Q4 2023: Additional information and data in acute leukemia

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)

More

Recent articles in leukemia: leukemia | Page 1 | Search Results | American Society of Hematology (ashpublications.org)

ALAN’s abstract submitted and accepted for ASH

Earlier this year, ALAN submitted an abstract Understanding Relapsed/Refractory Acute Leukemia Patients Treatment Preferences: Insights from Qualitative Research, ” for the 65th annual meeting and exposition of American Society of Hematology (ASH) to be held from December, 9th to 12th 2023.

The abstract has been selected by ASH Program Committee for a poster presentation during the congress.

Here are our presentation details:

Session Name: 903. Health Services and Quality Improvement –Myeloid Malignancies: Poster II
Session Date: Sunday, December 10, 2023
Presentation Time: 6:00 PM – 8:00 PM
Location: San Diego Convention Center, Halls G-H

Publication Number: 3730
Title:
Understanding Relapsed/Refractory Acute Leukemia Patients Treatment Preferences: Insights from Qualitative Research

Link to the abstract: https://doi.org/10.1182/blood-2023-172871

We have another abstract which was submitted

Title: A Study to Demonstrate Impact of Active Referral of Acute Leukemia Patients and Families to Patient Organization at Diagnosis

Link to the abstract: https://doi.org/10.1182/blood-2023-173421

Spotlight on ALAN members

In 2023, with ALAN support, some of our members have been able to start and/or complete projects which benefit acute leukemia patients and their families. We are very grateful that our support could contribute to make these projects happen.

Aim: Provide an educational kit on bone marrow transplantation (BMT) to patients over 18 years of age, diagnosed with acute leukemia.

Number of kits: 1,000 units

1.Educational booklet on BMT prepared from the vision and needs of the patient. It includes an analogy with a garden of plants to better explain the procedure.

2.Animated educational video (3 – 4 min) that explains BMT clearly and simply through analogy. The video can be accessed through a QR code inserted in the primer.

3.Diary to capture emotions, feelings, achievements, dreams and the most important events during the hospitalization process. View it here: Diary

4.Schedule of activities so that patients can plan their activities during hospitalization. Isolation is often hard to bear, but planning simple, motivating activities will help you get through this time.

5.Hobby book with word searches, crossword puzzles, riddles and more fun games related to acute leukemia and other topics of interest

6.Explanatory video capsules by a BMT specialist, who answers frequently asked questions from patients such as those related to the apheresis process, or graft versus host disease.

7.Video capsules of transplant patients where they share recommendations, experiences and messages of trust

Project summary: Project BMT toolkit

Aim: Donation of materials to San Juan de Dios hospitals and World Leukemia Day 

Activities:

1.Educational talks on Leukemia, chronic, acute, advanced phases, transplant, nutrition and cancer, importance of PCR, adherence etc

2.Raffle

3.Donations in medicines, disposable medical supplies (nitrile gloves, syringes, disposable gowns for medical personnel, blood transfusion bags , laboratory and blood bank materials), wheelchairs, digital scales, digital thermometers, hospital desinfection kit, cloth gowns for examination, gifts for patients and doctors.

Aim: Cancer control through awareness, patient support and advocacy – a multifaceted approach

1.Rebuild the community by inviting the patients in the ward to join, so that they can maintain contact and close peer support even after leaving the hospital

2.Engage a psychologist to talk to the patients individually

3.Continuous medical education for health workers on Leukemia – HENZO Kenya is working closely with the Kenya Network of Cancer Organization (KENCO) in offering webinars on leukemia.

4.Printing and distribution of AML/ALL materials: Over 10,000 booklets developed and distributed to a number of cancer treatment centers across the country

5.Commemoration of annual leukemia days/months – HENZO Kenya has taken advantage of the hype created by national/international cancer commemoration days/months to accelerate creation of awareness on leukemia especially through mainstream media slots.

6.Advocacy to ensure availability of cancer services: Universal Health Coverage is being rolled out nationally. UHC favours early detection and treatment. The Government plans to restructure the National Hospital Insurance Fund to provide cover for screening and diagnostics, currently not being offered.

7.Support to acute leukemia patients: A number of acute leukemia patients have been assisted with accommodation costs support, and NHIF premiums payment support, psycho-social counseling to support patients individually who are admitted in the National Hospital (KNH), set up of a support group.

