Acute Lymphoblastic Lymphoma: Treatment Update. Nina Shah

1. Acute lymphoblastic lymphoma:
Updates from ASCO and EHA
Nina Shah, MD
Department of Stem Cell
Transplantation and Cellular Therapy
M.D. Anderson Cancer Center
Houston, TX

2. Treatment paradigm
Induction Consolidation Maintenance
Relapse
HSCT
MRD
monitoring

3. Long-term data with HVCAD1
• Ph+ adults
• HVCAD + dasatinib induction (included
MTX/Ara-C): total 8 cycles
• Dasatinib/vincristine/prednisone x 2 years
• Indefinite dasatinib
• Median f/u 67 months:
– 46% alive
– 43% in CR
1. Ravandi et al, Cancer 2015

4. Upfront treatment of ALL
• Kim et al, EHA abs #p167
• Phase II trial: Rituximab +
vincristine/prednisolone/daunorubicin/L-
asparaginase consolidation chemo-R
maintenance
• N=36
• 1-year and 21 –month RFS were 71.5% and
49.1%,

5. Treatment of MRD in ALL
• Blinatumomab: “BiTE” technology directed at
CD19 and CD3 to bring target cells close to
effector cells
• Original phase 2 data showed 43% CR in R/R
pts1
• Phase 2 results from ASH 2014 (Goekbuget et
al) for pts with MRD positivity
• MRD response rate of 80%
1. Topp et al, Lancet Oncol, 2015

6. Upfront treatment of ALL- older pts
• Pfeifer et al, EHA abs #S113
• Nilotinib + chemotherapy for pts >55 years
• Ph+ ALL
• Induction: nilotinib + vincristine and Dex, weekly x 4
weeks
• Consolidation: nilotinib, methotrexate (MTX) and
asparaginase for cycles 1, 3 and 5 and cytarabine for
cycles 2, 4 and 6.
• Maintenance: nilotinib, 6-MP, MTX and Dex/VCR
• CHR=87%
• MMR 46%
• Well-tolerated
An option for our older Ph+ ALL patients

7. Upfront treatment of ALL- older pts
• Papayannidis, EHA abs #P163
• Sequential nilotinib (400 BID) with imatinib
(300 BID) alternating for 6 weeks for 24
weeks/ indefinitely
• OS at 1 year is 82%, and 64% at 2 years
• Median time to relapse of 9.2 months

8. Upfront treatment of ALL-older pts
• Jabbour, EHA Abs #S114
• Inotuzumab-ozogamicin + mini Hyper-CVD
• Pts >60 years
• N= 33
• CR/CRp = 97%
• 2-year PFS: 85%
• 2- year OS: 70%

9. T-ALL
• Lepretre et al, ASH 2014
• Pediatric-like regimen
• corticosteroid prephase 5-drug induction with
sequential cyclophosphamide high dose
consolidationlate intensification
• CNS prophylaxis with IT injections and cranial
irradiation,
• 2-year maintenance.
• 5 years DFS, EFS and OS: 71%, 61% and 66%,

10. RELAPSED ALL

11. Relapsed ALL
• Bertrand et al, ASCO abs #7004
• Randomized phase II study of ERY001 (erythrocyte
encapsulated l-asparaginase) and native l-
asparaginase (L-ASP) with COOPRALL regimen
• ERY001 improves PKs, tolerability and maintains
circulating asparaginase
• ERY001 significantly reduced the incidence of ASPA
hypersensitivity (0% vs 43%; p < 0.001)
• Lengthened time of ASPA activity (21 vs 9 days)
• The CR rate: ERY001 (65%) vs L-ASP (39%) p = 0.026
• 12 mo EFS rate was 65% vs 49%

12. Relapsed ALL- CD19 CAR T cells
• Park et al, ASCO abs #7010
• 19-28z CAR T cells (anti-CD19 scFv linked to CD28
and CD3ζ signaling domain)
• Long-term outcome of phase I trial
• N= 33, 32 evaluable
• overall CR rate of 91% (29/32)
• MRD negative CR rate was 82%
• 6-month overall survival (OS) rate of all patients
was 58%, 70% for those achieving CR
• Cytokine release syndrome (CRS) in 7, managed
with anti IL-6 or steroids

13. Relapsed ALL- CD19 CAR T cells with
CD8 and CD4-selection
• Turtle, et al ASH 2014
• Selection of CD4 and CD8 cells in separate
cultures
• CD3/CD28 stimulation
• Transduction with anti-CD19 scFv linked to 4-
1BB and CD3 zeta signaling domains
• Product = 1:1 ratio of CD4 :CD8 CAR T cells
• CR in 5/7 ALL pts (early data)

14. CAR-T cells upfront during HSCT
• Kebriaei et al, EHA abs #S802
• 2nd generation CD19-specific CAR (CD19RCD28)
that activates via CD3z/CD28
• From donor derived T cells for patients with
advanced CD19+lymphoid malignancies (ALL =13,
16 total)
• Infused at median 64 days after allo-transplant
• No toxicities
• 50% patients (n=8) alive and in CR at median 7.2
• months (range 2.1-21.3 months) following HSCT

15. Relapsed ALL- Blinatumomab
• Topp et al, ASCO abs #7051
• Bispecific T-cell engager antibody construct to link
cytotoxic T cells (CD3) and CD19-positive B cells
• Re-exposure to blinatumomab after CD19-positive
relapse: Experience from three trials (n=11)

16. Treatment of ALL-older pts with
relapsed disease
• Kantarjian1 et al, EHA Abs #S115
• Blinatumomab 4 weeks on, 1 week off, up to 5
cycles
• N=36
• CR/CRh = 56% with 60% of these MRD negative
• RFS 7.4 mo
• Cyotpenias, 1 pt with cytokine release
syndrome

17. Relapsed ALL- trials in progress
• DeAngelo et al, EHA abs #LB2073
• Inotuzumab ozogamicin (InO) vs SOC (FLAG or
mitoxantrone-Ara C or HiDAC) in adults with
relapsed/refractory ALL

18. Conclusions
• Paradigm for ALL still rests on long sequence of
induction, consolidation and maintenance
chemotherapy
• Addition of TKIs for Ph+
• Efforts to eradiate MRD (Blinatumomab)
• More options for our older pts
• Relapsed ALL is still a challenge:
– Inotuzumab
– HSCT
– CAR-T cell therapy

19. Thank you!