Illustrative case vignettes highlighting key concepts of IWG 2023 MDS response criteria
| Key concept . | Case vignette . |
|---|---|
| Case 1: lowering of Hb threshold for CR definition | A patient with HR-MDS and a baseline of 8% BM blasts, Hb 8.5 g/dL, platelets 30 × 109/L, and ANC 0.4 × 109/L is being treated with azacitidine. After cycle 2 of treatment, BM blasts are 3%, Hb 10.2 g/dL, platelets 110 × 109/L, and an ANC of 1.9 × 109/L. At time of response assessment, the patient has no PB blasts and has not received any transfusions or growth factors for 4 wk. Per the IWG 2023 MDS criteria, the response would be classified as CR. |
| Case 2: “less-than-CR” response | A patient with 9% BM blasts at baseline, Hb 7.5 g/dL, platelets 105 × 109/L requiring intermittent transfusions, and ANC 0.3 × 109/L is being treated with azacitidine. After cycle 4 of treatment, BM blasts are 2%, Hb 10.4 g/dL, platelets 120 × 109/L, and an ANC of 0.5 × 109/L. The patient has not received any transfusions or growth factors for 3 wk. Per IWG 2023 MDS criteria, this would be classified as CRL, specifically CRbi. Of note, baseline PB cell counts do not affect assessment of CR, CRL, CRh, or PR but are relevant to the definition of HI per the IWG 2018 MDS criteria. |
| Case 3: distinction of CRL vs CRh | Patient A had a baseline Hb 8.0 g/dL, platelets 25 × 109/L, an ANC of 0.2 × 109/L, and BM blast count of 7%. At response assessment, Hb level was 10.2 g/dL, platelet count was 30 × 109/L, and ANC was 0.3 × 109/L, with BM blast percentage of 3%. Patient B has a baseline Hb of 9.0 g/dL, platelet count of 25 × 109/L, an ANC of 0.4 × 109/L, and BM blast percentage of 10%. At response assessment, Hb is 9.2 g/dL, platelets and ANC have improved to 55 × 109/L and 0.8 × 109/L, respectively, with BM blast percentage of 3%. Both patients have no PB blasts and have not received any transfusions or growth factors for 2 wk before response assessment. Per IWG 2023 MDS criteria, patient A would be classified as CRL, specifically CRuni(erythroid lineage) and patient B as CRh. |
| Case 4: ORR | A patient is treated with azacitidine and an investigational agent on clinical trial. From a baseline of 7% BM blasts, Hb 8.0 g/dL, platelets 28 × 109/L, and an ANC of 0.4 × 109/L, his best response after 2 cycles of treatment shows 3% BM blasts, Hb 7.5 g/dL, platelets 20 × 109/L, and an ANC of 0.2 × 109/L, with no PB blasts. Per IWG 2006 criteria, the patient would be scored as a mCR. Per the clinical trial protocol, the primary end point is a composite of CR + mCR + PR and therefore this patient would be included as a responder. Per IWG 2023 MDS criteria, ORR should be defined as a composite of CR (or CR equivalent) + PR + CRL+ CRh + HI and therefore the response of this patient would not be included in the ORR. |
| Case 5: molecular and cytogenetic response | A patient had a baseline BM blast count of 8%, Hb 7.2 g/dL, platelets 32 × 109/L, and ANC 0.2 × 109/L. The patient has deletion 20q and an IDH1 mutation at a VAF of 40% by a central NGS panel. The patient is enrolled on a clinical trial and achieves a CR according to IWG 2023 MDS criteria after 3 cycles of investigational treatment. Additional data from the time of response show a normal karyotype with disappearance of the IDH1 mutation using the same panel. Per IWG 2023 MDS criteria, the patient would additionally be classified as achieving the provisional MRD-negative response. |
| Case 6: disease progression and CR equivalent | A patient with HR-MDS has baseline 4% BM blasts, Hb 6.5 g/dL, platelets 20 × 109/L, and ANC 0.3 × 109/L. The patient also had monosomy 7 in 14/20 cells and a TP53 mutation with a VAF of 35% by NGS. The patient is treated on a clinical trial using azacitidine in combination with an investigational agent. After cycle 2 of treatment, BM blasts are 7%, the patient remains profoundly cytopenic and monosomy 7 is seen in 10/20 cells. After cycle 3, Hb is 11.2, platelets 105 × 109/L, and ANC 1.1 × 109/L. At the time of response assessment, the patient has no PB blasts and has not received any transfusions or growth factors for 3 wk before the response assessment. BM assessment after cycle 3 shows 2% BM blasts, with no evidence of monosomy 7 by karyotype or fluorescence in situ hybridization. However, the TP53 mutation persists at a VAF of 25% by NGS. Per IWG 2006 criteria, the patient would have met criteria for PD based on increase in blasts by 50% or more for a patient with <5% baseline BM blasts (from 4% to 7%) and would have been taken off trial. After cycle 3, based on blasts below 5% in marrow and complete blood count within CR range, patient would be recorded as CR. Per IWG 2023 MDS criteria, the response would not be classified as PD after cycle 2 solely based on transient increases in BM blasts of <5% and having no other clear evidence of disease progression. After 3 cycles, the response would be reported as CR equivalent as the patient had trilineage count recovery with full disappearance of the cytogenetic abnormity. As the baseline BM blast count was <5%, the patient is not evaluable for CR. |
