Immunotherapy Superior to Chemotherapy for Children with Relapsed B-ALL

(Orlando, Dec. 10, 2019) — The immunotherapy drug blinatumomab significantly improved survival in children with relapsed B-acute lymphoblastic leukemia (B-ALL) compared with standard chemotherapy in a study presented today during the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando. Researchers say the results support blinatumomab as a new standard of care for high- and intermediate-risk relapsed B-ALL patients who are preparing to receive a bone marrow transplant. 

“From past experience, our understanding is that bone marrow transplant is the therapy that gives these children and young adults the best chance of a cure,” said lead study author Patrick A. Brown, MD, of the Johns Hopkins Kimmel Cancer Center. “Based on our study, it appears that blinatumomab is a much more effective bridge to transplant for this patient population, leading to a much larger portion of patients who are actually able to receive a bone marrow transplant. We believe that is the reason for the striking improvement in survival among patients who received blinatumomab.”

Blinatumomab is a bispecific T cell engager (BiTE^®) antibody construct that binds specifically to CD19, a protein expressed on the surface of B cells, and CD3, a protein expressed on the surface of T cells. Blinatumomab is currently approved by the FDA for use in relapsed and refractory B-ALL patients, but this is the first trial to confirm its benefits in pediatric patients who have minimal residual disease (MRD) following an initial course of chemotherapy after relapse. Patients in this group are frequently unable to proceed to a bone marrow transplant and face a high rate of subsequent relapse and death. 

The standard course of treatment for these patients is three months of chemotherapy leading up to a bone marrow transplant if possible. In the study, all patients first received one month of standard chemotherapy treatment. Researchers then identified 208 patients who were considered to have high- or intermediate-risk disease based on the timing of their relapse or the presence of MRD, and randomized these patients into two groups. One group received two months of blinatumomab therapy while the control group received the standard course of two additional months of chemotherapy. 

The researchers tracked disease-free survival, which was the trial’s primary endpoint, along with overall survival, ability to proceed to transplant, changes in MRD, and adverse events. Trial enrollment was stopped early after an interim analysis found the benefits of blinatumomab were substantial enough to establish it as a new standard of care.

After a median follow-up of 1.4 years, patients receiving blinatumomab showed a significantly higher rate of disease-free survival (59% compared to 41% in the control group), overall survival (79% compared to 59% in the control group), and ability to proceed to transplant (73% compared to 45% in the control group). Among patients with detectable MRD after the first month of chemotherapy, 79% of those receiving blinatumomab achieved undetectable MRD compared to just 21% among those receiving chemotherapy alone. 

Blinatumomab works by helping the body’s own immune cells find and destroy cancer cells. Like previous studies, the trial showed blinatumomab had significantly fewer side effects than standard chemotherapy, which works by killing all cells that are growing, including non-cancerous ones. Patients in the control group suffered significantly more fevers, infections, sepsis, and inflammation of the digestive tract lining known as mucositis; four patients in this group died from the toxic effects of chemotherapy. Some patients receiving blinatumomab experienced some adverse events known to be associated with blinatumomab including cytokine release syndrome, seizures, and other forms of nerve damage, all of which fully resolved. No patients who received blinatumomab died. 

The researchers will continue to track enrolled patients to assess longer-term outcomes. Dr. Brown noted that the study findings establish blinatumomab as a new standard of care only for patients with the risk profiles examined in the study, not for lower-risk patients or those who have not experienced relapse. Further research is needed to examine the potential benefits of using immunotherapy earlier in the B-ALL treatment cycle and to find out whether blinatumomab therapy can be further optimized through combinations with other therapeutic approaches, Dr. Brown said.

The trial (AALL1331) was led by the Children’s Oncology Group (COG), part of the National Cancer Institute (NCI)-sponsored National Clinical Trials Network. NCI is part of the National Institutes of Health. Amgen provided blinatumomab for the study under a Collaborative Research and Development Agreement with NCI.

The study authors and press program moderator will be available for interviews after the press conference or by telephone. Additional press briefings will take place throughout the meeting on VTE, sickle cell disease, inclusive medicine, and CAR-T and beyond. For the complete annual meeting program and abstracts, visit www.hematology.org/annual-meeting. Follow @ASH_hematology and #ASH19 on Twitter and like ASH on Facebook for the most up-to-date information about the 2019 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH publishes Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, which is available weekly in print and online. In 2016, ASH launched Blood Advances (www.bloodadvances.org), an online, peer-reviewed open-access journal.

CONTACTS:

Adam Silverstein, FleishmanHillard 
917-697-9313; [email protected] 

Leah Enser, ASH 
202-552-4927; [email protected]