Q3 2021: Additional information and data in acute leukemia

July 7, 2021

AML

A recent study shown that although the use of less-intensive therapies is associated with an increased risk of mortality in older patients with AML patients treated with these therapies also spend fewer days in the hospital. This study is the first step of reevaluating the role of intensity of therapy in AML and older patients that eventually could lead to improvement in the overall outcomes. It also highlights the importance of considering geriatric assessment for older patients with AML “to get a better sense of their overall health and not to rely on standard measures such as performance status scales or merely age”. (Ref: Sorror ML, Storer BE, Fathi AT, et al. Multi-site 11-year experience of less-intensive versus intensive therapies in acute myeloid leukemia. [published online ahead of print, 2021 Apr 28]. Blood. doi: 10.1182/blood.2020008812).

The use of combination chemotherapy, hypomethylating agents (HMAs) and/or hematopoietic stem cell transplantation (HSCT) are the current standard of treatment for AML. However, despite the many clinical benefits conferred by treatments for AML, health practitioners are facing challenges in managing associated toxicities that impact on the quality of life of patients. Treatment-related adverse events (TAEs) such as cardiotoxicity, hepatotoxicity, gastrointestinal toxicity, hematologic toxicity, immunological and pulmonary toxicity are common in patients with AML and contribute to treatment discontinuation and failure. Ravandi et al. provided updates on the phase III QUAZAR AML-001 trial, with a focus on onset of treatment-related gastrointestinal adverse events (AEs) in older patients with AML in first remission receiving oral azacitidine (AZA), along with the toxicity management criteria. Awareness about the possibility for GI events during early oral azacitidine treatment will facilitate patients and clinicians to pre-plan and introduce prophylaxis and symptomatic interventions, which in turn will increase treatment adherence and better outcomes. (Ref. Ravandi F, Pocock C, Selleslag D, et al. Gastrointestinal events and management strategies for patients with acute myeloid leukemia in first remission receiving oral azacitidine (CC-486) maintenance therapy in the randomized, placebo-controlled, phase III QUAZAR® AML-001 trial. Presentation #1036. ASH 2020; Dec 5−8, 2020; Virtual)

A phase III study has recently shown that Oblimersen (G3139) can be safely added to conventional chemotherapy for older patients with AML. The addition of G3139 to chemotherapy failed to improve outcomes of older AML patients, but patients with secondary AML had improved disease-free survival. (Ref. Alison R et al, https://doi.org/10.1182/bloodadvances.2021004233

MRD

In next-generation sequencing (NGS)-based MRD monitoring, the use of non-DNMT3ATET2, or ASXL1 (non-DTA) mutations may predict relapse and survival following allogeneic hematopoietic cell transplantation (alloHCT) for patients with AML, according to findings published. (Ref. Heuser M, Heida B, Büttner K, et al. Posttransplantation MRD monitoring in patients with AML by next-generation sequencing using DTA and non-DTA mutations. Blood Adv. 2021;5(9):2294-2304)

Patients with newly diagnosed AML treated with Ven+Aza who achieved CRc and an MRD response <10−3 had a longer DoR, EFS, and OS compared with those who did not achieve an MRD response (≥10−3). Higher rates of neutropenia were observed in patients that achieved an MRD response compared with those who did not. MRD response was also a significant predictor of OS, however, further studies are required to investigate the role of MRD response in clinical management. (Ref. Pratz KW, Jonas BA, Pullarkat V, et al. Measurable residual disease response in acute myeloid leukemia treated with venetoclax and azacitidine. Oral abstract #S137. European Hematology Association (EHA)2021 Virtual Congress; Jun 11, 2021; Virtual).

ALL

In this video, Chiaretti discusses the feasibility of improving the results of a chemotherapy-free regimen with dasatinib for patients with newly diagnosed Ph+ ALL.

APL

APL is a subtype of AML involving complex coagulopathy resulting in early mortality due to hemorrhagic events. Currently, all-trans retinoic acid (ATRA) with arsenic trioxide (ATO) is used as a frontline treatment in low-risk APL patients with excellent cure rates. The use of ATRA with ATO for high-risk APL patients is also under investigation. Despite the benefits offered by ATRA + ATO therapy, there are reports of varicella-zoster virus (VZV)the causative agent of herpes zoster (HZ)—reactivation in APL patients treated with ATO.

There is a variety of effective therapeutic agents in use to treat AML where each one of them has a distinctive mechanism of action and unique toxicity profile. However, awareness about the impact of adverse events of any treatment, and knowledge about the extent to which a patient can bear the treatment, allows to maintain a balance between prolonging survival and the quality of life of patients.

Strategies to stimulate normal production of CD4+ T cells and/or balance Tregs during the first 6 months of ATO therapy are needed to effectively control herpes zoster reactivation risk. (Ref. Glass JL, Derkach A, Hilden P. Arsenic trioxide therapy predisposes to herpes zoster reactivation despite minimally myelosuppressive therapy. Leuk Res. 2021;106:106569. DOI: 1016/j.leukres.2021.106569)

Acute leukemias and MDS

In patients with acute leukemias or myelodysplastic syndromes (MDS), those who underwent haploidentical relative hematopoietic cell transplantation (haploHCT) had higher rates of grade 3-4 graft-versus-host disease and mortality compared with those who underwent HCT with a matched unrelated donor (MUD), according to results recently published. These preliminary results would need to be investigated further. (Ref. Gooptu M, Romee R, St Martin A, et al. HLA Haploidentical versus matched unrelated donor transplants with post-transplant cyclophosphamide based prophylaxis. [published online ahead of print, 2021 Apr 13]. Blood. doi: 10.1182/blood.2021011281)

Open survey : Understanding patient’s burden, quality of life, and alignment of patient-reported outcome measures to capture changes in high-risk MDS/AML.

More information: https://www.mdsqualityoflifestudy.com/info-for-industry-experts-delphi-st

Link to participate to the survey: https://www.mdsqualityoflifestudy.com/delphi-contact-information

End of life

Patients with AML and their caregivers generally defer end-of-life (EOL) transfusion decisions to clinicians without participating in shared decision-making. This tendency may delay hospice admission in patients who would benefit from this care the most, according to a new study published. This research adds to a multitude of other studies suggesting hematologists struggle to navigate care decisions for patients and families at the EOL. We know patients with blood cancers are more likely than those with solid tumors to die in the hospital, spend time in an intensive care unit or emergency department near the EOL, or to receive chemotherapy in the last two weeks of life. Hematologic patients are also less likely to use hospice care services overall. (Ref. Cripe LD, Cottingham AH, Martin CE, Hoffmann ML, Sargent K, Baker LB. Bereaved informal caregivers rarely recall a relationship between transfusions and hospice in acute myeloid leukemia [published online ahead of print, 2021 Apr 29]. Am J Hosp Palliat Care. doi: 10.1177/10499091211013290)