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Challenging Cases in
Non-Hodgkin Lymphoma
Oncologist and Nurse Investigators
Consult on Actual Patients from the
Practices of the Invited Faculty
Thursday, May 1, 2014
12:00 PM – 1:30 PM
Faculty
Lauren C Pinter-Brown, MD
Mitchell R Smith, MD, PhD
Amy Goodrich, CRNP-AC
Barbara Barnes Rogers, CRNP,
MN, AOCN, ANP-BC
Moderator
Neil Love, MD
Oncology 6-Part Case Series: Key Themes
• Mechanisms of action of novel agents and tissue
assays to predict response
• Side effects and toxicities of novel agents; dose
adjustments
• Assessment and management of adherence
• Specific goals of therapy and likely outcomes;
sequencing of agents in advanced disease
• Local and systemic complications of cancer: Fatigue,
pain, CNS involvement
• Care of older, frail patients and those with comorbidities
Oncology 6-Part Case Series: Key Themes
• Clinical trials as a means to access new treatments earlier
• Management of anxiety and depression
• Key determinants of patient satisfaction: What do people
with cancer want and need?
• Quality, value and cost: Investing resources optimally
• End-of-life care and planning
• Impact of the cancer experience on family and loved
ones, including minor children
• Impact of the oncology experience on oncology health
professionals
Agenda
A Patient with Mantle-Cell Lymphoma (MCL) Who
Received Multiple Lines of Therapy
• 52 yo man with relapsed MCL whose wife is dying of
metastatic endometrial cancer (Ms Goodrich)
A Patient with Chronic Lymphocytic Leukemia (CLL)
in Remission
• 69 yo man with CLL currently in remission
(Ms Rogers)
Agenda
Two Patients with Follicular Lymphoma (FL) Who
Received Rituximab/Chemotherapy Followed by
Rituximab Maintenance
• 48 yo man with FL and multiple health problems related
to chronic obesity (Ms Goodrich)
• 56 yo man with FL and comorbid community-acquired
clostridium difficile infection (Ms Rogers)
A Patient with Angioimmunoblastic T-Cell Lymphoma
(TCL) and a Patient with ALK-Negative Anaplastic Large
Cell Lymphoma (ALCL)
• 53 yo man with rapidly progressive disease (Ms Goodrich)
• 65 yo man who delayed allogeneic STC and had rapid
disease progression (Ms Rogers)
Case 1 (from the practice of Ms Goodrich)
• A 52-year-old man was diagnosed with Stage IVA MCL
in 2009
• He responded to R-CHOP and was considered for
autologous stem cell transplant (SCT), but his cardiac
ejection fraction was 41%
• Eighteen months later, disease progression occurred
• He received bendamustine/rituximab (BR) x 2 cycles,
then R-ICE x 3 followed by allogeneic SCT
• He then developed multiple subcutaneous relapses and
underwent treatment with rituximab/radiation therapy
and bortezomib/radiation therapy
• Most recently, treatment with ibrutinib has been initiated
• His wife, who sees the same medical oncologist, is
dying of metastatic endometrial cancer
Discussion Point
Treatment of newly diagnosed MCL in
younger and older patients; role of
rituximab maintenance
Common Induction Regimens for MCL
• Aggressive Therapy
– CALGB regimen
– R-hyper-CVAD
– NORDIC regimen
– R-CHOP/R-DHAP
• Less Aggressive
Therapy
– Bendamustine/R
– R-CHOP
– Modified
R-hyper-CVAD
– Cladribine/R
European MCL Maintenance Study
R maintenance
375 mg/m2 q2m
R-CHOP
Eligibility
• >60 yo with Stage
II-IV MCL
• Not eligible for HDT
•
•
R
CR/CRu
or PR
R-FC
R
IFN maintenance
Maintenance R reduced the risk of progression or death by 45%
In patients responding to R-CHOP, maintenance R improved overall survival
Kluin-Nelemans HC et al. N Engl J Med 2012;367:520-31.
Discussion Point
Major questions being tested in
ongoing up-front trials; bortezomib as
part of induction; lenalidomide as
maintenance
Mechanisms of Action of Proteasome Inhibitors
Adapted from Paramore A, Frantz S. Nat Rev Drug Discov 2003;2(8):611-2.
