Vesanoid (tretinoin) / Roche - LARVOL DELTA

Arsenic Trioxide and All-Trans Retinoic Acid Combination Therapy for the Treatment of High-Risk Acute Promyelocytic Leukemia: Results From the APOLLO Trial. (PubMed, J Clin Oncol) - P3 | "The results of the APOLLO trial support the use of ATO and ATRA for the treatment of newly diagnosed patients with high-risk APL."

Journal • Acute Promyelocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology

Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia (clinicaltrials.gov) - P3 | N=158 | Active, not recruiting | Sponsor: Children's Oncology Group | Trial completion date: Sep 2025 ➔ Jun 2029

Trial completion date • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • PML • RARA

All-Trans Retinoic Acid (ATRA) and Atezolizumab for the Treatment of Recurrent or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Dwight Owen | Trial completion date: Jan 2026 ➔ Dec 2026

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • PD-L1

Long-term follow-up of a phase 2 study of all-trans retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin in acute promyelocytic leukemia. (PubMed, Cancer) - P2 | "The combination of ATO-ATRA and GO was curative in 94% of patients who had APL with a favorable safety profile (ClinicalTrials.gov identifier NCT01409161)."

Journal • P2 data • Acute Promyelocytic Leukemia • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Oncology

FIRST RESULTS OF THE APOLLO TRIAL: A RANDOMIZED PHASE III STUDY TO COMPARE ATO COMBINED WITH ATRA VERSUS STANDARD AIDA REGIMEN FOR PATIENTS WITH NEWLY DIAGNOSED, HIGH-RISK ACUTE PROMYELOCYTIC LEUKEMIA (EHA 2024) - "Background: Pioneered by the APL0406 trial (Lo-Coco et al., NEJM 2013), prior investigations have demonstrated the superiority of combining all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) over standard ATRA and chemotherapy (CHT) as front-line management of low/intermediate risk acute promyelocytic leukemia (APL)...Death in CR/CRi were observed in 0 and 3 pts in the ATRA-ATO and ATRA-CHT arm, respectively... First-line therapy with ATRA-ATO with two initial doses idarubicin results in superior EFS compared to conventional ATRA-CHT in patients with HR-APL. Further analysis of the APOLLO trial may support the implementation of this regimen as the new standard of care in patients with HR-APL"

Clinical • P3 data • Acute Promyelocytic Leukemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Septic Shock • Thrombosis

All-Trans Retinoic Acid (ATRA) and Atezolizumab for the Treatment of Recurrent or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Dwight Owen | Trial primary completion date: Jan 2026 ➔ Sep 2025

Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • PD-L1

Evaluation of ATRA Activity in Combination With Anastrozole in Pre-operative Phase of Operable Early Breast Cancer (clinicaltrials.gov) - P2 | N=76 | Terminated | Sponsor: Mario Negri Institute for Pharmacological Research | N=112 ➔ 76 | Trial completion date: Sep 2024 ➔ Jan 2025 | Recruiting ➔ Terminated | Trial primary completion date: Aug 2024 ➔ Jan 2025; Low enrolment rate

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Acute leukemia during pregnancy: A three-decade Mayo Clinic experience (ASH 2025) - "One patient had refractory disease and achieved partial remission after salvage,another had refractory disease and achieved CR after multiple lines of therapy, and a third achieved CRafter FLAG-idarubicin and revumenib...All receivedintensive induction: 7+3 (n=5), 7+3 + ATRA (n=1), 7+3 + gilteritinib (n=1), and 7+3 + nilotinib (n=1)...Notably, 5 (28%) of patients received chemotherapy during pregnancy. Larger,multi-institutional cohorts are warranted to further characterize the incidence and outcomes of AL inpregnancy."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Leukemia • Lymphoma • Pneumonia • Respiratory Diseases • T Acute Lymphoblastic Leukemia • KMT2A • NUP214

Tretinoin and Arsenic Trioxide With or Without Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia (clinicaltrials.gov) - P2 | N=151 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Trial completion date • Trial primary completion date • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • PML • PRAM1 • RARA

Comparative long-term cardiovascular and hematologic outcomes of gemtuzumab ozogamicin containing regimens versus idarubicin containing regimens in acute promyelocytic leukemia: A propensity-matched analysis of real-world multicenter data (ASH 2025) - "Conclusions In this real-world, propensity-matched analysis of APL patients, ATRA + GO was associated with significantly lower 5-year mortality and incidence of cardiac arrest but increased risks of DIC compared to ATRA + idarubicin. These findings highlight the importance of individualized risk-benefit assessment when selecting induction regimens for APL."