Project summary: Project cancer control

Aim: Raise awareness and expand the access to information about acute leukemia

Summer Information Booths: During the summer, information booths were organized at various locations to raise awareness about leukemia. These booths served as platforms to educate the public about the disease, its symptoms, and available treatment options. Additionally, we provided opportunities for blood donation and bone marrow registration

Unfortunately, the project has faced some challenges in recent months. A scandal involving theft and illegal sale of cancer treatment/therapy has emerged, leading to the director’s decision to ban hematologists from speaking at events, educational videos, and TV appearances. This unexpected development has disrupted all planned activities and forced us to postpone certain project initiatives.

Activities are rescheduled for late winter and these activities will include educational seminars, awareness campaigns, and TV appearances events. We believe that by resuming our efforts, we can effectively raise awareness about leukemia and provide support to those in need.

Project summary: Project: leukemia awareness

Aim: translation in arabic of materials

Aim: leukemia material in czech

Q3 2023: Additional information and data in acute leukemia

AML

Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML: 

Olutasidenib is a new, selective small molecule inhibitor of IDH1 recently approved by the FDA; thus, it has become the second approved IDH1-targeted agent for the treatment of relapsed/refractory IDH1 mutant acute myeloid leukemia (AML). Overall response rate was 48% with complete remission/incomplete blood count recovery of 35%, and, importantly, response rates were similar in patients who had and who had not received prior venetoclax. (Ref: https://doi.org/10.1182/bloodadvances.2022009411)

FLT3-ITD does not predict inferior prognosis in AML patients aged ≥60 years

FLT3 internal tandem duplications (ITD) mutations are found in 25% of patients with AML. In younger patients, FLT3-ITD is associated with increased relapse and decreased survival. However, there are limited data on the prognostic implication of FLT3-ITD+ in older patients (aged ≥60 years) who received treatment, particularly, after the approval of FLT3 inhibitors and venetoclax.

Findings from a recent study suggest that among older patients, the presence of FLT3-ITD+ may not be of major prognostic value and that allo-SCT should be pursued, when possible, irrespective of initial therapy in older patients with AML, including in those with FLT3-ITD+. (Ref. https://doi.org/10.1182/bloodadvances.2023009748)

Impact of type of induction therapy on outcomes in older adults with AML after allogeneic stem cell transplantation:

Although venetoclax-based lower-intensity regimens have greatly improved outcomes for older adults with AML who are unfit for intensive chemotherapy, the optimal induction for older patients with newly diagnosed AML who are suitable candidates for hematopoietic stem cell transplant (HSCT) is controversial. A single site study analyzed the post HSCT outcomes of 127 patients ≥60 years of age who received induction therapy with intensive chemotherapy (IC; n = 44), lower-intensity therapy (LIT) without venetoclax (n = 29), or LIT with venetoclax (n = 54) and who underwent allogeneic HSCT in the first remission. The 2-year relapse-free survival (RFS) was 60% with LIT with venetoclax vs 54% with IC, and 41% with LIT without venetoclax; the 2-year overall survival (OS) was 72% LIT with venetoclax vs 58% with IC, and 41% with LIT without venetoclax. The benefit of LIT with venetoclax induction was greatest in patients with adverse-risk AML (2-year OS: 74%, 46%, and 29%, respectively). Induction with LIT, with or without venetoclax, was associated with the lowest rate of nonrelapse mortality (NRM) (2-year NRM: 17% vs 27% with IC; P = .04). Using multivariate analysis, the type of induction therapy did not significantly affect any of the post HSCT outcomes evaluated; hematopoietic cell transplantation-specific comorbidity index was the only factor that independently predicted RFS and OS. LIT plus venetoclax followed by HSCT is a feasible treatment strategy in older, fit, HSCT-eligible patients with newly diagnosed AML and may be particularly beneficial for those with adverse-risk disease. (ref: https://doi.org/10.1182/bloodadvances.2022009632)

Phase 2 study of PD-1 blockade following autologous transplantation for patients with AML ineligible for allogeneic transplant

Allogeneic transplant remains the best postremission therapy for patients with nonfavorable risk AML. However, some patients are ineligible because of psychosocial barriers, such as lack of appropriate caregiver support. A phase 2 study of autologous transplantation followed by administration of pembrolizumab (8 cycles starting day +1) was conducted.

