In Practice

The Handoff: Transferring CAR T Patients Back to the Community Setting

In this installment of In Practice, Julio C. Chavez, MD, assistant member in the lymphoma section of the department of malignant hematology at Moffitt Cancer Center, will discuss the challenges and best practices when preparing patients and their community oncologist for departure from the cell therapy clinic and back to the community setting.

As Chavez explains, although most toxicities occur within the first 30 days after CAR T-cell therapy, while the patient is under the care of the cell therapy clinic, there are important post-treatment issues to consider when returning to the community setting. Many community-based oncologists are unfamiliar with the toxicities and care needs of this novel treatment form, making communication between the community oncologist and cell therapy clinic a key issue in post-treatment care.

Julio C. Chavez, MD
Julio C. Chavez

We look forward to your input on topics for future installments of In Practice and encourage our readers to submit their ideas. If there is a practical concern you would like addressed, please email us at CellTherapyNext@healio.com.

Q: What are some of the key issues you face when transferring patients who receive CAR T-cell therapy back to their community oncologist?

Follow-up timeline

CAR T-cell therapy represents a novel approach to treat cancers using the patient’s immune system cells. This therapy has a unique side-effect profile caused by the activation of cytokines and other immune system cells that lead to cytokine release syndrome and neurotoxicity. Due to the potential severity of these toxicities, this treatment is limited to academic centers with experience in CAR T-cell therapy, cell therapy and management of these specific toxicities. Thus, there has been little opportunity for community oncologists to have handoff experience managing these patients receiving this therapy; there is a significant degree of unfamiliarity with the potential residual toxicities and follow-up care.

Another issue is the coordination of care. There must be an open and smooth channel of communication with the community oncologist to provide an appropriate transition of care to patients in the post-CAR T-cell therapy phase. Adequate documentation of the treatment and follow-up plan is important, as well as providing complete medical records to the primary oncologist. In my experience, the best approach is a personal conversation with the local oncologist. Using other alternatives, such as email, is also a good approach.

Q: How does post-treatment management for CAR T-cell therapy differ from post-transplant care?

Post-CAR T-cell therapy management is different from what we do for patients who have allogeneic hematopoietic transplant (allo-HCT). However, it has similarities with the care of patients after they have autologous hematopoietic transplant (auto-HCT).

One of the key issues with allo-HCT is the management of immunosuppression and graft-versus-host disease that requires constant monitoring and evaluation by the transplant physician. Patients with active GVHD may still need to be followed in the academic center several months after the transplant. Similar to patients who have auto-HCT, there are still post-procedure issues, such as cytopenias, immunosuppression (hypogammaglobulinemia) and physical deconditioning.

Q: Do you follow any established professional guidelines for the transfer process, after the patient is discharged from CAR T-cell therapy?

We do not have any standard guidelines because the needs for every patient are different. What we typically do is to give a signout of a patient’s active problems after CAR T-cell infusion. There are patients who will still need transfusion of blood products, growth factors, IV antibiotics or immunoglobulins. Some patients may also need reconditioning and physical therapy (inpatient or outpatient).

Q: What are the most common warning signs of CAR T-cell therapy toxicity that should be discussed with patients before transfer back to the community setting?

Patients have to stay closer to the cell therapy center for the first 30 days after CAR T-cell infusion. Once they are discharged, patients are educated about potential issues that could happen once they are back in the community setting, such as recurrent infections (due to cytopenias, T-cell dysfunction or hypogammaglobulinemia). We tell patients that transfusion of blood products may be needed. Late infections and monitoring of fevers and related symptoms will be important. We also explain to them about potential signs of clinical relapse (new adenopathy, persistent pain or B symptoms).

Q: In the case of relapse after CAR T-cell therapy, what is the protocol for treatment? Does the patient remain in community oncology care or return for further consideration to the cell therapy unit?

Follow-up care

Unfortunately, there is no standard treatment for patients with diffuse large B-cell lymphoma or B-cell acute lymphoblastic leukemia who relapse after CAR T-cell therapy and they are considered to have a poor prognosis. Many centers treat this situation differently, based on available options, including clinical trials.

