Q4 2022: Additional information and data in acute leukemia

October 12, 2022

AML

This article by Larkin and colleagues describes a detailed analyses of survival differences between non-Hispanic Black adolescent and young adult (AYA) patients with AML vs non-Hispanic White patients. The authors compared non-Hispanic Black AYA patients with AML with non-Hispanic White patients treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology protocols. The authors compared early (<30 days) death rate, complete remission rate, and overall survival between the 2 groups, and they performed between-groups survival analyses across cytogenetic strata. They found that the outcome of Black AYA patients, especially those aged 18-29 years, was worse than the outcome of White patients receiving similar intensive therapy. The investigators concluded that reduced response rates to induction chemotherapy and leukemic clone persistence suggest a need for different treatment intensities and/or modalities in Black AYA patients with AML. They also call for a systematic change to patient care because of higher early death rates that are suggestive of a delay in diagnosis and treatment. Full article here.

The phase 3 QUAZAR AML-001 trial demonstrated that oral azacitidine (Oral-AZA) prolongs survival in patients with AML in remission after chemotherapy who are not candidates for stem cell transplantation. Döhner et al report on a subgroup analysis of Oral-AZA in patients with nucleophosmin 1 (NPM1) and FMS-related tyrosine kinase 3 (FLT3) mutations. Median survival is improved in all subgroups of patients with NPM1 or FLT3 mutations (alone or together) independent of other risk facts or measurable residual disease postinduction. Full article here or listen to podcast by clicking this link.

Wang et al present the results of a phase 3 study comparing gilteritinib plus azacitidine (GIL+AZA) to azacitidine alone (AZA) in newly diagnosed FLT3-mutated AML in patients ineligible for intensive induction therapy. GIL+AZA yielded higher remission rates, but neither event-free survival nor overall survival were significantly different, leading to the cessation of the trial for futility. Different approaches are required for unfit patients with FLT3-mutated AML. Full article here

Outcomes of older and unfit adults with AML differ significantly from their younger counterparts, owing to their adverse disease biology (complex karyotype, antecedent myelodysplastic syndrome) and age-related comorbidities.1 Recently, venetoclax-based lower intensity therapies were approved for newly diagnosed AML in older (aged ≥75 years) adults and/or those not eligible for intensive chemotherapy. Full article here

ALL

Bispecific antibodies retargeting T cells to malignant cells are emerging as highly effective options for several B-cell malignancies, but tumor heterogeneity and antigen loss reduce their effectiveness. Zhao et al tackle these problems by designing a trispecific antibody that can retarget T cells to cells expressing either CD19 or CD22 or both and demonstrates superior activity in vitro and in vivo over bispecific antibodies when the malignant cells express both antigens in preclinical models. The authors’ work holds potential promise as a new approach against B-cell acute lymphoblastic leukemia (B-ALL) when CD19 expression is heterogeneous. Full article here

Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive disease with suboptimal treatment options and a poor prognosis. Much of the literature derives from Japanese populations; however, ATLL is also seen in the Caribbean and amongst Caribbean immigrants to North America where recent reports highlight disparate prognostic and mutational profiles. This report by Zhao et al explores key transcriptional regulators between Japanese and North American ATLL cell lines and identifies ETS1 as a novel dominant oncogenic transcriptional regulator with overexpression in North American cell lines compared to Japanese cell lines. This distinction may identify novel treatment approaches for North American/Caribbean ATLL. Read full article here

CAR T-cell therapy

Through clinical correlative analyses, Ghobadi and colleagues describe a novel genomic modification outside of the transmembrane and antigenic domains of CD19 that drives resistance to CD19-targeted immunotherapies. This new mechanism of antigen escape adds to the growing understanding of resistance to CAR T-cell therapy. Article here.

Other

When the hematologist becomes the patient…

Here are three lessons I learned as a hematologist from being a patient:

  • Be comfortable sitting with uncertainty.
  • Offer silence as a gift to allow your patient to genuinely share deep fears.
  • Recognize the inevitable ambiguity and polarized emotions that arise around questions of mortality.

Although our expertise as hematologists is needed during active chemotherapy, our compassion as healers is just as essential to help patients navigate the transition after therapy, when the emotional impact often comes to the fore.

Full article here