Skip to Main Content

Advertisement intended for health care professionals

Skip Nav Destination

Solving Big Problems for Small Patients: Innovations in Pediatric Hematology Therapies

December 19, 2023
Hilary Whitworth, MD, MSCE (@HilaryWhitworth)
Children’s Hospital of Philadelphia, Philadelphia, PA

Given the relative rarity of hematologic disease in children compared to adults, pediatric clinical trials are often prohibitively expensive and time-consuming. As a result, many drugs are used off label based on recommendations from observational studies, expert opinion, or even case reports. Pediatricians made a strong appearance at this year’s annual meeting, with multiple abstracts highlighting newer therapeutics in children and adolescents within the full spectrum of hematology, proving, in the words of William Van Horne, that, “Nothing is too small to know. And nothing is too big to attempt.”  

Steven Pipe, MD, presented “Emicizumab Prophylaxis in Infants with Severe Hemophilia A Without Factor VIII Inhibitors: Results From the Primary Analysis of the HAVEN 7 Study.”  Historically, factor prophylaxis in infants with severe hemophilia was very challenging due to difficulties with intravenous access. In this study, about half of the evaluable infants had zero treated bleeds, and there were no intracranial hemorrhages. Nine participants had injection site reactions, but there were no emicizumab-related serious adverse events. It is thrilling to have data to support the use of emicizumab in infants, a practice many providers have already adopted.  

Extended half-life products are sticking around longer! “Once-Weekly Efanesoctocog Alfa Prophylaxis Provided High Sustained Factor VIII Activity Levels, Independent of Blood Group, in Children <12 Years of Age with Severe Hemophilia A” was presented by Flora Peyvandi, MD, PhD. In the study, participants who reached steady state — meaning factor VIII activity levels remained in the mild hemophilia range with once-weekly dosing — decreased the need for frequent IV accesses. 

In the same session, Lynn Malec, MD, presented data on qualitative interviews with 19 caregivers from this same trial in the abstract “Experiences with Efanesoctocog Alfa: Exit Interviews With Caregivers of Previously Treated Patients With Hemophilia A from the XTEND-Kids Phase 3 Clinical Trial.” The caregivers reported that their child’s mood, emotions, and physical activity were most impacted by hemophilia prior to enrollment, but that prophylaxis with efanesoctocog alpha had a positive effect on their child’s (and their own) daily life and functioning. These meaningful patient reported outcomes are extremely valuable as we consider the impact new therapies have on children and their families.   

On the malignant side, the Children’s Oncology Group (COG) provides a collaborative research framework for clinical trials that would otherwise be impossible at single institutions. Elliot Stieglitz, MD, presented “Efficacy of Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: A Report From the Children’s Oncology Group.”  He shared data on the use of trametinib in juvenile myelomonocytic leukemia (JMML), which was the first trial of a MEK inhibitor in a pediatric hematologic malignancy. JMML is a rare and aggressive disease in young children that ultimately requires hematopoietic stem cell transplantation. The authors reported on 10 participants who received trametinib with a 50% response rate, three of whom remained on trametinib off study, indicating there may be a subset of children who do not require stem cell transplant. This observation is currently being investigated in a subsequent trial.  

Post-marketing studies are also important for pediatric drugs, given the limitations in the trials that lead to Food and Drug Administration approval. Timothy T. Spear, MD, presented real-world data on calaspargase pegol-mknl (CalPEG) toxicity and serum asparaginase activity levels in his group’s abstract, “A Real-World, Single Institution, Post-Market Comparison of Pegaspargase and Calasparagase Pegol-Mknl Therapeutic Drug Monitoring and Toxicity.” Dr. Spear shared single-institution, retrospective data from 125 patients that demonstrated an increased incidence of pancreatitis in patients who received CalPEG and an increased incidence of venous thromboembolism in patients with T cell disease receiving CalPEG compared to pegaspargase (PEGasp). Despite an increased incidence of allergy in PEGasp versus CalPEG cohorts, the rates of total asparaginase-related toxicity between the two products were similar. Importantly, these findings are different from the published trials for CalPEG. As Dr. Spear shared, “Clinical trials are valuable tools, but they don't always reflect real-world scenarios with varied demographics, different institutions, different institutional standards.” He cautioned that their data “still need to be evaluated in larger cohorts to make sure [our] findings are translatable to our broader population, just as findings in clinical trials still need to be upheld in the larger community.” 

It is clear from the science presented that there is no challenge too large for pediatricians. Our patients may be small, but our dedication, perseverance, and advocacy are big, and we will work tirelessly to level the playing field. This is the best time to be involved in the care of kids!                                  

 

Dr. Whitworth indicated no relevant conflicts of interest. 

Close Modal

or Create an Account

Close Modal
Close Modal