GMALL 08/2013: First Results From the

Risk-Adapted, MRD-Stratified Trial in

Adults With Newly Diagnosed ALL/LBL
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of the 2021 ASH Annual Meeting, December 11-14, 2021
Atlanta, Georgia
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 GMALL 08/2013: Background
 Intensive chemotherapy is essential for attaining cure in adult ALL1,2
‒ Toxicities, development of resistance, and R/R disease remain a limitation
in ALL
‒ There is a need for optimization of standard chemotherapy and the
development of new targeted agents that can be used in early-stage ALL 2
 In ALL, the use of pediatric regimens optimized for use in adolescents
and young adults has improved survival1-3
 The current trial is evaluating an individualized, targeted, and
intensified treatment in adults with newly diagnosed ALL or LBL4

1. Gökbuget. Drugs Aging. 2018;35:11. 2. Gökbuget. Hematology Am Soc Hematol Educ Program. 2016;573.
3. Stock. Blood. 2019:1548. 4. Goekbuget. ASH 2021. Abstr 362. Slide credit: clinicaloptions.com
 GMALL 08/2013: Study Design
 Phase III/IV trial of nelarabine chemotherapy in patients with ALL
Risk Stratification
 Pro‒B-ALL and/or KMT2A rearrangement
 Early/mature T-ALL
 B-precursor: WBC >30,000 cells/mm3
 No CR after induction I plus molecular failure after consolidation I

Patients aged 18-55 yr with Treatment Protocol: Randomization I Randomization II

newly diagnosed ALL or LBL;  BFM-based pediatric regimen
cytostatic pretreatment*;  Dexamethasone during SCT vs standard Maintenance
induction/consolidation CNS irradiation vs therapy in HR up to
severe uncontrolled i.th. prophylaxis in
complications of ALL or  9x pegylated asparaginase patients with molCR 2.5 yr
(2000-1000-500 U/m2) B-ALL/LBL after induction
secondary diseases
 7x HDMTX (1.5 g/m2)
(planned N = 950)
 Reinduction
*With exception of prephase  Risk-adapted SCT indication EoT LBL
application a cytostatic drug,
steroids, ≤7 days or up to 3 days.
HDMTX B-Lin HDMTX B-Lin HDMTX
Induction Consolidation I ASP-MP Reinduction HDAC/CP ASP-MP HDAC/CP ASP-MP
Wk 1 Wk 52
T-Lin: Nela/CP T-Lin: Nela/CP
 Primary endpoint: EFS (time frame: 3.5 yr)  Secondary endpoint: time until treatment
consolidation and DFS (time frame: 1 yr)
Goekbuget. ASH 2021. Abstr 362. NCT02881086. Slide credit: clinicaloptions.com
 GMALL 08/2013: Baseline Characteristics
Characteristic Patients With ALL Patients With LBL
(n = 638) (n = 67)
Median age, yr 35 32
Age category, %
 18-35 yr 51 55
 36-45 yr 22 15
 46-55 yr 27 30
Male, % 60 72
Subtype, %
 B-precursor, Ph negative 55 12
 B-precursor, Ph positive 20 --
 T-cell lineage 25 88
BMI ≥30 kg/m2, % 20 24
Steatosis hepatis, % 28 23

Goekbuget. ASH 2021. Abstr 362. Slide credit: clinicaloptions.com

 GMALL 08/2013: Response
Following First Consolidation
Characteristic All Patients B-ALL B-ALL T-ALL B/T B/T
Ph- Ph+ SR HR
Evaluable for hematologic response, n 599 326 122 151 261 217
 Hematologic CR, % 93 94 95 89 96 88
 Early death, % 4 5 3 5 3 7
 Failure/PR, % 3 1 2 7 1 4
Evaluable for molecular response, n 542 306 116 120 248 178