Twenty patients with nonfavorable AML in complete remission were treated (median age, 64 years; CR1, 80%); 55% were non-White and adverse-risk AML was present in 40%. Treatment was well tolerated, with only 1 nonrelapse death. Immune-related adverse events occurred in 9 patients. After a median follow-up of 80 months, 14 patients remain alive, with 10 patients in continuous remission. The estimated 2-year LFS was 48.4%, which met the primary end point of 2-year LFS >25%; the 2-year overall survival (OS), nonrelapse mortality, and cumulative incidences of relapse were 68%, 5%, and 46%, respectively. In comparison with a propensity score–matched cohort group of patients with AML receiving allogeneic transplant, the 3-year OS was similar (73% vs 76%). Patients in the study had inferior LFS (51% vs 75%) but superior postrelapse survival (45% vs 14%).

In conclusion, programmed cell death protein–1 blockade after autologous transplant is a safe and effective alternative postremission strategy in patients with nonfavorable risk AML who are ineligible for allogeneic transplant, a context in which there is significant unmet need. (Ref. https://doi.org/10.1182/bloodadvances.2023010477)

ENHANCE 2 study discontinued

Following review by the independent data monitoring committee, Gilead has stopped its ENHANCE 2 study in AML with TP53 mutations as Gilead concluded that magrolimab is unlikely to demonstrate a survival benefit for these patients compared to standard of care. www.gilead.com

ALL

Lenalidomide-associated B-cell ALL: clinical and pathologic correlates and sensitivity to lenalidomide withdrawal

Lenalidomide is an integral component of current therapy for multiple myeloma but carries a risk of secondary malignancies, even in the absence of traditional cytotoxic therapies. This study by Geyer and colleagues examines therapy-related acute lymphoblastic leukemia (ALL) arising in the context of multiple myeloma treated with lenalidomide and highlights the need to understand leukemogenic effects of prolonged lenalidomide maintenance and the potential of lenalidomide to act as a driver even after initiation of lymphoblastic neoplasia. (Ref: https://doi.org/10.1182/bloodadvances.2022009212)

CAR T-cell therapy for adult B-cell ALL: state-of-the-(C)ART and the road ahead

The introduction of CD19 CAR T-cell therapy has revolutionized the field of B-ALL and other CD19+ B-cell malignancies. With the current generation of approved CAR products, we are seeing very encouraging clinical activity in multiply R/R B-ALL. The toxicities associated with CAR T cells are manageable and most institutions have developed clinical practice algorithms to manage these toxicities. The field of CAR T-cell therapy continues to evolve with several novel constructs, novel targets, and combination targets in clinical development, including trials with allogeneic CARs. In the next few years, we expect to see trials incorporating CAR T cells in earlier lines of therapy with the eventual goal of providing long-term disease control for the majority of the patients with B-ALL. (Ref: https://doi.org/10.1182/bloodadvances.2022009462)

Next-generation sequencing–based MRD in adults with ALL undergoing hematopoietic cell transplantation

MRD is an adverse prognostic factor in adult patients with ALL undergoing hematopoietic cell transplant (HCT). Next-generation sequencing (NGS) can detect MRD with a sensitivity of 10–6, but the prognostic value of NGS-based MRD in adult patients with ALL undergoing HCT remains minimally studied. In a recent study, MRD was assessed before HCT (MRDpre) and up to 1 year after HCT (MRDpost). Patients were followed up for leukemia relapse and survival for up to 2 years after HCT. In total, 158 patients had a trackable clonotype for MRD monitoring. The cumulative incidence of relapse was increased at all levels of MRDpre, including in patients who had low MRDpre of <10–4 (hazard ratio [HR], 3.56; 95% confidence interval [95% CI], 1.39-9.15). In multivariable analysis, MRDpre level remained significantly prognostic; however, detectable MRDpost was the strongest predictor of relapse (HR, 4.60; 95% CI, 3.01-7.02). In exploratory analyses limited to patients with B-cell ALL, the detection of post-HCT immunoglobulin H (IgH) MRD clonotypes, rather than non-IgH MRD clonotypes, was associated with relapse. In this analysis across 2 large transplant centers, we found that the detection of MRD by NGS at a level of 10–6 offers significant prognostic value in adults with ALL undergoing HCT. (Ref: https://doi.org/10.1182/bloodadvances.2023009856)

Effect of BMI on toxicities and survival among adolescents and young adults treated on DFCI Consortium ALL trials

