Dr. Joseph Maakaron, a physician with the Blood and Marrow Transplant, Leukemia and Immunotherapy Program at Northside Hospital, recently shared an overview of where immunotherapies stand today in treating hematological malignancies — cancers that begin in the blood, bone marrow or lymph nodes. His talk highlighted how far the field has come and where it is heading.
How treatment used to look
Dr. Maakaron explained that, before 2017, treatment options for aggressive lymphomas such as diffuse large B-cell lymphoma (DLBCL) were limited. About two-thirds of patients were cured with standard chemotherapy, but for those who relapsed, outcomes were poor. Physicians would try salvage chemotherapy and, if possible, a stem cell transplant. Still, for many patients, survival was measured in months.
“This was pretty dismal,” Dr. Maakaron said.
The impact of CAR T-cell therapy
That picture began to change with the introduction of chimeric antigen receptor T-cell therapy — or CAR T. In this treatment, a patient’s own T cells are collected, engineered in a lab to better recognize and fight cancer, and then reinfused after chemotherapy.
While the process is complex, the results have been dramatic. In early studies such as ZUMA-1, patients with relapsed lymphoma achieved much better survival rates. At five years, about 40 percent were still alive — something rarely seen before CAR T.
Follow-up studies like ZUMA-7 showed that CAR T was more effective than the prior standard of chemotherapy and transplant for patients whose lymphoma came back within 12 months. Today, CAR T is the new standard second-line therapy for these patients.
“This is really quite revolutionary when you think about it,” Dr. Maakaron said.
Challenges and new directions
The CAR T process involves several steps: collecting cells, sending them for engineering, waiting for them to be manufactured, then preparing the patient with chemotherapy before infusion. On average, this takes about two months. For patients with aggressive disease, that can feel like a very long time.
“Time is of the essence,” Dr. Maakaron said. “The clock starts ticking whenever you think about CAR T.”
Because of this, researchers are exploring allogeneic CAR T — products made from healthy donor cells that are available “off the shelf.” These therapies could eliminate delays, offer more consistency and even provide longer-lasting results. Early trials show they may be both safe and effective, with manageable side effects.
Overcoming resistance
Not every patient responds to CAR T, and some may relapse. Dr. Maakaron explained that sometimes the engineered T cells do not expand well, do not persist long enough, or become exhausted. In other cases, the cancer cells change and stop expressing the targets that CAR T recognizes.
To address these issues, researchers are developing:
- Dual-target CAR T, which attacks cancer through two different markers.
- PD-1 knockout CAR T, which are less likely to be “turned off” by cancer cells.
- Memory-like CAR T, which may last longer in the body and continue surveillance against relapse.
“These are exciting steps forward,” Dr. Maakaron said.
Beyond blood cancers
Dr. Maakaron also described how cell therapies are expanding beyond blood cancers. One example is tumor-infiltrating lymphocyte (TIL) therapy for melanoma. In this treatment, immune cells already present in a tumor are collected, expanded in the lab, and reinfused.
In clinical trials, about 30 percent of patients with advanced melanoma — who had few other options left — responded to TIL therapy. Some responses have lasted for years. The FDA has approved this therapy for certain patients, and trials are underway in other cancers, including sarcoma and gastrointestinal cancers.
A surprising frontier: Autoimmune diseases
Perhaps one of the most surprising developments is the potential use of CAR T in autoimmune diseases such as lupus, systemic sclerosis and inflammatory muscle diseases. Early studies show that CAR T can “reset” the immune system, leading to long-lasting remission for some patients who had exhausted other options.
“This is garnering a lot of attention,” Dr. Maakaron said. “We may be able to help patients with devastating autoimmune diseases using the same therapies we first developed for cancer.”
Looking ahead
Immunotherapies like CAR T have changed the outlook for many patients with blood cancers, offering hope where survival once seemed unlikely. The field continues to advance, with new products aiming to be safer, faster and more widely available.
Dr. Maakaron emphasized that while challenges remain — including toxicity, access and cost — the progress is undeniable.
“CAR T and T-cell therapies really have wide applications for blood cancers and beyond,” he said. “They carry significant toxicities and require infrastructure, but the sooner we can start someone on this path, the better.”
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