Bortezomib
• FDA approved for R/R MCL
– 1.3 mg/m2 IV days 1, 4, 8, 11 q 21 days
– SQ dosing now an option
• Phase II PINNACLE trial (n = 155)
– ORR: 32%
– mDOR: 9.2 months
– mTTP: 6.7 months
– Peripheral neuropathy main toxicity
- 55% (any grade), 13% (Grade ≥3)
Fisher RI et al. JCO 2006;24(30):4867-74; Goy A et al. Ann Oncol 2009;20(3):520-5.
Lenalidomide:
Mechanism of action in lymphoma
T-Cell Effects
Immune synapse
formation
T-cell activation
and proliferation
CD8+ T effector
cell activity
B-CLL Cell Effects
APC function
CXCR4 expression
NK-Cell Effects
Immune synapse
formation
ADCC
Direct NK-mediated
killing
Microenvironmental Effects
FGF2
Altered cytokine levels
IgG production
Lenalidomide
• FDA approved for R/R MCL after 2 prior therapies, one
including bortezomib
– 25 mg po days 1-21 q 28 days
• Phase II EMERGE study (n = 134)
– ORR: 28%
– mDOR: 16.6 months
– mPFS: 4.0 months
– Major toxicities
- Grade 3/4: Neutropenia (43%); thrombocytopenia
(27%)
- Any grade: Fatigue (34%), diarrhea (31%), nausea
(30%)
Goy A et al. JCO 2013;31(29):3688-95.
ECOG-E1411 Phase II Study in Older
Patients with Untreated MCL
Target Accrual: 332 (Active, recruiting)
BR  R
Eligibility
• Previously
untreated MCL
• Age ≥60
• No CNS mets
R
BVR  R
BR  LR
Primary Endpoint: PFS at 2 yrs
B = bendamustine
V = bortezomib
R = rituximab
L = lenalidomide
www.clinicaltrials.gov, April 2014
BVR  LR
ClinicalTrials.gov Identifier: NCT01415752
Antigen-Dependent B-Cell Receptor Signaling and
Its Targeting by Small-Molecule Inhibitors
Adapted from Wiestner A. J Clin Oncol 2013;31:128-30.
Ibrutinib
• FDA approved for R/R MCL - Nov 2013
– 560 mg po daily
• Phase II trial (n = 111)
– ORR: 68%
– mDOR: 17.5 months
– mPFS: 13.9 months
– Major toxicities
– Grade 3-4: Neutropenia 16%,
thrombocytopenia 11%
– Any grade: Diarrhea 50%, fatigue 41%,
edema 28%
Wang ML et al. NEJM 2013;369(6):507-16.
Case 2 (from the practice of Ms Rogers)
• A 69-year-old retired man diagnosed with CLL in 2006
was observed without medical treatment for several
years but used Chinese herbal products for his disease
• In 2009 he developed splenomegaly with abdominal
discomfort and received single-agent bendamustine
70 mg/m2
• He developed a rash that was difficult to treat but
resolved when he discontinued use of the herbal
products
• In 2012 he experienced disease recurrence for which
he received bendamustine 90 mg/m2 and rituximab
• Currently his disease is in remission and he is being
observed
Discussion Point
Risks, benefits and available data with
common induction regimens for
younger and older patients requiring
treatment
Common Induction Regimens in CLL
Regimen
ORR
Median PFS
FCR
90%
52 mo
84%
42 mo
88%
34 mo
(fludarabine, cyclophosphamide, rituximab)
FR
(fludarabine, rituximab)
BR
(bendamustine, rituximab)
Wierda WG. J Clin Oncol 2012;30(26):3162-4.
Toxicity Issues
Common Concerns
• Prolonged myelosuppression
• Treatment-related myeloid neoplasia
Fludarabine
• F(C)R difficult to tolerate in older patients
• Immunosuppression
• Renal excretion
• Exacerbation of AIHA
Bendamustine
• Rash
• Hypersensitivity
German CLL10 Phase III Study Design
Target Accrual: 564 (Active, not recruiting)
FCR
Eligibility
• Untreated B-cell CLL
• Binet Stage C
• Binet Stage A/B with B
symptoms or constitutional
symptoms
R
BR
Median follow-up: 27.9 months
• Complete response rate:
• 2-year progression-free survival:
• 2-year overall survival:
www.clinicaltrials.gov, April 2014
Eichhorst B et al. Proc ASH 2013;Abstract 526.
