Advances in acute leukemia: new therapies and clinical trials

The treatment of acute leukemia has seen dramatic shifts over the past decade. Innovations in targeted therapy and immunotherapy, as well as a new understanding of dosing and sequencing strategies, have rapidly expanded treatment options for both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Those developments are making early diagnostic and treatment decisions more consequential than ever.

“There’s been an explosion of new leukemia drugs in recent years,” says Catherine E. Lai, MD, MPH, an Associate Professor and Physician Leader of the Leukemia Clinical Research Unit at the University of Pennsylvania’s Perelman Center for Advanced Medicine. “While this counts as a huge success, it also means treatment decisions have gotten much more complicated,” she adds.

That complexity has implications for how and where patients are evaluated and treated. Referral to a specialty leukemia center early in the disease course can ensure that patients benefit from advanced diagnostics, disease-specific expertise, and access to clinical trials that may meaningfully alter prognosis.

Leukemia diagnosis and treatment evolve

In the United States, approximately 22,000 new cases of AML and 6,000 new cases of ALL are diagnosed each year, according to the American Cancer Society. At Penn Medicine, those diagnoses typically begin with a bone marrow biopsy and full diagnostic workup. Patients are then risk-stratified based on their functional status and findings from molecular testing. This approach balances the aggressiveness of the disease with the patient’s ability to tolerate intensive therapy.

Recent research has underscored the value of that molecular analysis. “In the past, it was thought that we needed to start treatment urgently for acute leukemias,” Dr. Lai explains. “But now we have evidence that for patients who are clinically stable, it’s safe to wait until all the molecular testing comes back before deciding on a treatment course.”

Those findings inform the intensity of initial therapy as well as eligibility for targeted agents, immunotherapies, and transplant strategies. Waiting for those results does not negatively affect response rate or survival rate, says Dr. Lai, and allows hematologist-oncologists to more accurately tailor the treatment to increase the odds of a good response.

Traditionally, treatment starts with intensive chemotherapy, which, until recently, involved drugs that have been in use for decades. In the last 10 years, however, more than a dozen new agents have been approved for leukemia. This flurry of new options places a premium on clinical experience.

“These are relatively rare diagnoses, but at a high-volume center like Penn Medicine, we have experts who treat leukemia patients day in and day out,” observes Dr. Lai. “That gives us a great depth of knowledge about the many treatment options now available, including investigational treatments.”

In addition to leukemia specialists, Penn Medicine also has physicians who specialize in bone marrow transplant, an important and potentially curative treatment option for many patients with AML and some with ALL. The Penn Medicine Cell Therapy and Transplant Program is one of the largest in the country, having completed more than 2,200 allogeneic transplants and more than 5,500 autologous transplants to date.

New treatments and clinical trials for acute leukemias

Penn Medicine is actively involved in both investigator-initiated clinical trials and large industry-sponsored trials. “With new treatments and new data about leukemia coming out all the time, it’s an exciting time for our field,” says Dr. Lai. Many of these emerging therapies are advancing along parallel tracks, reshaping treatment paradigms in ALL and AML while also moving rapidly through clinical trials.

Advances in AML treatment

Several new targeted therapies have been developed to target AML. One such agent is the BCL2 inhibitor venetoclax, which can interfere with cancer cells’ survival and make the cells more vulnerable to chemotherapy. “Venetoclax has revolutionized treatment for patients who cannot tolerate intensive chemotherapy,” says Dr. Lai, who notes that because the drug can cause significant cytopenia, there are important nuances in how venetoclax is dosed and scheduled to manage side effects.

In addition to venetoclax, new targeted therapies such as FLT3 inhibitors, IDH inhibitors, and menin inhibitors have been a welcome addition to the treatment arsenal but require further refinements to treatment models. “Now the field is looking at how best to combine and sequence those drugs to continue to improve outcomes,” Dr. Lai says.

Advances in ALL treatment

While innovation in AML has largely centered on targeted therapies and optimized combinations, advances in ALL have been driven by immunotherapy. In ALL, several new immunotherapy treatments have made an impact on overall survival and leukemia-free survival, Dr. Lai says. One such advance is blinatumomab, a bispecific T cell engager that helps the immune system target cancer cells. Other important developments include approval of the CAR T cell therapy agents tisagenlecleucel, brexucabtagene autoleucel, and obecabtagene autoleucel for the treatment of B-cell ALL.

Leukemia clinical trials

Treatment for AML and ALL is continuing to evolve, and Penn Medicine is engaged in a variety of leukemia clinical trials to test emerging therapies. This research includes investigator-initiated trials spearheaded by Penn Medicine physician-scientists, as well as a wide variety of large multisite trials and cooperative group trials.

Among those opportunities, Penn Medicine offer patients access to several national programs:

• The Blood and Marrow Clinical Trials Network, a NIH-funded program designed to improve outcomes of blood and marrow transplantation
• The ECOG-ACRIN Cancer Research Group, a scientific organization that designs and conducts cancer research involving adults who have or are at risk of developing cancer
• Myeloid Malignancies Molecular Analysis for Therapy Choice (MyeloMATCH), a precision medicine clinical trial program that uses rapid genetic sequencing to match myelodysplastic syndrome and AML patients to trials of suitable targeted therapies

Referring patients to Penn Medicine

Referral to Penn Medicine provides patients with access to the latest treatments, including promising investigational therapies. Referring as soon after diagnosis as possible can expand patients’ treatment options by connecting them with trial opportunities before they begin down a treatment path. “Once patients start treatment, they may become ineligible for a lot of clinical trials,” Dr. Lai adds. “Early referrals are a valuable way to connect patients to study opportunities and to the most current commercial therapies.”

Whenever possible, Penn Medicine’s blood cancer team collaborates with referring physicians so that patients can receive care in their communities.

Referrals and consultations

To refer a patient to the Penn Medicine Division of Hematology and Oncology, call 877-937-7366 or refer a patient online.