemotherapy, Porter said.
“Appropriate patients should continue to be referred for CAR T cells,” he said. “The group also recommends that therapy should be delayed if patients exhibit any signs of COVID-19 infection, because the virus can exacerbate symptoms of cytokine release syndrome [CRS] that accompany CAR T-cell infusions.
“However, patients who are at more risk for dying of their disease without effective treatment should still be evaluated and offered CAR T cells,” Porter concluded.
The consortium aimed to give centers that offer CAR T-cell therapy guidance on how to continue providing the therapies in a safe manner while being mindful of the potential for constraints on resources, Peter A. Riedell, MD, assistant professor of medicine and director of clinical research for the hematopoietic cellular therapy program at The University of Chicago and fellow consortium member, told Cell Therapy Next.
Riedell said COVID-19 has had an impact on the delivery of CAR T-cell therapy at his institution. New referrals from community oncologists have slowed and concerns have been raised about getting patients to and from the centers that perform CAR-T, many of which are in major metropolitan centers.
“Patients may be wary of coming for even the initial consultation, and this has resulted in a significant decline in the number of referrals we have seen since the start of the COVID-19 pandemic,” he said.
Nevertheless, Riedell said his center continues to provide CAR T-cell treatments and follow-up care. What has changed is the timing of treatments, to ensure enough resources are available to care for patients after they receive their infusions.
Some Things Will Never Be the Same
There is little doubt the COVID-19 pandemic represents a transformative moment for public health. However, only time will tell which practices implemented to deliver health care services during this initial outbreak will remain common going forward.
Alvarnas takes a positive view regarding the overall impact of COVID-19 on health care and CAR T-cell delivery.
“It will drive innovation in delivery of cancer care and create a more robust and uniform approach to the care of immunocompromised patients throughout the health care system,” he predicted.
The role of telehealth and virtual visits, often referred to as a pandemic necessity, likely will continue to expand, experts said.
“In the CAR-T space, I hope the use of telehealth will allow us to have initial consultations that previously we may not have considered, because of issues such as distance,” Locke said. “I’m hopeful that telehealth visits will help us bring in patients we might not otherwise see and, in the process, save more lives.”
Riedell also sees a role for telehealth in the consultation process but said it may be even more valuable for the long-term follow-up required for patients who receive CAR T cells.
Riedell cited the work of The University of Chicago’s mobile phlebotomy unit as an example of the innovation required to accommodate patients who face pandemic restrictions. The unit is dispatched to patients’ homes to collect samples for lab analysis back at the center.
“It’s been beneficial to patients and allows clinicians to keep a close eye on our patients after they receive CAR T-cell therapy,” Riedell said. “As we emerge from this COVID-19 crisis, I think that patients will expect that this is still an option.”
Mayo Clinic’s Lin said her center implemented remote monitoring technologies and virtual visits before the COVID-19 pandemic, but that the response likely will accelerate their use. For example, Mayo Clinic’s Connected Care Program has successfully implemented remote monitoring for patients with chronic diseases, such as diabetes and congestive heart failure.
“We’ve demonstrated how this technology improves patient compliance in their medical management at home,” Lin said. She said it also allows for more efficient use of face-to-face clinic visits, improves clinical outcomes and helps patients feel more engaged with their clinical team.
“This is a priority for us to adapt during and after COVID-19 to enhance the safe monitoring of our patients in the outpatient setting,” she added. “We anticipate that the virtual visits for patients who live far from Mayo will likely continue even after the pandemic to improve the patient the care they receive at Mayo.”
Perhaps the most important lesson for clinicians from the COVID-19 experience is that they must remain flexible and up to date on the latest information to provide the highest quality of care in the safest manner possible.
“CAR-T treatment is already logistically challenging,” Lin said, adding that management of patients during pandemic has added even more complexity.
“Keeping a real-time pulse on current and evolving health care resources is important to anticipate needs and safely get each patient through treatment,” she said.
One important takeaway from the experience, according to Locke, is that planning before a crisis is the keystone of an effective response. Perhaps even more important, he added, is learning from the response to transform how health care and CAR T-cell treatments are delivered going forward.
“A lot of the plans and accommodations we have put into effect to confront the pandemic will be with us as we go into the future,” Locke said. “We should be very aggressive about trying to seize this moment to redefine cancer care.” – by Drew Amorosi
- Bachanova V, et al. Biol Blood Marrow Transplant. 2020;doi:10.1016/j.bbmt.2020.04.008.
- For more information:
- Joseph Alvarnas, MD, can be reached at firstname.lastname@example.org.
- Karyn Aalami Goodman, MD, MS, can be reached at email@example.com.
- Yi Lin, MD, PhD, can be reached at firstname.lastname@example.org.
- Frederick L. Locke, MD, can be reached at email@example.com.
- Kathleen McDermott, RN, BSN, OCN, BMTCN, can be reached at firstname.lastname@example.org.
- David L. Porter, MD, can be reached at email@example.com.
- Peter A. Riedell, MD, can be reached at firstname.lastname@example.org.
Disclosures: Lin reports research funding to her institution from bluebird bio, Bristol-Myers Squibb, Janssen, Kite/Gilead, Merck and Takeda, and advisory board roles with bluebird bio, Bristol-Myers Squibb, Celgene, Gamida Cells, Janssen, Juno, Kite/Gilead, Legend and Novartis. Locke reports scientific advisory roles with Allogene, Bristol-Myers Squibb/Celgene, Caliber, Cellular Biomedicine Group, Gamma Delta Therapeutics, Kite/Gilead, Novartis and Wugen; a consultant role with Cellular Biomedicine Group; research support from Kite/Gilead; and patents related to CAR T-cell therapy through his work at Moffitt Cancer Center. Porter reports consultant/advisory roles with Gerson Lehrman Group, Glenmark, Incyte, Janssen, Kite/Gilead and Novartis; research funding from Novartis; and a patent as inventor for CTL019. Riedell reports research funding from Juno Therapeutics, Kite/Gilead and Novartis; a consultant role with Novartis; a speakers bureau role with Kite/Gilead; and advisory board roles with Celgene/Bristol-Myers Squibb and Novartis. Alvarnas and McDermott report no relevant financial disclosures.