Adolescent and young adults (AYAs) with ALL reated with asparaginase-containing pediatric regimens are commonly overweight or obese. A recent study looked at the association of body mass index (BMI) on outcomes of 388 AYAs aged 15 to 50 years treated on Dana-Farber Cancer Institute (DFCI) consortium regimens (2008-2021). BMI was normal in 207 (53.3%) and overweight/obese in 181 (46.7%). Patients who were overweight or obese experienced higher nonrelapse mortality (NRM; 4-year, 11.7% vs 2.8%, P = .006), worse event-free survival (4-year, 63% vs 77%, P = .003), and worse overall survival (OS; 4-year, 64% vs 83%, P = .0001). Because younger (aged 15-29 years) AYAs more frequently had a normal BMI (79% vs 20%, P < .0001), we conducted separate analyses in each BMI group. An excellent OS was found among younger and older (30-50 years) AYAs with normal BMI (4-year OS, 83% vs 85%, P = .89). Conversely, in AYAs who were overweight/obese, worse outcomes were seen in older AYAs (4-year OS, 55% vs 73%, P = .023). Regarding toxicity, AYAs who were overweight/obese experienced higher rates of grade 3/4 hepatotoxicity and hyperglycemia (60.7% vs 42.2%, P = .0005, and 36.4% vs 24.4%, P = .014, respectively) but had comparable rates of hypertriglyceridemia (29.5% vs 24.4%, P = .29). In a multivariable analysis, higher BMI was associated with worse OS, hypertriglyceridemia was associated with improved OS, and age was not associated with OS.

In conclusion, among AYAs treated on DFCI Consortium ALL regimens, elevated BMI was associated with increased toxicity, increased NRM, and decreased OS. The deleterious effect of elevated BMI was more pronounced in older AYAs. (ref: https://doi.org/10.1182/bloodadvances.2023009976)

CAR-T

Longitudinal patient-reported outcomes in patients receiving chimeric antigen receptor T-cell therapy:

A study showed the longitudinal PROs of patients with relapsed/refractory hematologic malignancies, demonstrating a decline in QOL and an increase in depression symptoms early in treatment, followed by an improvement in QOL, psychological distress, and physical symptom burden 3 and 6 months after CAR-T infusion. A significant minority of patients report substantial psychological and physical symptom burdens throughout the treatment trajectory. Our findings highlight the ability of CAR-T to improve PROs and the unmet need for supportive care interventions to ameliorate the QOL, psychological distress, and physical symptoms throughout the continuum of patient experience. (ref: https://doi.org/10.1182/bloodadvances.2022009117)

GvHD

Late acute graft-versus-host disease (GVHD) is defined as de novo acute GVHD presenting beyond 100 days after allogeneic hematopoietic cell transplantation (HCT) without manifestations of chronic GVHD. A recent study has showed:

  • The cumulative incidence of classic acute GVHD that required systemic treatment was 35.2%, and an additional 5.7% of patients required treatment for late acute GVHD.
  • At the onset of symptoms, late acute GVHD was more severe than classic acute GVHD based on both clinical and MAGIC algorithm probability biomarker parameters and showed a lower overall response rate on day 28.
  • Both clinical and biomarker grading at the time of treatment stratified the risk of nonrelapse mortality (NRM) in patients with classic and late acute GVHD, respectively, but long-term NRM and overall survival did not differ between patients with classic and late acute GVHD.
  • Advanced age, female-to-male sex mismatch, and the use of reduced intensity conditioning were associated with the development of late acute GVHD, whereas the use of posttransplant cyclophosphamide–based GVHD prevention was protective mainly because of shifts in GVHD timing.

Because overall outcomes were comparable, the findings, although not definitive, suggest that similar treatment strategies, including eligibility for clinical trials, based solely on clinical presentation at onset are appropriate. (ref: https://doi.org/10.1182/bloodadvances.2023009885)

CAR-T

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a highly effective treatment option for patients with relapsed/refractory large B-cell lymphoma and ALL. However, widespread use is deterred by the development of clinically significant acute inflammatory toxicities, including cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), that induce significant morbidity and require close monitoring. Identification of host biochemical signatures that predict the severity and time-to-onset of CRS and ICANS may assist patient stratification to enable timely mitigation strategies.