FCR
47.4%
85%
94.2%
BR
38.1%
78.2%
95.8%
ClinicalTrials.gov Identifier: NCT00769522
Discussion Point
Incidence of various cytogenetic
abnormalities (13q and 17p deletions,
et cetera) and their impact on
therapeutic decision-making
Discussion Point
Mechanisms of action of Type I and II
anti-CD20 monoclonal antibodies;
trial of obinutuzumab/chlorambucil
Mechanisms of Action of Anti-CD20 Antibodies
Complement-mediated lysis
C1q binding
MAC
ADCC
Cell
lysis
FCgRIIIa
Effector
cell
B-cell NHL
(tumor cell)
CD20
antigen
Direct effects
Antibody binding induces
antiproliferative signaling, apoptosis
and cell-growth inhibition
Adapted from Maloney DG. N Engl J Med 2012;366:2008-16.
CD20
Cell
membrane
Rituximab and
obinutuzumab
binding site
Comparison of cell death induced by
obinutuzumab and rituximab
Type II
anti-CD20
antibody1
Enhanced
DCD vs
rituximab2
ADCC = antibody-dependent cell-mediated cytotoxicity;
DCD = direct cell death.
1. Niederfellner G et al. Blood 2011;118:358-67.
2. Alduaij W et al. Blood 2011;117:4519-29.
3. Mössner E et al. Blood 2010;115:4393-02.
4. Herter S et al. Poster presentation at ASH 2010 (Abstract 3925).
Glycoengineered
Fc region3
Up to 100-fold
increase in
ADCC vs
rituximab3,4
FDA Approves the Use of Obinutuzumab in
Combination with Chlorambucil for CLL
“On November 1, 2013, the US Food and Drug
Administration (FDA) approved obinutuzumab (GA101)
for use in combination with chlorambucil for the
treatment of patients with previously untreated CLL,
based on demonstration of an improvement in PFS in a
randomized open-label multicenter trial that compared
obinutuzumab in combination with chlorambucil (GClb)
with chlorambucil (Clb) alone in patients with previously
untreated CD20-positive CLL.”
http://www.cancer.gov/cancertopics/druginfo/fda-obinutuzumab
German CLL 11 Phase III Study
Target Accrual: 786 (Active, not recruiting)
Chlorambucil +
Obinutuzumab
Eligibility
Previously untreated
CD20+ B-cell CLL
Primary Endpoint: PFS
R
Chlorambucil +
Rituximab
Chlorambucil
Final Stage 2 Results:
Median PFS: 26.7 mo (chlorambucil/obinutuzumab)
vs
15.2 mo (chlorambucil/R)
www.clinicaltrials.gov, April 2014 ClinicalTrials.gov Identifier: NCT01010061
Goede V et al. New Eng J Med 2014;370(12):1101-10
CLL 11: Obinutuzumab plus Chlorambucil
versus Rituximab plus Chlorambucil in Patients
with CLL and Coexisting Conditions
G-Clb
(n = 333)
R-Clb
(n = 329)
p-value
Overall response rate
78.4%
65.1%
<0.001
Complete response
20.7%
7.0%
—
Minimal residual diseasenegative in blood
37.7%
3.3%
<0.001
26.7 mo
15.2 mo
<0.001
Efficacy Endpoint
Median progression-free survival
Grade ≥3 Adverse Events
Infusion-related reactions
Neutropenia
Infections
G-Clb
20%
33%
12%
Goede V et al. N Engl J Med 2014;370:1101-10.
R-Clb
4%
28%
14%
FDA Approves the Use of Ofatumumab in
Combination with Chlorambucil for CLL
“On April 17, 2014, the US Food and Drug Administration
(FDA) approved ofatumumab in combination with
chlorambucil, for the treatment of previously untreated
patients with CLL, for whom fludarabine-based therapy is
considered inappropriate, based on results from a Phase III
study (COMPLEMENT 1) which demonstrated statistically
significant improvement in median PFS in patients who
received the combination of ofatumumab and chlorambucil
compared to patients who received chlorambucil alone.”
• Median Progression-Free Survival: 22.4 vs 13.1 months
http://www.cancer.gov/cancertopics/druginfo/fda-ofatumumab
Discussion Point
Recent FDA approval of ibrutinib;
available data and ongoing
investigation of lenalidomide and other
small-molecule B-cell inhibitors
Lenalidomide/Rituximab (R2) Salvage Treatment
for Relapsed/Refractory CLL
• N = 59 patients with a median of 2 prior treatments
(range: 1-9)
• Overall response rate
– Complete response
– Nodular partial response
66%
12%
12%
• Time to treatment failure
17.4 months
• Estimated survival at 36 months 71%
• Most common ≥Grade 3 adverse events:
– Neutropenia
73%
– Infection or febrile episode
24%
Badoux XC et al. J Clin Oncol 2013;31(5):584-91.