Clinical • Real-world • Real-world evidence • Acute Promyelocytic Leukemia • Asthma • Atrial Fibrillation • Congestive Heart Failure • Diabetes • Endocrine Disorders • Heart Failure • Hematological Malignancies • Hypertension • Immunology • Ischemic stroke • Leukemia • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • Thrombosis • CD33

Clinical characteristics and prognosis of therapy-related hematological neoplasms: A single-center retrospective study (ASH 2025) - "One patient with therapy-related acute promyelocytic leukemia (t-APL) achieved CR with ATO+ATRA targeted therapy... t-HN is a rare group of hematologic malignancies secondary to prior solid or hematologic cancers, closely associated with the type and cumulative dose of cytotoxic agents, as well as the intensity and dose of radiotherapy. t-HN frequently harbors cytogenetic abnormalities, exhibits poor treatment response, and is associated with short median survival. Clinicians must carefully select cytotoxic regimens for cancer patients, weighing treatment benefits against the risk of developing t-HN."

Retrospective data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Breast Cancer • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Lung Cancer • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Solid Tumor • ABL1 • BCR • KMT2A

Outcomes with ATO/ATRA based regimen in apml - steroid induced toxicities are a concern in LMICs (ASH 2025) - "A total of 149 patients were included (mean age 36 ± 13 years, 60.4% male), 110 received ATRA/ATO withor without chemotherapy (study cohort) and 39 received ATRA and ATO alone. In the study cohort, 80%were low-intermediate risk and 88.1% achieved complete remission following induction. Inductionmortality was 5.45% (6/110), and were due to infections (n=3), coagulopathy (n=1), and differentiationsyndrome (n=2)."

Acute Promyelocytic Leukemia • Diabetes • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia

Salvage-free, transplantation-free survival (STFS) in AML: Proposition for a novel clinical endpoint to better assess the efficacy of novel drugs in combination with intensive chemotherapy. a dataml registry study. (ASH 2025) - "Inclusion criteria for the APL cohort(used as control): ≥18y, between 01/2010 and 12/2022, first-line treatment including arsenic trioxide(ATO) and ATRA. The impact of trulyeffective first-line treatment is illustrated in APL patients, who previously had a similar prognosis to otherAML patients before the era of PML-RARA directed therapies. Improving STFS should become a keyobjective in clinical trials assessing new targeted agents in combination with IC in AML."

Clinical • Combination therapy • IO biomarker • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Transplantation • BCL2 • FLT3 • IDH1 • IDH2 • KMT2A • NPM1 • PML

Real-world insights into ATRA-based maintenance therapy and prognostic markers of relapse in acute promyelocytic leukemia (ASH 2025) - "We aimed to evaluate thelong-term clinical impact of ATRA-based maintenance therapy and other prognostic factors of relapse in amulticenter real-world cohort of Korean APL patients treated with ATRA+Idarubicin (AIDA) protocol.We retrospectively analyzed 286 APL patients who achieved complete remission following AIDA-basedchemotherapy from 2002–2024 across five South Korean tertiary centers...Key prognostic variables including maintenance therapy, Sanz risk, MRD, FLT3mutation status, and sex were assessed.252 patients (88.1%) received maintenance following consolidation, whereas 34 patients (11.9%) did not.Among those who received maintenance, 210 patients (73.4%) were treated with ATRA alone, while 42patients (14.7%) received ATRA in combination with low-dose chemotherapy (6-mercaptopurine andmethotrexate)...Post-consolidation MRD positivity emerged as the most significant predictor of relapse in APL, whileATRA-based maintenance therapy did not confer a significant..."

Biomarker • Clinical • Real-world • Real-world evidence • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • FLT3

Central nervous system relapse in acute promyelocytic leukemia in the arsenic era: A case series and review of emerging evidence (ASH 2025) - "Background :Acute Promyelocytic Leukemia (APML) is highly curable with all-trans retinoic acid (ATRA) andarsenic trioxide (ATO)...Treated with ATO/ATRA, intrathecal therapy, high-dose cytarabine(HiDAC), craniospinal radiotherapy in preparation for autologous transplant...Standard induction agents like ATRA, ATO, and idarubicin have limited CNS penetration.Studies suggest that HiDAC and prophylactic intrathecal therapy during consolidation mayreduce CNS relapse risk, as shown in the APL 2000 trial.CNS relapse in APML remains a rare but challenging clinical entity in the ATO era...CNS relapse in APML remains a rare but challenging clinical entity in the ATO era. Risk factorsmay include FLT3-ITD mutation, prior CNS hemorrhage, and high-risk disease features. Our caseshighlight the importance of early neurologic assessment and raise consideration for CNS-directedprophylaxis in select high-risk patients.Notably, ATO/ATRA is now available for the treatment of high-risk APML in..."