A study reports on pretreatment host metabolites that are associated with CRS and ICANS induced by axicabtagene ciloleucel or tisagenlecleucel therapy. Both untargeted metabolomics analysis and validation using targeted assays revealed a significant association between the abundance of specific pretreatment biochemical entities and an increased risk and/or onset of clinically significant CRS (q < .1) and ICANS (q < .25). Higher pretreatment levels of plasma glucose and lower levels of cholesterol and glutamate were associated with a faster onset of CRS. In contrast, low baseline levels of the amino acids proline and glycine and the secondary bile acid isoursodeoxycholate were significantly correlated with clinically significant CRS. Lower concentration of the amino acid hydroxyproline was associated with higher grade and faster onset of ICANS, whereas low glutamine was negatively correlated with faster development of ICANS.

Overall, data indicate that the pretreatment host metabolome has biomarker potential in determining the risk of clinically significant CRS and ICANS, and may be useful in risk stratification of patients before anti-CD19 CAR T-cell therapy. (ref. https://doi.org/10.1182/bloodadvances.2022007456)

MDS

Phase 3 ENHANCE (5F9009) study Magrolimab plus Azacitidine in Higher-Risk MDS: Gilead has announced that this study has been discontinued due to futility based on a planned analysis.

Other

Burnout in US hematologists and oncologists: impact of compensation models and advanced practice provider support

Burnout is a significant challenge in medicine, even more so since the beginning of the COVID-19 pandemic. With this in mind, Lee and colleagues questioned practicing hematologists and oncologists through a survey developed by members of the Fitzhugh Mullan Institute for Health Workforce Equity at George Washington University in collaboration with the American Society of Hematology Recruitment and Retention Working Group. The survey assessed practice activities, career satisfaction, participation in medical education and mentoring, compensation, practice setting, and practitioner demographics. Over one third of survey participants reported burnout. (Ref: https://doi.org/10.1182/bloodadvances.2021006140)

ALAN Patient Preference Study

After almost 2 years of work, our patient preference study is now launched !

UK : Survey link –> click here 

US : Survey link -> click here

France: Survey link –> click here

Spain: Survey link –> click here

Italy: Survey link –> click here

Germany: Survey link –> click here

Background

Obtaining a better understanding of the treatment outcomes that matter to people living with acute leukaemia can be useful to guide drug discovery, inform the appraisal of new treatments, and the development of managed access or outcomes-based payment schemes. To date, however, little quantitative preference research has been conducted in this context. This study could help to inform future treatment reimbursement decisions.

Aims

The overall aim of this study is to better understand the aspects of treatment that matter most to different groups of acute leukaemia patients. This evidence will help inform the evaluation of treatments now and in the future.

More specifically, the objectives are to:

  1. Better understand relative importance of different aspects of leukaemia treatments and their outcomes to individuals with acute leukaemia
  2. Better understand and characterise the heterogeneity in patients’ preferences based on observed patient characteristics
  3. Support future health technology assessments and promote access to future treatment options, based on the aspects that matter most to patients.

Patient profile

  • Age: 18+ y.o
  • All acute leukemias

ALAN is running one study in patients who are relapsed/ refractory and another study in newly diagnosed patients.

Countries

  • UK : Survey link –> click here 
  • US : Survey link -> click here
  • France: Survey link –> click here
  • Spain: Survey link –> click here
  • Italy: Survey link –> click here
  • Germany: Survey link –> click here

LAUNCH: 2023 Global Leukemia Experience Survey

This survey is being run by the Acute Leukemia Advocates Network (ALAN), CLL Advocates Network (CLLAN) and CML Advocates Network (CMLAN).

In 2021-2022, ALAN, CLLAN and CMLAN had ran the first global leukemia experience survey, collecting over 2600 responses from patients and 580 responses from carers around the world. Some results have been presented at conferences as abstracts and posters and we also used those data to shape the 2023 survey.

The questionnaire is about diagnosis, care and treatment for leukemia. Its purpose is to provide information to help us understand the key issues, experiences, and unmet needs for leukemia patients. Our aim is to understand the key issues, experiences and unmet needs for leukemia patients and understand how things are changing/evolving over time.

How you can help?

To achieve our ambition, we are asking for your help. Please can you share the survey link to your leukemia membership, through social media, newsletters and mailing lists.

The more people we can reach, the better the data will be. In order to make the survey as accessible as possible, we translated it in various languages: English, Brazilian Portuguese, Czech, Danish, Dutch, French, German, Hebrew, Italian, Korean, Simplified Chinese, Spanish and Russian.