FDA Approves the Use of Ibrutinib in CLL
“On February 12, 2014, the US Food and Drug
Administration (FDA) granted accelerated approval to
ibrutinib for the treatment of patients with chronic
lymphocytic leukemia (CLL) who have received at
least one prior therapy, based on the results of a
multicenter single-arm trial of 48 patients with
previously treated CLL.”
• Overall response rate:
- Complete response:
- Partial response
with lymphocytosis:
Byrd JC et al. NEJM 2013;369:32-42.
http://www.cancer.gov/cancertopics/druginfo/fda-ibrutinib
71%
2%
20%
Discussion Point
Novel small molecules under
investigation in B-cell cancers:
PI3-kinase delta inhibitors (idelalisib),
anti-BCL2 inhibitors (ABT-199)
Idelalisib (GS-1101, CAL-101): BCR Signaling
Inhibitor
•
•
•
•
•
Oral inhibitor of PI3Kδ
Rapid and sustained reduction in lymphadenopathy in CLL
– Transient lymphocytosis
Bendamustine and/or rituximab + idelalisib in R/R CLL
– High ORR: ~80%
– 2-yr PFS: 63%
– 2-yr OS: 84%
Toxicities
– Febrile neutropenia
– Pneumonia
– Transaminase elevation
– Diarrhea
– Pyrexia
Ongoing Phase III studies
– NCT01539512: GS-1101/placebo + R
– NCT01569295: GS-1101/placebo + BR
Coutre SE et al. Proc ASH 2012;Abstract 191.
Mechanism of Action of Idelalisib
Idelalisib
Adapted from Woyach JA et al. Blood 2012;120(6):1175-84.
• 220 patients with decreased renal function, previous therapyinduced myelosuppression or major coexisting illnesses with
relapsed CLL received R/idelalisib or R/placebo
- Median PFS:
Not reached vs 5.5 mo
- Overall response rate:
81% vs 13%
- 12-month overall survival:
92% vs 80%
Mechanism of Action of ABT-199
• Many tumors, particularly lymphoid malignancies, are
addicted to BCL-2 for survival.
• ABT-199 is specific for BCL-2 and induces selective
death of BCL-2-dependent tumor cells while sparing
platelets, which depend primarily on BCL-XL
for survival.
Davids MS, Letai A. Cancer Cell 2013;23(2):139-41.
ABT-199: A Potent and Selective BCL-2 Inhibitor
• Oral, small molecule inhibitor of BCL-2
• Binds with high affinity to BCL-2 and with substantially
lower affinity to other BCL-2 proteins (BCL-XL, BCL-W
and MCL-1)
• Demonstrated preclinical activity as a single agent in a
wide range of hematologic cancer
• Main toxicities reported in relapsed/refractory NHL:
– Primarily Grade 1/2 (minimal Grade 3/4)
– Diarrhea, nausea, fatigue, pyrexia, upper respiratory
tract infection, neutropenia, cough
• Antitumor activity in multiple NHL histologies, including
100% best response rate in MCL
Davids MS et al. Proc ASCO 2013;Abstract 8520.
Two Patients with Follicular Lymphoma (FL)
Who Received Rituximab/Chemotherapy
Followed by Rituximab Maintenance
• 48 yo man with FL and multiple health problems
related to chronic obesity
(Ms Goodrich)
• 56 yo man with FL and comorbid communityacquired clostridium difficile infection
(Ms Rogers)
Case 3 (from the practice of Ms Goodrich)
• A 48-year-old chronically obese man diagnosed with
Stage IIIB, Grade I FL in 2007 with dermal involvement
and ascites received weekly rituximab x 8
• He experienced some symptomatic response but lost
approximately 100 pounds due to his disease
• He received R-CVP then R-EPOCH and achieved a
PET-negative complete response (CR)
• He remained in CR until 2011, when a biopsy-proven
recurrence was observed
• He received BR followed by 2 years of maintenance
rituximab
• Currently he is being observed off treatment
• He has regained the weight he lost and has multiple
health issues related to his obesity
Pre-Bendamustine/R: Right Axillary Adenopathy
Post-Bendamustine/R: Right Axillary Adenopathy
Discussion Point
Complications of oncologic care in
patients with morbid obesity
Discussion Point
“Watchful waiting” in FL; role of
rituximab monotherapy
Discussion Point
Commonly used induction regimens for
patients receiving active treatment for FL
(eg, R-CHOP, bendamustine/R, R-CVP)
StiL NHL 1-2003 Phase III Study
Bendamustine
+ Rituximab (BR)
Eligibility
• Untreated indolent NHL
or MCL (N = 549)
R
R-CHOP
Median PFS: 69.5 mo (BR) vs 31.2 mo (R-CHOP)
Rummel MJ et al. Lancet 2013;381;1203-10.