| Case 7: disease relapse | A patient with HR-MDS is treated with azacitidine monotherapy and achieves a CR after cycle 4. He continues on azacitidine for another 3 cycles when he is noted to have a decrease in his Hb from 11.2 g/dL at best response to 9.5 × 109/L in the setting of an upper gastrointestinal tract bleed. After endoscopy, his Hb improves back to 11.5 g/dL. Per the IWG 2006 MDS criteria, such a transient decline in Hb would be classified as disease relapse. Per IWG 2023 MDS criteria, this would not be classified as disease relapse because of the transient nature of worsening anemia in the setting of a concurrent illness. |
| Case 8: time-to-event outcomes | A patient with HR-MDS with severe pancytopenia and 9% BM blasts is enrolled in a single-arm, phase 2 clinical trial, which investigates a novel combination of a HMA + an investigational agent. The trial uses EFS as the primary end point. After 3 mo of therapy, the patient continues to be deeply pancytopenic and a BM assessment shows 6% blasts. The investigator is deciding whether this situation constitutes failure of therapy as it is not addressed in the clinical trial protocol. EFS per the IWG 2006 criteria is defined as “failure or death from any cause” without providing an explicit definition of “failure”.16 Per IWG 2023 MDS criteria, an event would be defined as (1) PD; (2) failure to achieve CR (or CR equivalent), PR, CRL, CRh, or HI within 6 mo of study entry; (3) Relapse from CR (or CR equivalent), PR, CRL, CRh + HI; or (4) death from any cause. Per IWG 2023 criteria, this patient did not experience a “failure” event and is still within the 6-mo window during which HMA-based therapy can still lead to an objective response, and therefore, can continue on-trial therapy unless protocol explicitly recommends otherwise. |
| Case 9: SD | A patient with a baseline of 6% BM blasts, Hb 9.0 g/dL, platelets 55 × 109/L, and ANC 1.3 × 109/L notes subjective improvement in his quality of life with treatment despite no change in peripheral blood counts or BM blast counts. By IWG 2006 criteria, the patient is classified as SD. Per IWG 2023 MDS criteria, SD is not recognized as a formal response, and if SD is noted, it should not be included in the ORR. |
| Key concept . | Case vignette . |
|---|---|
| Case 1: lowering of Hb threshold for CR definition | A patient with HR-MDS and a baseline of 8% BM blasts, Hb 8.5 g/dL, platelets 30 × 109/L, and ANC 0.4 × 109/L is being treated with azacitidine. After cycle 2 of treatment, BM blasts are 3%, Hb 10.2 g/dL, platelets 110 × 109/L, and an ANC of 1.9 × 109/L. At time of response assessment, the patient has no PB blasts and has not received any transfusions or growth factors for 4 wk. Per the IWG 2023 MDS criteria, the response would be classified as CR. |
| Case 2: “less-than-CR” response | A patient with 9% BM blasts at baseline, Hb 7.5 g/dL, platelets 105 × 109/L requiring intermittent transfusions, and ANC 0.3 × 109/L is being treated with azacitidine. After cycle 4 of treatment, BM blasts are 2%, Hb 10.4 g/dL, platelets 120 × 109/L, and an ANC of 0.5 × 109/L. The patient has not received any transfusions or growth factors for 3 wk. Per IWG 2023 MDS criteria, this would be classified as CRL, specifically CRbi. Of note, baseline PB cell counts do not affect assessment of CR, CRL, CRh, or PR but are relevant to the definition of HI per the IWG 2018 MDS criteria. |
| Case 3: distinction of CRL vs CRh | Patient A had a baseline Hb 8.0 g/dL, platelets 25 × 109/L, an ANC of 0.2 × 109/L, and BM blast count of 7%. At response assessment, Hb level was 10.2 g/dL, platelet count was 30 × 109/L, and ANC was 0.3 × 109/L, with BM blast percentage of 3%. Patient B has a baseline Hb of 9.0 g/dL, platelet count of 25 × 109/L, an ANC of 0.4 × 109/L, and BM blast percentage of 10%. At response assessment, Hb is 9.2 g/dL, platelets and ANC have improved to 55 × 109/L and 0.8 × 109/L, respectively, with BM blast percentage of 3%. Both patients have no PB blasts and have not received any transfusions or growth factors for 2 wk before response assessment. Per IWG 2023 MDS criteria, patient A would be classified as CRL, specifically CRuni(erythroid lineage) and patient B as CRh. |
| Case 4: ORR | A patient is treated with azacitidine and an investigational agent on clinical trial. From a baseline of 7% BM blasts, Hb 8.0 g/dL, platelets 28 × 109/L, and an ANC of 0.4 × 109/L, his best response after 2 cycles of treatment shows 3% BM blasts, Hb 7.5 g/dL, platelets 20 × 109/L, and an ANC of 0.2 × 109/L, with no PB blasts. Per IWG 2006 criteria, the patient would be scored as a mCR. Per the clinical trial protocol, the primary end point is a composite of CR + mCR + PR and therefore this patient would be included as a responder. Per IWG 2023 MDS criteria, ORR should be defined as a composite of CR (or CR equivalent) + PR + CRL+ CRh + HI and therefore the response of this patient would not be included in the ORR. |