Who should complete the questionnaire?
This questionnaire can be answered by anyone aged 18 and above directly or indirectly affected by a diagnosis of leukemia, whether this is somebody who has received a diagnosis or who is / has been a carer to someone with a diagnosis. Two question sets have been designed, one for patients, and one for carers. Each of these surveys will take 20 to 30 minutes to complete.

The survey can be accessed using the following link: https://bit.ly/GlobalLeukemiaExperienceSurvey2023

Any questions?

If you have any questions please contact Samantha at samantha@acuteleuk.org

Thank you for your support!

1 month to #WLD23 !

#WLD23 – World Leukemia Day is 3 months away and we prepared a toolkit for you!

This toolkit is designed to encourage various stakeholders involved in World Leukemia Day (e.g., patient advocates, pharmaceutical companies, HCPs, etc.) to use common #WLD23 messages on their social media platforms and websites.

Toolkit –> download it ! World Leukemia Day toolkit 2023

No time or capacity to implement this toolkit? You can still engage your audience by reposting and resharing our posts!

WORLD LEUKEMIA DAY – 4th September 2023

World Leukemia Day on 4th September is a yearly global campaign in collaboration with patient groups across the globe.

It’s the one day of the year people from all around the world can come together to help raise awareness of leukemia. By raising awareness of leukemia and educating the world on the signs and symptoms of the condition, we can work together to help leukemia patients get diagnosed and provide better outcomes for them. You can make a difference no matter who you are and where you live.

Leukemia is the 13th most common cancer in the world. Over 437,000 people are diagnosed with leukemia each year, that’s over 1000 people every day. However, the non-specific signs and symptoms make it difficult to spot. There are over 300,000 deaths caused by leukemia worldwide.

Our campaign is vital because survival rates for leukemia are significantly lower than most common cancers and these rates are worsened by the high rates of emergency diagnosis.

CAMPAIGN

The campaign will continue to address the previous years’ campaign topics, sharing knowledge about signs, symptoms and early detection, and underlining the importance of visiting the doctor when experiencing symptoms.

It will also include contents dedicated to patients, carers, general public and GPs.

KEY MESSAGES

– By raising awareness of leukemia and educating the world on the signs and symptoms of this condition, we can work together to help leukemia patients get diagnosed and provide better outcomes for them. You can make a difference no matter who you are and where you live.

– Encourage people to get seen by a healthcare professional – This will help reduce the numbers of preventable leukemia deaths across the world and provide patients with greater outcomes.

– Healthcare professionals have to be trained to better manage and address potential patients and new diagnosed patients.

HASHTAGS

#BeLeukemiaAware #WLD23 #WorldLeukemiaDay #Leukemia #PatientAdvocacy

MATERIALS

All materials for use can be found on

https://www.worldleukemiaday.org

https://acuteleuk.org/downloads/

Check out all the materials ! WLD23_Materials

SOCIAL MEDIA

A dedicated calendar is prepared from June to September. You can use the prepared posts and/or make your own posts !

Social media calendar –> check it here –> WLD23_Social media plans

June calendar and posts: WLD23_June posts

July calendar and posts: WLD23_July posts

August calendar and posts WLD23_August posts

WLD calendar and posts WLD September posts

Join us on 4th September for World Leukemia Day !

Q2 2023: Additional information and data in acute leukemia

AML

Ipilimumab plus decitabine for patients with MDS or AML in posttransplant or transplant-naïve settings: combination IPI + DEC treatment has an acceptable safety profile and has meaningful clinical activity in patients with R/R MDS/AML that does not appear to require T cell–mediated alloreactivity. IPI + DEC treatment may serve as a less-intensive bridge to transplant among potential transplant candidates. Future studies are warranted to identify rational IPI-based treatment strategies to generate prolonged responses without severe immune toxicity. (Ref: https://doi.org/10.1182/blood.2022017686)

BCL2 Inhibition: A New Paradigm for the Treatment of AML and Beyond: Altering the natural history of AML in unfit and older patients has proved a highly challenging hurdle, despite several decades of concerted clinical trial effort. The arrival of venetoclax (VEN) to the clinical stage represents the most important therapeutic advance to date for older patients with AML. In this review, we will explain how and why VEN works, summarize its remarkable pathway to regulatory approval, and highlight the key milestones that have been important for its successful development in AML. We also provide perspectives on some of the challenges associated with using VEN in the clinic, emerging knowledge regarding mechanisms of treatment failure, and current clinical research directions likely to shape how this drug and others in this new class of anticancer agents are used in the future. (Ref. HemaSphere 7(6):p e912, June 2023. | DOI: 10.1097/HS9.0000000000000912)

