Community medical centers can safely administer CAR-T, but extensive preparation required
Click Here to Manage Email Alerts
Key takeaways:
- Liso-cel efficacy appeared comparable for patients with large B-cell lymphoma treated at community sites and those treated in trials.
- Adverse events also appeared similar.
Chimeric antigen receptor T-cell therapy can be administered at community centers and on an outpatient basis with proper preparation, education and resources, according to prospective study results.
Adults with relapsed or refractory large B-cell lymphoma (LBCL) treated with lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb) at community sites had similar outcomes and adverse events as those who participated in the TRANSCEND-NHL-001 trial, which led to the drug’s FDA approval in 2021.
The findings may allow more individuals to access CAR-T, researchers concluded.
“Overall, the safety and the [efficacy of the] trial were excellent, and both outpatients and inpatients did well,” study author Yuliya P.L. Linhares, MD, chief of lymphoma services at Miami Cancer Institute, told Healio. “There’s probably going to be motion toward administration in more community centers, but I don’t think that most centers will be equipped to take care of these patients in the near future.”
Background
Lisocabtagene maraleucel, often called liso-cel, is a CD19-directed CAR-T that has been approved for second-line treatment of LBCL, among other indications.
CAR-T administration requires a multidisciplinary team that can manage adverse events unique to immunotherapy, such as cytokine release syndrome and neurotoxicity. Consequently, administration historically has been limited to university-affiliated medical centers, Linhares said.
However, approximately 70% of patients with relapsed or refractory LBCL are treated at local medical sites, according to study background.
“Greater availability of CAR T cells would potentially decrease health care costs and improve outcomes,” Linhares said.
Methods
Researchers conducted the multicenter phase 2 OUTREACH trial to evaluate the capability of community medical centers to administer CAR-T.
They defined community sites as “nontertiary care centers not associated with a university” that may or may not have Foundation for the Accreditation of Cellular Therapy (FACT) accreditation.
In order to monitor CAR-T recipients on the outpatient basis, community centers were required to have hematopoietic stem cell transplantation or phase 1 study capabilities, standard operating procedures for outpatient monitoring and admission, and a dedicated multidisciplinary medical team.
The analysis included 18 sites that treated 82 patients (median age, 66 years; range 28-86; 66% men; 84% white) with relapsed or refractory LBCL who had received at least two prior lines of therapy. Patients received leukapheresis, lymphodepleting chemotherapy and liso-cel.
The majority (70%) of patients received CAR-T as outpatients.
Incidence of grade 3 or higher adverse events served as the primary endpoint. Efficacy served as the secondary endpoint.
Results
Of the participating sites, 72% had not previously administered CAR-T, 44% did not have FACT accreditation and 56% were oncology clinics with separate associated hospitals (dual entity).
About one-third (32%) of participants received treatment at CAR-T naive sites, 37% underwent treatment at non-FACT centers and 48% received treatment at dual entity locations.
Grade 3 or worse adverse events occurred at similar rates among adults who had outpatient vs. inpatient treatment (74% vs. 76%). No grade 5 adverse events occurred.
About half (49%) of participants developed CRS, neurotoxicity or both.
Patients in OUTREACH had similar rates as those in the TRANSCEND trial of grade 3 or worse CRS (0% vs. 2%) and neurotoxicity (10% each).
Adults treated on an outpatient basis had slightly lower rates of CRS as those treated on an inpatient basis (37% vs. 48%). Neurotoxicity rates appeared comparable (overall, 28% vs. 32%; grade 3 or higher, 12% vs. 4%).
One-quarter (25%) of patients treated as outpatients never required hospitalization. Among those who did, median time to hospitalization was 5 days (range, 2-310) and the median duration of hospital stay was 6 days (range 1-28).
Results showed similar objective response rates (80% vs. 73%) and complete response rates (54% vs. 53%) in OUTREACH vs. TRANSCEND.
Start preparing now
Improved access to CAR-T already has had a dramatic impact on LBCL treatment.
“We have third-line clinical trials, and we’re struggling to accrue [participants] because we have fewer patients who even would need third-line or fourth-line therapy,” Linhares said. “That’s a very good indicator that higher CAR T cell availability and faster access is saving more lives.”
However, despite positive results from OUTREACH, further expansion into community medical centers is not imminent.
“Less than 50% of centers are ready for CAR-T,” Linhares said.
Participating sites require extensive training and access to tocilizumab (Actemra, Genentech) to manage toxicities, she said.
“The hematology team had to be trained on the protocol,” Linhares said. “Then I had to do training for our advanced practice provider team, and separate training for the CAR T cell side effects. We had these materials easily available for our on-call team day and night, and I was available at all times as a principal investigator on this trial.
“Beyond the official part — the nursing training — we did a lot of unofficial education,” Linhares added. “For example, we had our infectious disease doctor give an educational lecture specifically on CAR-T associated infectious disease complications and management. I did a lecture to our pulmonary and critical care physicians, and ED physicians were invited to educate on the biology of this treatment and complications.”
Community sites need a variety of resources to administer CAR-T, Linhares said. These include an infusion center with trained nurses, a readily available advanced practice provider team, a 24/7 answering service, experienced pharmacists, access to tocilizumab, infectious disease consultants and strong social work.
“In general, we have staff shortages in community centers,” Linhares added. “You may have a lot of nurses who are temporary nurses or nurses with minimal experience. Physician expertise is important, but this cannot be done without experience and expertise of a physician assistant team and nursing.”
It also takes time for medical centers to establish contracts and reimbursements for CAR-T, she said.
“I would encourage community centers that do have these multidisciplinary teams to get on the road of educating their centers and starting contracts with the vendors for CAR T cell administration,” Linhares said. “These are the therapies that are here to stay, and I think that the pool of eligible candidates will only grow because these therapies will be moved closer to the first line of treatment. It’s inevitable. I encourage the centers to reach out, if needed, to other community centers who participated in this trial to share their expertise.”
For more information:
Yuliya P.L. Linhares, MD, can be reached at yuliyal@baptisthealth.net.
Collapse
Click Here to Manage Email Alerts