Leukemia & MDS

Dr. Andre Schuh – Princess Margaret Cancer Centre

About Speaker

Dr. Andre Schuh – Princess Margaret Cancer Centre

Dr. Andre Schuh obtained his MD degree at the University of Toronto, Ontario, Canada, in 1983, and thereafter received subspecialty certification in Internal Medicine (1987) and Hematology (1988), followed by a four year Molecular Biology Fellowship.  Dr. Schuh has been a staff physician at the University Health Network/Princess Margaret Cancer Centre, Toronto, Ontario, since 1992, where he has long focused on acute leukemia and MDS. He was the head of the leukemia program at Princess Margaret from 2010-2014, and from 2012-2018, was Medical Director, Malignant Hematology.   His current interests include Acute Leukemia management and clinical trials (especially in the older patient), and the development of Canadian province- and country-wide leukemia management strategies.

AML Highlights from ASCO and EHA 2021

New and exciting results from landmark studies
Prognostic factors of overall (OS) and relapse-free survival (RFS) for patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy (IC): Multivariate analyses from the QUAZAR AML-001 trial of oral azacitidine (Oral-AZA)

Roboz et al.
ASCO 2021 Abstract 7014.
EHA 2021 Abstract EP428.

Results Highlights:

  • MV analyses were performed to identify BL characteristics independently predictive of OS/RFS in QUAZAR AML-001, and to assess Tx effects of Oral-AZA vs. PBO on survival when adjusted for BL factors
    • Age, sex, ECOG PS score, cytogenetic risk at diagnosis (Dx), prior MDS, geographic region, CR/CRi after induction at BL, MRD status, receipt of consolidation, number of consolidation cycles, platelet count, and ANC
  • While cytogenetic risk at Dx, MRD status, and age were independent predictors of survival, Tx with Oral-AZA reduced the risk of death by 30% and risk of relapse by 43% vs. placebo, independent of baseline factors

Key Takeaway:

This update supports the notion that this strategy can be used widely. CC-486 is approved, but not yet reimbursed in Canada.

Follow-up of patients with FLT3-mutated R/R AML in the phase 3 ADMIRAL trial.

Perl et al.
ASCO 2021 Abstract 7013.
EHA 2021 Abstract EP438.

Results Highlights:

  • Study assessed long-term survivors, transplant (HSCT) outcomes. and gilteritinib safety beyond 1 year (reanalysis after 2 years)
  • More patients in gilteritinib arm (n=64) underwent alloSCT, than in the SC arm (n=19)
  • 40/64 (62.5%) of gilteritinib patients resumed gilteritinib post alloSCT
  • A high proportion of long-term gilteritinib survivors underwent alloSCT followed by maintenance therapy and there was a very low post-alloSCT relapse rate may relate to maintenance therapy
  • no new safety signals

Key Takeaway:

gilteritinib is approved, but not yet reimbursed in Canada. These results reinforce its use in R/R FLT3-mutated AML, but also suggests that subsequent alloSCT and maintenance therapy are important.

New and exciting results from landmark studies
A phase Ib/II study of ivosidenib with venetoclax +/- azacitidine in IDH1-mutated myeloid malignancies.

Lachowiez et al.
ASCO 2021 Abstract 7012.
EHA 2021 Abstract S136.

Results Highlights:

  • Both VIALE-A and VIALE-C studies showed particular efficacy of venetoclax combinations in IDH-mutated patients; this study investigated whether ivosidenib + venetoclax combinations could be even more efficacious
  • 3 dose levels:
    • DL1: ivosidenib 500 mg daily (d15 onwards) + Venetoclax 400 mg daily (d1-14)
    • DL2: ivosidenib 500 mg daily (d15 onwards) + Venetoclax 800 mg daily (d1-14)
    • DL3: ivosidenib 500 mg daily (d15 onwards) + Venetoclax 400 mg daily (d1-14) + azacitidine 75mg/m2 d1-7 every 28 days
  • small numbers, and relatively short follow-up, but…
    • acceptable toxicity with no new safety signals
    • DL2/3 perform better than DL1
    • ORR 92%
    • CRc 84%
    • MRD -ve, 60%
    • durable
  • 1 year OS 68% ( DL1, 50%; DL2, 67%; DL3, 78%)

Key Takeaway:

This is likely the optimal combination of the future, but neither Ivosidenib or Venetoclax are currently available in Canada.

Effect of olutasidenib (FT-2102) on complete remissions in patients with relapsed/refractory (R/R) mIDH1 acute myeloid leukemia (AML): Results from a planned interim analysis of a phase 2 clinical trial.

De Botton et al.
ASCO 2021 Abstract 7006.
EHA 2021 Abstract S138

Results Highlights:

  • Of 153 patients enrolled (duration of therapy 5.5 m), the 123 patient ‘efficacy set’ (defined as patients receiving first dose ≥180 days pre data cut-off) was reported
  • CR/CRh was 33% (CR 30%)
  • median OS 10.5, with DOR and OS benefit not restricted to CR+CRh responders
  • median duration of CR/CRh not reached, with estimated 18 m OS ~87%
  • transfusion independence achieved in 100% of CR/CRh and in ~50% of lesser responders
  • olutasidenib was well tolerated with class-specific AEs (e.g. differentiation syndrome
  • 1 year OS 68% ( DL1, 50%; DL2, 67%; DL3, 78%)

Key Takeaway:

Olutasidenib appears to be efficacious and well-tolerated. It is not likely this will become available in Canada for quite some time.

Phase 2 results of the ZUMA-3 study evaluating KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult patients (pts) with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).

Shah et al.
ASCO 2021 Abstract 7002.
EHA 2021 Abstract S117.

Results Highlights:

  • CR (56%) + CRi (15%), 71%; with prior blinatumomab, 60%
  • in all infused patients:
    • overall median RFS, 11.6 m (2.7-15.5)
    • overall median OS, 18.2 m (15.9 – NR)
  • in responders:
    • median RFS, 14.2 m
    • median OS, NR
    • MRD response 97%
    • 18% proceeded to alloSCT
  • Toxicities:
    • Grade ≥3 AEs, 95%
    • Grade ≥3 CRS, 24%; onset after 5d with duration 7.5d
    • Grade ≥3 neurological, 25%; onset after 9d with duration 7d
    • Grade 5 AE, 2

Key Takeaway:

KTE-X19 demonstrated amazing data in adults (for whom a commercial product is available only up to age 25). Availability of this agent in Canada is highly anticipated.

Thank you to our CARE™ at ASCO/EHA Sponsors