The first 60 days: Higher-risk myelodysplastic syndromes

Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.

These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.

• Medical oncologistNamed in the standard of care for: Transplant candidate, Not a transplant candidate, Failure of hypomethylating therapy.
• Transplant and cell therapy teamNamed in the standard of care for: Transplant candidate.
• Palliative and supportive care teamNamed in the standard of care for: Failure of hypomethylating therapy.

A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.

Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.

1. 1.Transplant candidateNCCN Guidelines: Myelodysplastic Syndromes

   Allogeneic stem cell transplant after donor search, usually with azacitidine or decitabine to bridge and reduce blasts; reduced-intensity conditioning in older patients.

   Allogeneic stem cell transplantationAzacitidineDecitabineConditioning regimen (myeloablative, reduced-intensity)Trial of Orca-T Following Reduced Intensity or Nonmyeloablative Conditioning in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
2. 2.Not a transplant candidateNCCN Guidelines: Myelodysplastic Syndromes

   Azacitidine (AZA-001) or decitabine, or oral decitabine-cedazuridine, continued until progression; trials of hypomethylating agent combinations.

   AzacitidineDecitabineDecitabine + cedazuridine (oral)Hypomethylating agents (azacitidine, decitabine)A Study Comparing Treatment Preference Between Oral Decitabine/Cedazuridine and Azacitidine in Myelodysplastic Syndrome, Low-Blast Acute Myeloid Leukemia, or Chronic Myelomonocytic Leukemia
3. 3.Failure of hypomethylating therapyNCCN Guidelines: Myelodysplastic Syndromes

   Clinical trial; venetoclax combinations off-label in selected patients; genotype-directed drugs where IDH, FLT3 or KMT2A targets exist; best supportive care.

   VenetoclaxIvosidenibRevumenibTransfusion support and anaemia managementA Study of CTX-712 in Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes

Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.

Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.

• A Study Comparing Treatment Preference Between Oral Decitabine/Cedazuridine and Azacitidine in Myelodysplastic Syndrome, Low-Blast Acute Myeloid Leukemia, or Chronic Myelomonocytic LeukemiaPhase 3 · active · NCT05883956A Phase 3b, Randomized, Open-Label, Double Crossover Study Comparing Treatment Preference Between Oral Decitabine/Cedazuridine and Azacitidine in Adult Patients With IPSS R Intermediate Myelodysplastic Syndrome, Low Blast Acute Myeloid Leukemia, IPSS Intermediate-2 or High Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
• Study to Evaluate Imetelstat in Patients With High-Risk MDS or AML Failing HMA-based TherapyPhase 2 · active · NCT05583552A Phase II Study Evaluating the Efficacy and Safety of Imetelstat in Patients With HR Myelodysplastic Syndromes or AML Failing HMA-based Therapy
• Trial of Orca-T Following Reduced Intensity or Nonmyeloablative Conditioning in Patients With Acute Myeloid Leukemia or Myelodysplastic SyndromePhase 2 · recruiting · NCT07216443A Phase 2 Trial of Orca-T Following Reduced Intensity or Nonmyeloablative Conditioning in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
• A Study of CTX-712 in Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic SyndromesPhase 1/2 · recruiting · NCT05732103Phase 1/2 Multicenter, Open-Label Study of CTX-712 in Patients With Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes
• First-in-human Study Aiming to Characterize the Safety, Tolerability, Pharmacokinetic and Preliminary Signs of Activity of ABD-3001 in Refractory or Relapsed AML and High Risk MDS Adult PatientsPhase 1/2 · recruiting · NCT05601726First-In-Human, Open Label, Dose Escalation Study to Evaluate Safety, PK and PD of ABD-3001 As Monotherapy in Relapsed/Refractory Acute Myeloid Leukemia or High/Very-high Risk Myelodysplastic Syndromes Patients, Ineligible for Intensive or New Generation Targeted Therapy.

Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.

• Free in oncologyFree testing, helplines, rides and lodging, second opinions and trial travel help, with who is eligible.
• Financial helpManufacturer programmes, national schemes and charities by country and product.
• Second opinionExpert centres for this cancer in your country and how referral works.

• Higher-risk myelodysplastic syndromes: the full pageHigher-risk myelodysplastic syndromes behave like a slow leukaemia and often become one. Azacitidine lengthens life and a donor stem cell transplant is the only cure; every attempt to improve on azacitidine in a large trial, including the venetoclax combination tested in VERONA, has so far failed.
• One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
• Treatment sequencingWhich treatment tends to follow which, line by line.
• NavigatorStandard of care for your stage, what you have tried, and trials near you.