MYELODYSPLASTIC SYNDROME

Update
17 Abstracts and Two Lectures

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Most repeated words in order of frequency…

• Azacitidine

• Venetoclax

• Combination Therapy

• Gene Based Prognostication models

• Not heard - Decitabine

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11
Treatment Algorithm Low Risk MDS: Today
New Agents to Target Transfusion Dependence in Lower Risk MDS
Imetelstat is a first-in-class telomerase inhibitor that targets cells
with short telomeres and active telomerase, characteristics
observed in MDS pts across all disease stages.
Slide 11
Slide 12
• Among 38 pts with median follow-up of 24 months, 8-week, 24-week and 1-

year TI rates were 42%, 32% and 29%, respectively

• Median TI duration was 20 months and the longest TI was 2.7 years

• Reduction of variant allele frequency of mutations by imetelstat treatment was

observed in some pts and correlated with clinical benefits 

Higher Risk Disease: improving response and duration is an unmet medical need
Predictors of Hypomethylating Agent Discontinuation Among Patients With Higher-Risk Myelodysplastic SYNDROMES
 Venetoclax + Azacitidine vs Azacitidine
Monotherapy in Chemotherapy-Ineligible Patients
With tAML or AML From Antecedent MDS or CMML

Pullarkat. ASCO 2021. Abs 7011.

 VEN + AZA in Secondary AML: Response
Rates, DoR, OS
tAML Antecedent MDS/CMML
Efficacy Outcome VEN + AZA (n VEN + AZA (n
AZA (n = 9) AZA (n = 26)
= 31) = 59)
Response, n (%)
 CR + CRi 19 (61.3) 1 (11.1) 39 (66.1) 7 (26.9)
 CR + CRh 18 (58.1) 2 (22.2) 36 (61.0) 5 (19.2)

Median DoR, mo
(95% CI) 17.3 (9.6-NR)
NR (17.8-NR) 8.5 5.8 (1.1-NR)
 CR + CRi NR (17.8-NR) 4.6 (0.5-NR)
17.4 (10.6-
15.6 (1.1-NR)
 CR + CRh NR)
Median OS, mo 11.1 (0.6- 15.9 (11.5- 10.1 (4.7-
16.4 (4.1-NR)
(95% CI) 17.5) NR) 14.5)
 HR (95% CI) 0.64 (0.27-1.53); P = .31 0.57 (0.33-1.00); P = .05

Pullarkat. ASCO 2021. Abstr 7011.

AZA + Venetoclax

Content of this presentation is the property of the author, licensed by ASCO. Permission required for reuse.
Comparison of Dose Modification Strategies to Address Expected Hematologic Toxicities in Treatment-naïve Higher-Risk MDS Patients Treated with
Venetoclax + Azacitidine
Dose Modifications per Protocol
Slide 4
 • No obvious hematologic differences
were observed when reducing Aza
before Ven (SE2) in MDS compared
to investigator’s choice (SE1).
Conclusion • Both approaches had a similar
acceptable safety profile without
compromising efficacy for pts with
HR-MDS
 Outcomes with Venetoclax in myelodysplastic syndromes

Complete response
8 studies (1
(CR) with or without Stable disease (SD)
prospective, 3
hematological recovery was seen in 18%
retrospective, 2 ex-vivo,
(CRi) was reported in patients
2 clinical trials)
45% of patients

Hematopoietic stem cell

Overall response rate transplant (HCT) was
(ORR) was 51% performed in 22%
patients

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 Phase II Study of IDH2 Inhibitor
Enasidenib in Patients With High-Risk
IDH2-Mutated MDS

Dr Sangeetha Venogopal
 Enasidenib in High-Risk IDH2-Mutated
MDS: Study Design
 Multicenter, open-label phase II trial (N = 46)
AZA 75 mg/m2/day IV or SC on Days
Arm A: patients with
higher-risk (IPSS-R 1-7 in
risk >3 or HMR) each 28-day cycle + ENA 100 mg PO
MDS/CMML or LB daily on Days 1-14 in each 28-day
AML; naive to HMA cycle
(n = 25)
Arm B: patients with ENA 100 mg PO daily continuously;
R/R MDS after HMA
therapy 28-day cycle
(n = 21)

 Primary endpoint: ORR (CR, mCR, PR, and HI)

 Additional endpoints: safety and survival outcomes

Venugopal. ASCO 2021. Abstr 7010.

 Enasidenib in High-Risk IDH2-Mutated
MDS: Investigator Conclusions
 Promising efficacy of enasidenib in high-risk IDH2-mutated MDS
‒ ORR of 84% in combination with AZA (HMA-naive patients)
‒ ORR of 43% as single agent (R/R after HMA)
 Median OS, mo (median follow-up: 12.6 mo):
‒ AZA + ENA: 32.2 mo
‒ ENA: 21.3 mo
 Enasidenib well-tolerated in patients with MDS
‒ Differentiation syndrome 17%, manageable

Venugopal. ASCO 2021. Abstr 7010.

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AZA + Pevonedistat
AZA + Magrolimab
 • Treatment options are limited for
patients with lower-risk
myelodysplastic syndromes (LR-
MDS).

• This phase III, placebo-controlled

Background trial evaluated CC-486 (oral
azacitidine), a hypomethylating
agent, in patients with International
Prognostic Scoring System LR-MDS
and RBC transfusion–dependent
anemia and thrombocytopenia
 • Patients were randomly assigned 1:1
to CC-486 300-mg or placebo for 21
days/28-day cycle.

METHODS • The primary end point was RBC

transfusion independence (TI)
 • CC-486 significantly improved RBC-TI
rate and induced durable bilineage
CONCLUSION improvements in patients with LR-
MDS and high-risk disease features.
Slide 18