 Molecular response, % 75 76 58 87 86 70
 Molecular CR, % 61 65 41 67 74 54
 Molecular failure, % 19 18 28 11 10 25
 MRD low positive, % 14 11 17 20 12 16
 Not evaluable, % 6 6 13 3 4 5

Goekbuget. ASH 2021. Abstr 362. Slide credit: clinicaloptions.com

 GMALL 08/2013: Use of Peg-Asparaginase
 Peg-asparaginase dosing:
‒ Ph negative: 2000 U/m2 Day 20 induction I and Day 44 induction II
‒ Ph positive: 2000 U/m2 Day 20 and Day 34 of induction
 Dose reduction to 500 U/m2 for first dose if:
‒ BMI >30 kg/m2, steatosis hepatis, preexisting liver toxicities, comorbidities
‒ Recommendation: Withhold second dose if relevant asparaginase-
associated toxicities occur; adapt dose to toxicity and activity duration

Goekbuget. ASH 2021. Abstr 362. Slide credit: clinicaloptions.com

 GMALL 08/2013: Asparaginase Therapy
First Dose Second Dose Dose and
Asparaginase Bilirubin GOT/GPT
Hepatotoxicity, %
Dosing, % Ph- Ph+ Ph- Ph+
Ph-
2000 U/m2 66 61 43 41  2000 U/m2 24 25
 500 U/m2 18 29
500 U/m2 24 21 21 24
Ph+
Other doses 9 13 22 22  2000 U/m2 5 40
No ASP 1 6 13 13  500 U/m2 3 24

Goekbuget. ASH 2021. Abstr 362. Slide credit: clinicaloptions.com

 GMALL 08/2013: Efficacy After Targeted Consolidation II
 63 patients with SR/HR had molecular failure and were candidates for targeted
consolidation II followed by SCT; 51 of 56 patients who received targeted therapy
were evaluable
‒ B-precursor: blinatumomab (n = 40), 55% molecular response rate
‒ T-ALL: nelarabine (n = 11), 18% molecular response rate
 Ph-positive patients with molecular failure (>10-3) were candidates for alternative
TKI followed by SCT (amendment I) (n = 32)
 3-yr OS in patients with ALL with molecular failure
‒ Ph negative: 75% (n = 63)
‒ Ph positive: 79% (n = 32)

Goekbuget. ASH 2021. Abstr 362. Slide credit: clinicaloptions.com

 GMALL 08/2013: OS
3-year OS rate, % 3-year OS rate, %
All patients (N = 705) 76 By age
ALL (n = 638) 76  18-25 yr (n = 204) 87
 26-35 yr (n = 160) 74
LBL (n = 67) 82  36-45 yr (n = 150) 69
 46-55 yr (n = 191) 73
Median follow-up: 23 mo.
By disease subtype or treatment
 B-precursor Ph- (n = 350) 77
 B-precursor Ph+ (n = 128) 74
 T-ALL (n = 160) 74
 Standard risk (n = 72) 86
 Underwent SCT (n = 228) 76

Goekbuget. ASH 2021. Abstr 362. Slide credit: clinicaloptions.com

 GMALL 08/2013: Investigators’ Conclusions
 Preliminary results were promising in this large, unselected cohort of patients
‒ Data suggest a pediatric-based regimen is feasible and effective in patients up to age 55 yr
‒ This large, multicenter study supports the notion that intensive individualized therapy is feasible
 MRD-based targeted therapy was administered in a high percentage of patients
 Lower than expected molecular response rates to blinatumomab or nelarabine were
observed in patients with molecular failure
‒ Blinatumomab: 55%; nelarabine: 18%
 OS of patients with molecular failure were promising with the combination of targeted
therapy and SCT
 According to investigators, SCT remains an important component of therapy for adults with
newly diagnosed ALL or LBL, although the overall SCT rate was lower than that observed in
prior GMALL trials
Goekbuget. ASH 2021. Abstr 362. Slide credit: clinicaloptions.com
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