View Abstract - Chemotherapy Foundation Symposium

ANAPLASTIC LARGE CELL LYMPHOMA
AND MABS AND TKI'S IN THE
TREATMENT OF LYMPHOMA
Eric Lowe, MD1
Children’s Hospital of The King’s
Daughters, Norfolk, VA
1
Despite numerous treatment strategies
over the last 20 years failure rates remain
25-30% for pediatric anaplastic large cell
lymphoma (ALCL) (1-8). Two novel agents
have demonstrated high response rates as
single agents in ALCL. Brentuximab
vedotin (previously known as SGN35;
currently marketed under the brand name
Adcetris) is an antibody-drug conjugate
containing an anti-CD30 monoclonal
antibody linked to a tubulin inhibitor
(monomethylauristatin E). After binding
CD30, a transmembrane receptor
expressed on all ALCLs, brentuximab
vedotin is internalized and the drug is
released into the cytoplasm where it
causes cell cycle arrest and apoptosis.
Tubulin inhibitors are active agents in
ALCL as evidenced by responses using
vincristine and vinblastine. The response
rate of brentuximab vedotin in patients with
relapsed/refractory ALCL is impressive and
the FDA has approved brentuximab
vedotin for the treatment of patients with
ALCL that have failed one line of therapy
(9-13). Crizotinib is an orally bioavailable
small molecule inhibitor of receptor tyrosine
kinases including anaplastic large cell
lymphoma kinase (ALK). ALK plays a
central role in the pathogenesis of ALCL
due to a chromosomal translocation that
results in expression of an oncogenic
kinase fusion protein. Crizotinib inhibits
ALK phosphorylation resulting in antitumor
activity. Crizotinib has shown impressive
response rates in patients with
refractory/relapsed ALK positive ALCL (1416).
Given the impressive activity of both
brentuximab vedotin and crizotinib, the
next challenge for investigators is to design
treatment strategies which optimize
treatment for patients with recurrent and
newly diagnosed ALCL.
References
1. Seidemann K, Tiemann M, Schrappe
M, et al: Short-pulse B-non-Hodgkin
lymphoma-type chemotherapy is
efficacious treatment for pediatric
anaplastic large cell lymphoma: a report
of the Berlin-Frankfurt-Munster Group
Trial NHL-BFM 90. Blood 97:3699-706,
2001
2. Brugieres L, Deley MC, Pacquement
H, et al: CD30(+) anaplastic large-cell
lymphoma in children: analysis of 82
patients enrolled in two consecutive
studies of the French Society of
Pediatric Oncology. Blood 92:3591-8,
1998
3. Brugieres L, Le Deley MC, Rosolen
A, et al: Impact of the methotrexate
administration dose on the need for
intrathecal treatment in children and
adolescents with anaplastic large-cell
lymphoma: results of a randomized trial
of the EICNHL Group. J Clin Oncol
27:897-903, 2009
4. Laver JH, Kraveka JM, Hutchison
RE, et al: Advanced-stage large-cell
lymphoma in children and adolescents:
results of a randomized trial
incorporating intermediate-dose
methotrexate and high-dose cytarabine
in the maintenance phase of the APO
regimen: a Pediatric Oncology Group
phase III trial. J Clin Oncol 23:541-7,
2005
5. Lowe EJ, Sposto R, Perkins SL, et al:
Intensive chemotherapy for systemic
anaplastic large cell lymphoma in
children and adolescents: final results of
Children's Cancer Group Study 5941.
Pediatr Blood Cancer 52:335-9, 2009
6. Rosolen A, Pillon M, Garaventa A, et
al: Anaplastic large cell lymphoma
treated with a leukemia-like therapy:
report of the Italian Association of
Pediatric Hematology and Oncology
(AIEOP) LNH-92 protocol. Cancer
104:2133-40, 2005
7. Williams DM, Hobson R, Imeson J, et
al: Anaplastic large cell lymphoma in
childhood: analysis of 72 patients
treated on The United Kingdom
Children's Cancer Study Group
chemotherapy regimens. Br J Haematol
117:812-20, 2002
8. Le Deley MC, Rosolen A, Williams
DM, et al: Vinblastine in children and
adolescents with high-risk anaplastic
large-cell lymphoma: results of the
randomized ALCL99-vinblastine trial. J
Clin Oncol 28:3987-93, 2010
9. Fanale M, Bartlett NL, Forero-Torres
A, et al: The Antibody-Drug Conjugate
Brentuximab Vedotin (SGN-35) Induced
Multiple Objective Responses in
Patients with Relapsed or Refractory
CD30-Positive Lymphomas in a Phase 1
Weekly Dosing Study. ASH Annual
Meeting Abstracts 114:2731-, 2009
10. Younes A, Bartlett NL, Leonard JP, et
al: Brentuximab vedotin (SGN-35) for
relapsed CD30-positive lymphomas. N
Engl J Med 363:1812-21, 2010
11. Younes A, Forero-Torres A, Bartlett
NL, et al: Multiple Complete Responses
in a Phase 1 Dose-Escalation Study of
the Antibody-Drug Conjugate SGN-35 in
Patients with Relapsed or Refractory
CD30-Positive Lymphomas. ASH
Annual Meeting Abstracts 112:1006-,
2008
12. Advani RH, Shustov AR, Brice P, et
al: Brentuximab Vedotin (SGN-35) in
Patients with Relapsed or Refractory
Systemic Anaplastic Large Cell
Lymphoma: A Phase 2 Study Update.
ASH Annual Meeting Abstracts 118:443, 2011
13. Chen R, Gopal AK, Smith SE, et al:
Results of a Pivotal Phase 2 Study of
Brentuximab Vedotin (SGN-35) in
Patients with Relapsed or Refractory
Hodgkin Lymphoma. ASH Annual
Meeting Abstracts 116:283-, 2010
14. Chiarle R, Voena C, Ambrogio C, et
al: The anaplastic lymphoma kinase in
the pathogenesis of cancer. Nat Rev
Cancer 8:11-23, 2008
15. Gambacorti-Passerini C, Messa C,
Pogliani EM: Crizotinib in anaplastic
large-cell lymphoma. N Engl J Med
364:775-6, 2011
16. Mosse YP, Balis FM, Lim MS, et al:
Efficacy of crizotinib in children with
relapsed/refractory ALK-driven tumors
including anaplastic large cell lymphoma
and neuroblastoma: A Children's
Oncology Group phase I consortium
study. J Clin Oncol 30, 2012

Download Report