Q2 2021 : Additional information and data in acute leukemia

April 14, 2021

Here is a retrospective on additional data and information published in the second quarter of 2021.

AML

Patients over 65 who are newly diagnosed with AML currently have a poor prognosis, due to the toxicity and limited efficacy associated with high-intensity chemotherapy. A recent study has shown data demonstrating potential use of azacitidine as a backbone in induction and consolidation therapy combinations for elderly patients with AML, as opposed to LDAC. (Source: https://aml-hub.com/medical-information/flugaza-trial-azacitidine-vs-semi-intensive-chemotherapy-for-older-patients-with-newly-diagnosed-aml)

Initial findings from a proof-of-concept study suggest that UniCAR, a universal, rapidly switchable second-generation chimeric antigen receptor (CAR) T-cell therapy platform, could offer a new treatment option for patients with relapsed/refractory AML.

Secondary AML

The FDA has approved a revised label for liposomal daunorubicin and cytarabine, CPX 351, to include a new indication for the treatment of newly diagnosed secondary AML or AML with myelodysplasia-related changes in children aged one year and older. (Source; Source: Jazz Pharmaceuticals press release, March 30, 2021)

For patients with MDS or low-blast secondary AML, allogeneic hematopoietic cell transplantation (AHCT) is the only potentially curative treatment option. However, debate persists around the balance of benefits and risks associated with disease reduction using hypomethylating agents or induction chemotherapy prior to transplantation. Experts agree to say  that we need proper randomized studies using an active agent. The UniCAR platform uses targeting molecule TM123 and a single-chain variable fragment that is directed against the CD123 antigen. Since the time of the study’s publication, all patients have demonstrated a clinical response to treatment. A partial remission was observed in one patient, while two patients had complete remission with incomplete hematologic recovery (CRi). In one patient with CRi, the disease was still under control approximately 100 days after administration of treatment, while the other patient with CRi experienced regrowth after one month. (Ref: Wermke M, Kraus S, Ehninger A, et al. Proof-of-concept for Rapidly Switchable Universal CAR-T Platform with UniCAR-T-CD123 in relapsed/refractory AML. Blood. 2021 Feb 23. [Epub ahead of print])

Compared with conventional cytogenetic analysis (CCA), next generation sequencing (NGS)–based karyotyping offered greater insight into the prognosis of patients with intensively treated AML particularly through its ability to better detect copy number alterations (CNAs). Preliminary findings suggest that NGS-based approaches, given their increased precision and sensitivity, could replace CCA for karyotyping. but also emphasize the need for future research to investigate and develop new NGS-based prognostic markers. This may also improve individualized AML treatment. (Ref. Mareschal S, Palau A, Lindberg J, et al. Challenging conventional karyotyping by next-generation karyotyping in 281 intensively treated patients with AML. Blood Adv. 2021;5:1003-1016. doi:10.1182/bloodadvances.2020002517)

Pediatric AML

Treatment refusal and death as a result of toxicity account for most treatment failures among children with AML in resource-constrained settings. A recent study reported the results of treating children with AML with a combination of low-dose cytarabine and mitoxantrone or omacetaxine mepesuccinate with concurrent granulocyte colony-stimulating factor (G-CSF) (low-dose chemotherapy [LDC]) for remission induction followed by standard postremission strategies and provided long-term follow-up:

-Most children with de novo AML experience complete hematologic remission when treated with minimally myelosuppressive therapy plus G-CSF.

-Reduced-intensity induction decreases toxicity without adversely affecting the long-term outcomes in children with newly diagnosed AML.

(Ref. https://ashpublications.org/bloodadvances/article/5/7/1837/475622/
Minimally-myelosuppressive-regimen-for-remission?utm_source=&utm_medium=email&utm_campaign=adv_not_5_7)

ALL

Being overweight or obese during B-cell ALL induction is associated with chemoresistance as quantified by minimal residual disease (MRD). A study shown that integrating caloric restriction into B-ALL induction is feasible, reduces fat gain in the overweight, and improves disease response. The IDEAL trial is the first prospective trial to test caloric and nutrient restriction plus exercise as a therapeutic modality to improve chemotherapy efficacy and disease response in a hematologic malignancy. (Ref. https://ashpublications.org/bloodadvances/article/5/7/1853/475625/Caloric-and-nutrient-restriction-to-augment?utm_source=&utm_medium=email&utm_campaign=highlights_4_20_21&utm_source=sfmc&utm_medium=email&utm_campaign=BA+Highlights_4_20_21&utm_term=Link+Text+%c2%bb&utm_id=91282&sfmc_id=19426595)