What I typically recommend is to consider clinical trials that can be available in the CAR T-cell center or cancer center where the patient received this therapy. Some community practices are also involved in clinical trials with novel oral agents or monoclonal antibodies and should also be considered. I always support a discussion between the primary oncologist and CAR T-cell physician for treatment options if this situation occurs. Referral to hematology or lymphoma or leukemia clinics is essential for the discussion of treatment options.

Q: What should the long-term care strategy be for community oncologist after their CAR T-cell patients have been treated?

The strategy will differ depending on the patient’s status. The majority of patients recover enough after 30 days post-CAR T-cell therapy and there likely is no need for complex intervention by the local oncologist. Some patients will still have cytopenias or important deconditioning and in these cases, significant involvement by the community oncologist is important. Transfusion of blood products or administration of growth factors may be needed. Adequate management of patients in rehabilitation facilities could be needed and coordination of care with a rehabilitation medicine physician or hospitalist will be necessary.

For patients who are fully recovered and in remission, we usually follow-up using the standard monitoring of patients with lymphoma or leukemia. For example, in lymphomas we usually follow-up patients using the NCCN guidelines for lymphoma care, with follow-ups every 3 months for the first 1 to 2 years, then every 6 months.

CAR T-cell products using retroviral and lentiviral vectors have the potential risk for malignant transformation due to generation of replication-competent virus or incidental insertional mutagenesis in normal T cells or other cells. Therefore, the FDA has mandated a long-term follow up to 15 years to monitor these potential effects.

Q: What else do you want community oncologists and other physicians to know about post-CAR T-cell treatment monitoring?

Some patients can still be part of clinical trials and specific monitoring may be needed, such as CAR T-cell persistence or other biomarkers that — in some instances — are related to disease recurrence. Patients in clinical trials are also mandated to be followed-up for 15 years (long-term follow-up) due to the risk for malignant transformation.

Disclosures: Chavez reports participating in advisory boards or speakers bureaus for Kite, Genentech, Novartis, Bayer, and Janssen, and has received research support from Merck.

In this installment of In Practice, Julio C. Chavez, MD, assistant member in the lymphoma section of the department of malignant hematology at Moffitt Cancer Center, will discuss the challenges and best practices when preparing patients and their community oncologist for departure from the cell therapy clinic and back to the community setting.

As Chavez explains, although most toxicities occur within the first 30 days after CAR T-cell therapy, while the patient is under the care of the cell therapy clinic, there are important post-treatment issues to consider when returning to the community setting. Many community-based oncologists are unfamiliar with the toxicities and care needs of this novel treatment form, making communication between the community oncologist and cell therapy clinic a key issue in post-treatment care.

Julio C. Chavez, MD
Julio C. Chavez

We look forward to your input on topics for future installments of In Practice and encourage our readers to submit their ideas. If there is a practical concern you would like addressed, please email us at CellTherapyNext@healio.com.

Q: What are some of the key issues you face when transferring patients who receive CAR T-cell therapy back to their community oncologist?

Follow-up timeline

CAR T-cell therapy represents a novel approach to treat cancers using the patient’s immune system cells. This therapy has a unique side-effect profile caused by the activation of cytokines and other immune system cells that lead to cytokine release syndrome and neurotoxicity. Due to the potential severity of these toxicities, this treatment is limited to academic centers with experience in CAR T-cell therapy, cell therapy and management of these specific toxicities. Thus, there has been little opportunity for community oncologists to have handoff experience managing these patients receiving this therapy; there is a significant degree of unfamiliarity with the potential residual toxicities and follow-up care.

Another issue is the coordination of care. There must be an open and smooth channel of communication with the community oncologist to provide an appropriate transition of care to patients in the post-CAR T-cell therapy phase. Adequate documentation of the treatment and follow-up plan is important, as well as providing complete medical records to the primary oncologist. In my experience, the best approach is a personal conversation with the local oncologist. Using other alternatives, such as email, is also a good approach.

Q: How does post-treatment management for CAR T-cell therapy differ from post-transplant care?

