Q4 2023: Additional information and data in acute leukemia

December 6, 2023
APL

Impact of the ICAL on the treatment of acute leukemia; The International Consortium on APL (IC-APL) is an initiative of the International Members Committee of the American Society of Hematology, created in the spirit of international clinical and laboratory collaboration with the aim of reducing the difference in the outcomes of patients with APL treated in developed and developing countries. It congregates leaders of well-established cooperative groups in Europe and North America, and hematologists in Brazil, Chile, Peru, Uruguay, and Paraguay. APL was initially selected as a model disease to test the impact of networking on outcomes because it is a highly curable disease if early diagnosis and specific treatment are promptly established. Full article: https://doi.org/10.1182/bloodadvances.2017002147

ALL

Short_NGS vs BCR-Abl PCR_AmJHematol 2023

The takeaways from the data are:

  • clonoSEQ is more prognostic in Ph+ ALL than traditional BCR-Abl RT-PCR
  • The differing prognostic values of these two assays for these patients are consistent with other reports that the lymphoid component (as measured by clonoSEQ) is distinct from, and more aggressive than, the myeloid component (as measured by BCR-Abl RT-PCT).
AML

Midostaurin plus daunorubicin or idarubicin for young and older adults with FLT3-mutated AML: RATIFY phase 3b trial:

In this study, midostaurin in combination with intensive chemotherapy provided high response rates, irrespective of patient age, induction regimen (“7+3” or “5+2”), or the type of anthracycline used (daunorubicin or idarubicin) during the induction therapy. Overall, 80.7% of patients achieved CR + CRi and 65.3% of patients achieved CR, with similar rates observed in patient subgroup analyses based on age, induction regimen, induction drug, and gender. These response rates support the results observed in the RATIFY study, in which 59% of patients who received midostaurin achieved CR.21 The results from this study also align with those from a phase 2 study (the German-Austrian AMLSG trial) of midostaurin in combination with standard induction and consolidation chemotherapy, followed by SCT, which allowed for enrollment of adult patients aged up to 70 years; similar CR + CRi rates were observed after induction in younger and older patients, with a manageable safety profile.24,25 Furthermore, the multivariate analysis from the AMLSG trial showed significant beneficial effect of midostaurin on EFS and OS in both younger and older patients (61-70 years). Full article: https://doi.org/10.1182/bloodadvances.2023009847

Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory AML: 

 Identification of a recommended phase 2 vibecotamab dose comprised 3 step-up doses (Week 1), which were noted to reduce cytokine response syndrome (CRS), followed by weekly dosing (1.7 μg/kg, Cohort -1D). In 16 of 120 patients, at least 1 treatment-emergent adverse event was classified as a dose-limiting toxicity. CRS, the most common adverse event (59.2%), managed with premedication, were mostly ≤grade 2. A secondary objective was assessment of efficacy in patients with CD123-expressing leukemias. A total of 10 of 111 (9.0%) efficacy-evaluable patients with AML achieved an overall response of morphologic leukemia-free state or better with an overall objective response rate (ORR) of 9.0%. Response was only observed in patients receiving a target dose of 0.75 μg/kg or higher (n = 87) in which the efficacy-evaluable ORR was 11.5%. Response was associated with lower baseline blast counts in blood and bone marrow (<25%) suggesting potential benefit. (Ref: https://doi.org/10.1182/bloodadvances.2023010956)

Cigarette smoke exposure accelerates AML progression in FLT3-ITD models

Past work reports smokers with AML have worse survival outcomes than nonsmokers; however, to the best of our knowledge, this is the first study to model cigarette smoke exposure in FLT3-mutant AML–bearing mice to examine potential molecular mediators of leukemia progression and chemotherapy resistance. SE accelerated disease progression in 3 FLT3-ITD AML mouse models. SC upon leukemia engraftment slowed acceleration, providing the first evidence that smoking and cessation deliver “go” and “no-go” signals to FLT3-ITD AML cells. Because many patients with cancer continue smoking after their diagnosis, these data from xenograft models provide evidence for cessation recommendations, but it will require further validation in primary AML samples. Additionally, mass cytometry revealed that SE increased protein expression of MCL-1, DNMT3B, and RUNX1. MCL-1 inhibitors are currently being investigated for AML treatment, especially in association with resistance to venetoclax,and RUNX1 mutations occur in 10% of patients with AML and are associated with inferior prognosis. Cumulatively, our data provide novel insights into previously undescribed molecular regulators of aggressive disease seen in patients with AML with histories of smoking. (Ref: https://doi.org/10.1182/bloodadvances.2023010111)

Vitamin C and D supplementation in AML

  • Vitamin C/D treatment was associated with less complications during chemotherapy and restores the vitamin D level before allogeneic hematopoietic cell transplantation in patients with AML.

  • Vitamin C/D treatment was not associated with better OS except in patients with AML with NPM1 mutations.

Full article: https://doi.org/10.1182/bloodadvances.2023010559

Transplantation

A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an alternative treatment to patients with high-risk acute leukemia lacking a human leukocyte antigen-matched donor. An analysis comprising 173 adults with AML and 93 with ALL who received a haplo-HSCT in Europe. All grafts were T cell–depleted peripheral blood progenitor cells from a direct family or other related donor. The results show that haplo-HSCT can be an alternative option for the treatment of high-risk acute leukemia patients in remission, lacking a human leukocyte antigen-matched donor. (ref: https://doi.org/10.1182/blood-2008-02-140095)

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