CAR T-cell Therapy Establishes Prominent Role Across Hematologic Malignancies

In recent years, cellular immune therapies such as chimeric antigen receptor (CAR) T-cell therapy have significantly improved response rates for various hematological malignancies. The Multiple Myeloma and Amyloidosis Multidisciplinary Team (MDT), Bone Marrow and Stem Cell Transplant MDT, and the Hematologic Oncology MDT at Barbara Ann Karmanos Cancer Institute in Detroit, Michigan, have helped drive many treatment advancements in cellular immune therapies for cancers.

Karmanos offers all approved CAR T-cell therapies for non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), and multiple myeloma (MM). The institute also continues to support research into new treatment indications for which CAR T-cell therapy could be used. CAR T-cell therapy is at the cutting edge of treatments for certain cancers, wherein the patient’s T cells, an integral part of the immune system, are genetically modified to recognize and kill the cancer cells.

Cancers Show Promising CAR T Response Rates

The outcomes of CAR T-cell therapies have been remarkable, especially because most patients receiving this immunotherapy have faced difficulties in controlling their disease despite multiple rounds of chemotherapy. The Karmanos team collaborated with leading cancer centers around the country on various pivotal clinical trials leading to the FDA approval of CAR T-cell therapy.

The complete response rates for ALL are approximately 60% to 70%.^1,2 Regarding NHL, the FDA has approved CAR T-cell therapy to treat diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma and transformed lymphoma. Patients with these diseases must meet specific requirements to receive CAR T-cell therapy including that their cancer does not respond to initial chemotherapy and relapses within 1 year or there is relapse after 2 previous lines of chemotherapy.

The long-term complete response rates in patients with DLBCL in the third-line setting are around 40% to 50%.^3-5 For patients with DLBCL whose disease does not respond to initial therapy or relapses within 1 year of completing treatment, CAR T-cell therapy significantly improved the chance of being cured compared with standard salvage chemotherapy.^6,7

With CAR T-cell therapy, we can also target mantle cell lymphoma. For this disease, we have seen a complete response in two-thirds of patients whose disease had relapsed or not responded to multiple chemotherapy regimens.⁸ CAR T-cell therapy also showed very high response rates in patients with follicular lymphoma whose disease had relapsed after 2 prior lines of chemotherapy.^9,10 The response rate for patients with MM whose disease relapsed after 4 or more prior lines of chemotherapy was 80% to 95% after CAR T-cell therapy treatment.^11,12

Possible Adverse Effects

Some patients may develop unique adverse effects (AEs) that should be monitored closely for the first few weeks after infusion. AEs include cytokine release syndrome (CRS), which may manifest as high fever, low blood pressure, low oxygenation, neurological toxicity, confusion, word-finding difficulty, and rare cases of seizure or coma. The most severe AEs usually occur within the first couple of weeks after infusion of CAR T cells. Patients can also be at risk for low blood counts and a weakened immune system. If this happens, the patient may need antimicrobial treatments to prevent severe infection.

Ongoing CAR T-cell Therapy Research

In the recent years, research has also focused on strategies to reduce the AEs of this unique therapy. Karmanos participated in a clinical trial in which patients with DLBCL received steroids for 3 days at the time of infusion of CAR T-cell therapy, which led to less risk of CRS without compromising efficacy of the treatment.¹³ This approach is now used for patients at a high risk of developing severe AEs from CAR T-cell therapy.

We have an ongoing clinical trial in which we give an antibody treatment to patients undergoing CAR T-cell therapy, which may help reduce risk of related neurological toxicity. Our team is also participating in clinical trials investigating allogeneic CAR T cells. With this treatment, patients receive genetically modified CAR T cells from a donor. This method may hasten therapy compared with waiting on the patient’s manufactured immune cells. We are also collaborating with Karmanos experts specializing in solid tumor oncology for clinical trials with CAR T-cell therapy. These trials involve other cellular treatments for breast, lung, prostate, head and neck, and gynecologic cancers.

Karmanos specialists have experience in providing commercially approved and investigational cellular therapies. As a National Cancer Institute–Designated Comprehensive Cancer Center, we work closely with investigators developing novel strategies to make this therapy safer, develop pathways toward new indications, and ensure more accessibility to CAR T-cell therapy. With our robust clinical trials program and experienced team, we are committed to further improving outcomes for patients who are candidates for these therapies and to overcoming challenges associated with them.

Abhinav Deol, MD, is a medical oncologist and member of multidisciplinary teams including Bone Marrow & Stem Cell Transplant, Hematology Oncology, and Multiple Myeloma and Amyloidosis at Karmanos Cancer Institute in Detroit, Michigan.

References

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