Post-CAR T-cell therapy management is different from what we do for patients who have allogeneic hematopoietic transplant (allo-HCT). However, it has similarities with the care of patients after they have autologous hematopoietic transplant (auto-HCT).

PAGE BREAK

One of the key issues with allo-HCT is the management of immunosuppression and graft-versus-host disease that requires constant monitoring and evaluation by the transplant physician. Patients with active GVHD may still need to be followed in the academic center several months after the transplant. Similar to patients who have auto-HCT, there are still post-procedure issues, such as cytopenias, immunosuppression (hypogammaglobulinemia) and physical deconditioning.

Q: Do you follow any established professional guidelines for the transfer process, after the patient is discharged from CAR T-cell therapy?

We do not have any standard guidelines because the needs for every patient are different. What we typically do is to give a signout of a patient’s active problems after CAR T-cell infusion. There are patients who will still need transfusion of blood products, growth factors, IV antibiotics or immunoglobulins. Some patients may also need reconditioning and physical therapy (inpatient or outpatient).

Q: What are the most common warning signs of CAR T-cell therapy toxicity that should be discussed with patients before transfer back to the community setting?

Patients have to stay closer to the cell therapy center for the first 30 days after CAR T-cell infusion. Once they are discharged, patients are educated about potential issues that could happen once they are back in the community setting, such as recurrent infections (due to cytopenias, T-cell dysfunction or hypogammaglobulinemia). We tell patients that transfusion of blood products may be needed. Late infections and monitoring of fevers and related symptoms will be important. We also explain to them about potential signs of clinical relapse (new adenopathy, persistent pain or B symptoms).

Q: In the case of relapse after CAR T-cell therapy, what is the protocol for treatment? Does the patient remain in community oncology care or return for further consideration to the cell therapy unit?

Follow-up care

Unfortunately, there is no standard treatment for patients with diffuse large B-cell lymphoma or B-cell acute lymphoblastic leukemia who relapse after CAR T-cell therapy and they are considered to have a poor prognosis. Many centers treat this situation differently, based on available options, including clinical trials.

What I typically recommend is to consider clinical trials that can be available in the CAR T-cell center or cancer center where the patient received this therapy. Some community practices are also involved in clinical trials with novel oral agents or monoclonal antibodies and should also be considered. I always support a discussion between the primary oncologist and CAR T-cell physician for treatment options if this situation occurs. Referral to hematology or lymphoma or leukemia clinics is essential for the discussion of treatment options.

PAGE BREAK

Q: What should the long-term care strategy be for community oncologist after their CAR T-cell patients have been treated?

The strategy will differ depending on the patient’s status. The majority of patients recover enough after 30 days post-CAR T-cell therapy and there likely is no need for complex intervention by the local oncologist. Some patients will still have cytopenias or important deconditioning and in these cases, significant involvement by the community oncologist is important. Transfusion of blood products or administration of growth factors may be needed. Adequate management of patients in rehabilitation facilities could be needed and coordination of care with a rehabilitation medicine physician or hospitalist will be necessary.

For patients who are fully recovered and in remission, we usually follow-up using the standard monitoring of patients with lymphoma or leukemia. For example, in lymphomas we usually follow-up patients using the NCCN guidelines for lymphoma care, with follow-ups every 3 months for the first 1 to 2 years, then every 6 months.

CAR T-cell products using retroviral and lentiviral vectors have the potential risk for malignant transformation due to generation of replication-competent virus or incidental insertional mutagenesis in normal T cells or other cells. Therefore, the FDA has mandated a long-term follow up to 15 years to monitor these potential effects.

Q: What else do you want community oncologists and other physicians to know about post-CAR T-cell treatment monitoring?

Some patients can still be part of clinical trials and specific monitoring may be needed, such as CAR T-cell persistence or other biomarkers that — in some instances — are related to disease recurrence. Patients in clinical trials are also mandated to be followed-up for 15 years (long-term follow-up) due to the risk for malignant transformation.

Disclosures: Chavez reports participating in advisory boards or speakers bureaus for Kite, Genentech, Novartis, Bayer, and Janssen, and has received research support from Merck.

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