Clinical • Review • Acute Promyelocytic Leukemia • CNS Disorders • Hematological Disorders • Hematological Malignancies • Leukemia • FLT3

Fertility and Parenthood in Patients with Acute Promyelocytic Leukemia Treated with Arsenic Trioxide and All-Trans Retinoic Acid (ASH 2023) - "Patients with intermediate and high-risk APL also received maintenance therapy for 1 year with ATRA, 6 Mercaptopurine and Methotrexate. CONCLUSION All patients (male and female) who wanted to conceive children were able to successfully conceive and bear children post therapy for APL in our study. ATO and ATRA can safely be used for the treatment of patients with APL and appears to have little, if any, impact on long term fertility."

Clinical • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Long-Term Outcome of 1296 Patients with Newly Diagnosed with APL: A Harmony Alliance Study (ASH 2023) - "Background: APL, a rare and aggressive subtype of acute myeloid leukemia (AML), is now curable in 75-90% of patients using targeted agents [All-trans retinoic acid (ATRA)/Arsenic Trioxide (ATO) or ATRA combined with chemotherapy (ATRA+Idarubicin, AIDA-based)]. The analysis at long-term of the Harmony APL registry confirmed that patients treated with the ATRA-ATO chemo-free regimen present a significant survival advantage vs the AIDA regimen, with reduced ED rates and prolonged OS, independent of Sanz-risk score. Patients enrolled in clinical trials presented improved survival both in AIDA and in ATRA-ATO cohorts."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Largest Real-World Evaluation of Treatment Regimens and Clinical Outcomes Among Patients with Acute Promyelocytic Leukemia in the US: Data from the Command Consortium (ASH 2024) - "Chemotherapy-free protocols consisting of arsenic trioxide (ATO) and ATRA have become the standard of care for low-risk APL with high cure rates and reduced hematologic toxicities...At least 1 dose of gemtuzumab ozogamicin was given to 58 (14%) pts, of which 35 (60%) were considered high risk...Outcomes for this disease remain extremely positive, with low 30-day mortality rates noted in this study along with durable OS rates and low incidence of relapse. Additional information on outcomes, safety, and supportive care will be presented at the meeting."

Clinical • Clinical data • HEOR • Real-world • Real-world evidence • Acute Promyelocytic Leukemia • Cardiovascular • Diabetes • Hematological Malignancies • Leukemia • Metabolic Disorders • Oncology • Thrombosis • FLT3 • KRAS • NRAS • WT1

Impact of Arsenic Trioxide in the Treatment of Higher Risk Acute Promyelocytic Leukemia (ASH 2023) - "Eighty-five patients received corticosteroid prophylaxis (81 (95%) with Dexamethasone and 5 (5%) with Prednisolone)...All patients treated with ATO were cytoreduced: 7 with Hydroxyurea (14%), 17 with Idarubicin (34%) and 26 with both (52%)... The survival outcomes were significantly poorer in high-risk APL patients treated without ATO during induction, regardless of the cytoreduction strategy. The toxicity profile of ATO was acceptable. Combining ATO and ATRA limits the use of cytotoxic chemotherapy, which could reduce myelosuppression and long-term complications such as cardiotoxicity and secondary myeloid neoplasms."

Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Septic Shock

Prognostic Impact of Complex Karyotype in Acute Promyelocytic Leukemia (ASH 2024) - "Arsenic trioxide (ATO) or chemotherapy plus all-trans retinoic acid (ATRA) frontline treatment regimens are the current standard of care (SOC) for patients with newly diagnosed APL (Sanz et al., 2019)...All patients received treatment, 93 (62.8%) with chemotherapy (idarubicin 12mg/m 2) plus ATRA and 55 (37.2%) with ATO plus ATRA...As therapeutical decisions are based on the initial prognostic risk assessment, the inclusion of CK as a variable in this assessment may provide more precise prognostic information and may indicate a need for better treatment strategies to overcome this adverse effect and improve outcomes in this subgroup of patients. Larger prospective analyses are required to confirm our data."

Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Therapy Based on Attenuated Arsenic Trioxide Plus Low-Dose All-Trans-Retinoic Acid in Acute Promyelocytic Leukemia. Is Less More? (ASH 2024) - P1/2 | "If high-risk (WBC >10 x109/L at presentation) a mitoxantrone 10 mg/m2/day was added on day 1...Differentiation syndrome (DS) prophylaxis with dexamethasone and hydroxyurea or anthracycline was used; supportive transfusion care as needed to reach goals...Despite ATO and ATRA ED remains the main problem in our context. This therapy was effective and safe, even for outpatient use after the late induction phase. This approach is promising, although further follow-up and validation studies are needed to confirm our results."

Acute Kidney Injury • Acute Promyelocytic Leukemia • CNS Disorders • Gastroenterology • Infectious Disease • Metabolic Disorders • Nephrology • Renal Disease • PML

Improved Real-World Outcomes of Patients with Acute Promyelocytic Leukemia Treated with First-Line Arsenic Trioxide in Specialized Centers in Portugal through a 24/7 Phone-Based Referral: A Study from the Portuguese Acute Leukemia Group (ASH 2024) - "All patients with genetically confirmed APL who received first-line ATO plus ATRA between January 2017 and May 2024 were included, regardless of disease risk. Despite low numbers, our data support the universal use of DS prophylaxis and first-line ATO's applicability in high-risk patients, who also benefited from this regimen. Through quick initiation of treatment with the effective ATRA + ATO combination, we showed a considerable improvement in the ED rate in 2017-2024, which is a third of the 11.4% ED rate previously reported by our group in a non-high risk APL cohort treated with ATRA + chemotherapy from 2010 to 2017."

Clinical • Real-world • Real-world evidence • Acute Promyelocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Septic Shock

All-Trans Retinoic Acid (ATRA) and Atezolizumab for the Treatment of Recurrent or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Dwight Owen | Suspended ➔ Active, not recruiting | Trial completion date: Oct 2025 ➔ Jan 2026 | Trial primary completion date: Oct 2025 ➔ Jan 2026

Enrollment closed • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • PD-L1

Longitudinal analysis of intestinal microbiota in patients with acute leukemia- on behalf of the translational research project Harmonized prospective asservation and anlaysis of biomaterial in AML (HARPOON), granted by the Bavarian Center for Cancer Research (BZKF) (DGHO 2025) - "ATO/ATRA.4 pts. also received midostaurin...with CML blast crisis receiving IC with "7+3" + dasatinib.As a result, we are currently performing a cross-sectional and longitudinal analysis in paired, longitudinally acquired fecal samples/serum of 35 AML and ALL patients receiving therapy at UKR to(1) associate microbiome (metagenomic sequencing)/metabolite data (targeted metabolomics) with respective clinical data [applied antibiotics, infections, applied induction therapy, remission, and relapses] and(2) demonstrate feasibility.Conclusion and future milestones: Biobanking in patients with newly diagnosed AL is feasible. Microbiome biobanking has now been successfully established for pts. with AL at UKR and harmonization of this process at all BZKF partner site is ongoing.At UKR, a total number of 181 fecal samples/serum have been recruited of(1) 25 pts. with AML; Of those, 12 pts."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Leukemia • Oncology

Concurrent Primary Sclerosing Cholangitis and Acute Promyelocytic Leukemia: A Rare Case Report (ACG 2025) - "Biopsy of the L5 lesion confirmed myeloid sarcoma, and the patient was started on arsenic trioxide and all-trans retinoic acid (ATO+ATRA). Imaging showed progression of PSC with increased peripheral biliary dilation and multifocal intrahepatic and extrahepatic biliary strictures, along with wall thickening and enhancement, raising concern for ATRA-related PSC progression. This case highlights a rare concurrence of PSC and APL, raising the question of a possible association between the two diseases. The observed PSC progression following APL diagnosis and treatment presents a clinical dilemma: whether the progression was drug-induced or simply reflects the natural course of PSC.Figure: MRI showing a new enhancing lesion at the T12 vertebra, concerning for myeloid sarcoma in a patient with acute promyelocytic leukemia."

Case report • Clinical • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Fatigue • Fibrosis • Hematological Malignancies • Hepatology • Immunology • Leukemia • Movement Disorders • Sarcoma • Solid Tumor