Q1 2023: Additional information and data in acute leukemia

January 20, 2023

AML 

Intensive chemotherapy before alloHCT doesn not improve survivail in AML: data from the phase III ASAP trial presented at the 64th ASH Annual Meeting and Exposition showed no benefit to undergoing intensive remission induction chemotherapy before alloHCT compared to watchful waiting and sequential conditioning before alloHCT. (Ref: Schetelig J, Stelljes M, Middeke JM, et al. In patients with relapsed/refractory AML sequential conditioning and immediate allogeneic stem cell transplantation (allo-HCT) results in similar overall and leukemia-free survival compared to intensive remission induction chemotherapy followed by allo-HCT: results from the randomized phase III ASAP trial. Abstract #4. Presented at the 2022 American Society of Hematology Annual Meeting and Exposition; December 11, 2022; New Orleans, Louisiana.)

Co-mutation patterns allowed for updated risk stratification of NPM1-mutated AML: many patients with NPM1-mutated AML carry at least three gene mutations, and consideration of these co-mutational patterns is necessary for accurate risk stratification, according to data presented at the 64th ASH Annual Meeting and Exposition. (Ref: Hernández Sánchez A, Ramiro AV, Strang E, et al. Machine learning allows the identification of new co-mutational patterns with prognostic implications in NPM1 mutated AML – results of the European Harmony Alliance. Abstract #304. Presented at the 2022 American Society of Hematology Annual Meeting and Exposition; December 10, 2022; New Orleans, Louisiana).

Enasidenob vs conventional care in older patient with late-stage mutant-IDH2 relapsed/refractory AML: the  open-label, randomized, phase 3 trial (NCT02577406) compared enasidenib, an oral IDH2 inhibitor with conventional care regimens in patients aged ≥60 years with late-stage, mutant-IDH2 AML R/R to 2 or 3 prior AML-directed therapies did not meet its primary study endpoint was not met, but OS was confounded by early dropout and subsequent AML-directed therapies. Enasidenib provided meaningful benefits in EFS, TTF, ORR, HI, and RBC-TI in this heavily pretreated older mutant-IDH2 R/R AML population. (Ref: https://doi.org/10.1182/blood.2021014901)

A prospective, observational study enrolled patients presenting for treatment of AML at 13 institutions to analyze associations between hematopoietic cell transplantation (HCT) and survival, quality of life, and function in: the entire cohort, those aged ≥65 years, those with high comorbidity burden, intermediate cytogenetic risk, adverse cytogenetic risk, and first complete remission with or without measurable residual disease.

Key points:

  • Models adjusted for AML and patient-specific variables showed no benefit of allogeneic HCT in patients that are older or medically infirm.

  • Current practice of offering HCT to older and medically infirm patients with AML is not evidence based, which calls for randomized trials.

Ref: https://doi.org/10.1182/blood.2022016916

ALL

Use of the anti-CD19 bispecific T-cell engaging antibody blinatumomab given in conjunction with the tyrosine kinase inhibitor (TKI) dasatinib may provide an alternative to allogenic transplant for older adults with Ph+ALL. What was unique about the trial is that it strictly included patients older than 65 years, allowed comorbidities, and only one patient proceeded to allogenic transplant. Moreover, previous research used ponatinib in conjunction with blinatumomab, but ponatinib may not be a good option for older patients given its risk for cardiovascular events. (Ref. Advani AS, Moseley A, O’Dwyer KM, et al. Dasatinib/prednisone induction followed by blinatumomab/dasatinib in Ph+ acute lymphoblastic leukemia [published online, 2022 Nov 2]. Blood Adv. doi: 10.1182/bloodadvances.2022008216.

Fertility 

An advanced practitioner-driven fertility preservation initiative introduced at a community oncology practice resulted in a more than two-fold increase in referrals for fertility preservation consultation with a reproductive endocrinologist among adolescents and young adults (AYAs, age 15-39) at risk for infertility. (Valdez C. Early identification for fertility preservation improves referrals in a community oncology practice. Presented at JADPRO Live 2022, Aurora, Colorado).