Availability of haploidentical donors has broadened utilization of allogeneic hematopoietic cell transplantation (allo-HCT). Peripheral blood stem cells (PBSC) are being used with increased frequency in haploidentical allo-HCT. A study evaluated extent of HLA disparity (2–3/8 versus 4/8 HLA antigen mismatches) on post-allograft outcomes when using T-cell replete PBSC from haploidentical donors for AML in first complete remission. Primary objectives entailed assessing cumulative incidence of grade 2–4 acute graft-versus-host disease (GVHD) and chronic GVHD (any grade). Pertaining to HLA-B leader matching effect, our analysis did not discern any difference in aforementioned post-allograft outcomes for this variable. However, in univariate analysis, absence of an antigen mismatch in HLA-DPB1 showed a trend for better OS. Notwithstanding inherent limitations associated with registry data, the results did not show an advantage of selecting a haploidentical donor with 2–3 of 8 HLA antigen mismatches over one with 4 of 8 HLA antigen mismatches when using PBSC as the cell source. Adverse cytogenetics remains a major adverse determinant of inferior OS and LFS and a higher RI. Using reduced-intensity conditioning yielded worse OS and LFS. (ref. DOI: 10.1097/HS9.0000000000000920)

Pevonedistat with azacitidine in older patients with TP53-mutated AML: a phase 2 study with laboratory correlates: in this phase 2 Beat AML substudy, treatment with AZA + PEVO did not induce responses  in older patients with TP53-mutated AML. These observations mirror recent results with the same combination in myelodysplatic syndrome, stand in contrast to previous results in AML, and do not support the combination as targeted therapy in TP53-mutated AML. Reports of other studies  examining the addition of venetoclax to AZA + PEVO in AML are eagerly awaited. (Ref. https://doi.org/10.1182/bloodadvances.2022008625)

ALL

Haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide (PTCy) graft-versus-host-disease (GVHD) prophylaxis yields a similar OS to HLA-matched unrelated donor (MUD) HCT with conventional prophylaxis. A study showed that despite a higher risk of relapse, younger donor haploidentical HCT with PTCy prophylaxis may be preferred over older MUD HCT with conventional prophylaxis in patients with ALL due to lower NRM and better OS. Further analysis comparing the effect of donor age in haploidentical PTCy vs MUD PTCy is warranted. (Ref. https://doi.org/10.1182/bloodadvances.2022009240)

Glucocorticoids are extensively used for the treatment of ALL as they pressure cancer cells to undergo apoptosis. Nevertheless, glucocorticoid partners, modifications, and mechanisms of action are hitherto poorly characterized. Ongoing research suggests that a better understanding of GR nuclear functions and cofactors in ALL and use of inhibitors against epigenetic cofactors or enzymes controlling posttranslational modifications in combination with GCs could be of therapeutic value in high-risk ALL cases. (Ref. DOI: 10.1097/HS9.0000000000000916)

High-risk Combinations of Additional Chromosomal Abnormalities in Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia: JALSG Ph+ALL TKI-SCT Study: Additional chromosomal abnormalities (ACAs) are found in 60%–70% of Philadelphia chromosome-positive ALL (Ph+ALL) cases. the coexistence of +der(22)t(9;22) and a complex karyotype was identified as a high-risk combination of ACAs in Ph+ALL. Multiple ACAs are often observed in Ph+ALL, leading to identifying this subgroup with a poor prognosis. It was characterized by early relapse, although remission could be achieved at the same rate as standard-risk Ph+ALL. Further molecular genetic elucidation and the establishment of effective therapeutic strategies are warranted. (Ref. HemaSphere 7(6):p e899, June 2023. | DOI: 10.1097/HS9.0000000000000899)

To determine the prognostic significance of central nervous system leukemic involvement in newly diagnosed T-cell T-ALL, outcomes on consecutive, phase 3 clinical trials were examined. (Ref: https://doi.org/10.1182/blood.2022018653)

Key findings:

  • Patients with CNS-1 and CNS-2 status have similar outcomes across 2 large studies with divergent therapies, including with and without CRT.
  • Patients with CNS-3 T-ALL treated with nelarabine had similar OS as CNS-1 and CNS-2, and thus should receive nelarabine as standard of care.
CAR-T

Treatment of CAR-T cell toxicities –> read here