Managing AML in Younger Patients With Promising Therapies, Supportive Care Drugs

New therapies for managing acute myelogenous leukemia (AML) are showing promise in recent studies. Data for these drugs—indicated to treat children, adolescents and young adults with AML—and discussion about supportive care strategies were presented during the first Advanced Topics for Oncology Pharmacy Professionals (ATOPP) conference.¹

Outcomes for patients younger than 18 years of age with AML have improved over the past 30 years and these patients currently have an overall survival rate of 70%. According to researchers, although chemotherapy, risk classification, supportive care, and minimal residual disease monitoring have all intensified or improved, novel therapeutic approaches are needed to further increase AML survival in younger patients.²

In the ATOPP session, presenter Jennifer Young, PharmD, BCOP, clinical pharmacy specialist for pediatric hematology/oncology at Cincinnati Children’s Hospital Medical Center in Ohio, discussed CPX-351 (Vyxeos; Jazz Pharmaceuticals), a lipsome-encapsulated novel formulation of 2 chemotherapies: daunorubicin and cytarabine. The combination drug blocks the growth of cancer cells and is currently approved by the FDA for the treatment of adult patients with certain types of AML.¹

“This liposomal formulation has 2 major benefits: kinetic advantages provided by the liposomes, and the ability to deliver these drugs in a defined 1:5 molar ratio [daunorubicin to cytarabine] to the target cells,” Young said.

According to Young, studies have found benefits to CPX-351 that include prolonged time in circulation, altered bio-distribution that leads to decreased toxicity to normal tissue, and circumvention of drug efflux transporters that are responsible for drug resistance. Overall, she said, the goal for using CPX-351 is to minimize cardiotoxicity while also maintaining efficacy.¹

In the presentation, Young highlighted the findings of the AAML 1421 (NCT02642965) trial, which found more superior response rates than other North American studies in children with AML in first relapse. This trial also found that toxicity was manageable and protocol therapy was effective. Investigators are recommending a dose of 135 units/m2 IV on days 1, 3, and 5 of the cycle for younger patients.³

The ATOPP session also touched upon FLT3 targeted therapies, such as sorafenib (Nexavar; Bayer), midostaurin (Rydapt; Novartis), and gilteritnib (Xospata; Astellas). According to Young, studies show that treatment with an FLT3 targeted agent is appropriate for all patients who are FLT3/ITD-positive without favorable cytogenetic and molecular features because of poor outcomes from use of conventional chemotherapy. There are currently data available to support sorafenib and midostaurin in pediatric patients with AML, and a phase 3 study for gilteritnib is enrolling individuals.¹

Additionally, Young presented data on gemtuzumab ozogamicin (Mylotarg; Pfizer), a humanized CD-33 directed monoclonal antibody-drug conjugate.1 The drug is indicated for patients aged 1 month and older with newly diagnosed CD33-positive AML, and for patients 2 years of age and older with relapsed or refractory CD33-positive AML.⁴

This drug is currently standard practice in upfront AML therapy and has shown improved survival rate in patients with favorable cytogenetics. According to Young, data from studies with adult patients taking gemtuzumab ozogamicin generally show no benefit to those with high-risk cytogenetics.¹

In subgroup analyses to identify the benefit of gemtuzumab ozogamicin, CD33 expression was measured in patients with AML across 4 quartiles. The first quartile, which had low CD33 expression, showed no survival benefit with the drug; however, patients in the second-fourth quartiles with higher CD33 expressions showed 5-year event-free survival with gemtuzumab ozogamicin (53% vs 41%, p=0.005) and 5-year decreased relative risk (32% vs 49%, p<0.001).⁵

“This stands to reason, that patients with a higher expression of gemtuzumab [ozogamicin]’s target will have higher benefit with the use of gemtuzumab ozogamicin,” Young said.

The session also addressed supportive care therapies. According to Young, current approaches for decreasing cardiotoxicity in patients with AML include use of liposomal anthracycline formulations, dexrazoxane cardioprotection, and decreasing anthracycline expsosure.¹

Additionally, levofloxacin should be considered as an antibacterial prophylaxis in certain children with AML for the reduction of risk of bacterial infections and mortality.¹

REFERENCES

1. Young J. Bringing things into focus: recent updates in the management of acute myelogenous leukemia (AML) in younger patients. Presented at: ATOPP Summit; June 24-26, 2021.
2. Lonetti A, PessionA, Masetti R. Targeted therapies for pediatric AML: Gaps and perspective. Front Pediatr. 2019; 7: 463.
3. Cooper TM, Absalon MJ, Alonzo TA, et al. Phase I/II Study of CPX-351 Followed by Fludarabine, Cytarabine, and Granulocyte-Colony Stimulating Factor for Children with Relapsed Acute Myeloid Leukemia: A Report from the Children’s Oncology Group. J Clin Oncol. 2020; 38(19): 2170-2177.
4. Mylotarg prescribing information. Pfizer. 2021. Accessed June 24, 2021. https://www.pfizerpro.com/product/mylotarg/newly-diagnosed-pediatric-aml-combination-regimen?advert=advert
5. Pollard JA, Loken M, Gerbing RB, et al. CD33 Expression and its association with gemtuzumab ozogamicin response: results from the randomized phase III COG trial AAML0531. J Clin Oncol. 2016; 34: 747-755.