| Case 5: molecular and cytogenetic response | A patient had a baseline BM blast count of 8%, Hb 7.2 g/dL, platelets 32 × 109/L, and ANC 0.2 × 109/L. The patient has deletion 20q and an IDH1 mutation at a VAF of 40% by a central NGS panel. The patient is enrolled on a clinical trial and achieves a CR according to IWG 2023 MDS criteria after 3 cycles of investigational treatment. Additional data from the time of response show a normal karyotype with disappearance of the IDH1 mutation using the same panel. Per IWG 2023 MDS criteria, the patient would additionally be classified as achieving the provisional MRD-negative response. |
| Case 6: disease progression and CR equivalent | A patient with HR-MDS has baseline 4% BM blasts, Hb 6.5 g/dL, platelets 20 × 109/L, and ANC 0.3 × 109/L. The patient also had monosomy 7 in 14/20 cells and a TP53 mutation with a VAF of 35% by NGS. The patient is treated on a clinical trial using azacitidine in combination with an investigational agent. After cycle 2 of treatment, BM blasts are 7%, the patient remains profoundly cytopenic and monosomy 7 is seen in 10/20 cells. After cycle 3, Hb is 11.2, platelets 105 × 109/L, and ANC 1.1 × 109/L. At the time of response assessment, the patient has no PB blasts and has not received any transfusions or growth factors for 3 wk before the response assessment. BM assessment after cycle 3 shows 2% BM blasts, with no evidence of monosomy 7 by karyotype or fluorescence in situ hybridization. However, the TP53 mutation persists at a VAF of 25% by NGS. Per IWG 2006 criteria, the patient would have met criteria for PD based on increase in blasts by 50% or more for a patient with <5% baseline BM blasts (from 4% to 7%) and would have been taken off trial. After cycle 3, based on blasts below 5% in marrow and complete blood count within CR range, patient would be recorded as CR. Per IWG 2023 MDS criteria, the response would not be classified as PD after cycle 2 solely based on transient increases in BM blasts of <5% and having no other clear evidence of disease progression. After 3 cycles, the response would be reported as CR equivalent as the patient had trilineage count recovery with full disappearance of the cytogenetic abnormity. As the baseline BM blast count was <5%, the patient is not evaluable for CR. |
| Case 7: disease relapse | A patient with HR-MDS is treated with azacitidine monotherapy and achieves a CR after cycle 4. He continues on azacitidine for another 3 cycles when he is noted to have a decrease in his Hb from 11.2 g/dL at best response to 9.5 × 109/L in the setting of an upper gastrointestinal tract bleed. After endoscopy, his Hb improves back to 11.5 g/dL. Per the IWG 2006 MDS criteria, such a transient decline in Hb would be classified as disease relapse. Per IWG 2023 MDS criteria, this would not be classified as disease relapse because of the transient nature of worsening anemia in the setting of a concurrent illness. |
| Case 8: time-to-event outcomes | A patient with HR-MDS with severe pancytopenia and 9% BM blasts is enrolled in a single-arm, phase 2 clinical trial, which investigates a novel combination of a HMA + an investigational agent. The trial uses EFS as the primary end point. After 3 mo of therapy, the patient continues to be deeply pancytopenic and a BM assessment shows 6% blasts. The investigator is deciding whether this situation constitutes failure of therapy as it is not addressed in the clinical trial protocol. EFS per the IWG 2006 criteria is defined as “failure or death from any cause” without providing an explicit definition of “failure”.16 Per IWG 2023 MDS criteria, an event would be defined as (1) PD; (2) failure to achieve CR (or CR equivalent), PR, CRL, CRh, or HI within 6 mo of study entry; (3) Relapse from CR (or CR equivalent), PR, CRL, CRh + HI; or (4) death from any cause. Per IWG 2023 criteria, this patient did not experience a “failure” event and is still within the 6-mo window during which HMA-based therapy can still lead to an objective response, and therefore, can continue on-trial therapy unless protocol explicitly recommends otherwise. |
| Case 9: SD | A patient with a baseline of 6% BM blasts, Hb 9.0 g/dL, platelets 55 × 109/L, and ANC 1.3 × 109/L notes subjective improvement in his quality of life with treatment despite no change in peripheral blood counts or BM blast counts. By IWG 2006 criteria, the patient is classified as SD. Per IWG 2023 MDS criteria, SD is not recognized as a formal response, and if SD is noted, it should not be included in the ORR. |
VAF, variant allele frequency.