Key Findings from StiL NHL 1-2003
• Median follow-up: 45 months
• BR vs R-CHOP
– Median PFS (all pts): 69.5 vs 31.2 months
– Median PFS (FL pts): 39% reduction in risk of
progression
BR
• Erythematous
skin reactions
Rummel MJ et al. Lancet 2013;381;1203-10.
R-CHOP
• Alopecia
• Infections
• Peripheral neuropathy
• Stomatitis
• Hematologic toxicity
BRIGHT Phase III Study
Bendamustine +
Rituximab (BR)
Eligibility
Untreated indolent NHL
or MCL (N = 447)
R
R-CHOP or
R-CVP
Complete Response Rate: 31% (BR) vs 25% (R-CHOP or R-CVP)
Overall Response Rate: 97% (BR) vs 91% (R-CHOP or R-CVP)
Flinn IW et al. Blood 2014;[Epub ahead of print].
Key Findings from the BRIGHT Study
BR vs R-CHOP or R-CVP
– Complete response rate: BR noninferior to
R-CHOP/R-CVP (31% vs 25%)
– Overall response rate (97% vs 91%)
BR
• Lymphopenia
• Nausea/vomiting
• Drug hypersensitivity
Flinn IW et al. Blood 2014;[Epub ahead of print].
R-CHOP or R-CVP
• Alopecia
• Neutropenia
• Leukopenia
• Peripheral neuropathy
Discussion Point
Use of rituximab maintenance for
patients who receive
rituximab/chemotherapy: Duration of
treatment and potential complications
Clinical Issues with the Use of Rituximab
• Infusion-Related Adverse Reactions
• Administration and Dosing
– 90-minute versus standard infusion
• Phase 3 RATE study (Proc ASH 2011;Abstract 2703)
• FDA approved on October 19, 2012 starting cycle 2
for patients with NHL who did not experience a Grade
3 or 4 infusion-related adverse reaction during cycle 1
– Fixed-dose subcutaneous versus standard intravenous
infusion
• Phase 3 SABRINA study (Lancet Oncol 2014)
• Long-Term Safety
– Hypogammaglobulinemia
– Risk of persistent infections
For your patients receiving R maintenance therapy,
do you generally switch to rapid infusion rate R
(90 minutes) after no complications with an initial
standard-rate infusion?
% of respondents
Research To Practice Patterns of Care Study January 2014 (N = 101 practicing oncologists)
Discussion Point
Available research data with the
“R-squared regimen”
(lenalidomide/rituximab) and an
ongoing Phase III trial comparing it to
rituximab chemotherapy
Lenalidomide and Rituximab for
Untreated Indolent Lymphoma: Final
Results of a Phase II Study
Fowler NH et al.
Proc ASH 2012;Abstract 901.
Patients with FL (N = 46)
ORR
Complete Response
Estimated 2-yr PFS
98%
87%
89%
≥Grade 3 Neutropenia
40%
RELEVANCE Phase III Study
Target Accrual: 1,000 (Active, recruiting)
Lenalidomide +
Rituximab
Eligibility
• Grade I, II or IIIa
untreated Stage II-IV FL
• In need of treatment
R
R-CHOP, R-CVP
or BR
PR or CR
Maintenance R
q2m x 12
www.clinicaltrials.gov, April 2014
ClinicalTrials.gov Identifier: NCT01650701
Case 4 (from the practice of Ms Rogers)
• A 56-year-old man was diagnosed with Grade I FL and
received rituximab monotherapy
• He complained of continued fatigue and malaise, had a
PET/CT scan and was incidentally diagnosed with
thyroid cancer
• He underwent a thyroidectomy and radioisotope
treatment with a tracheostomy still in place
• He then received BR for the FL and is currently
receiving maintenance rituximab
• He has been unable to work because of issues related
to a community-acquired clostridium difficile infection
and the placement of a tracheostomy tube
• Overall, he has a positive outlook and has coped well
with his situation
Avid Area of Thyroid on PET (May 2012)
PET (May 2012): Mesenteric Adenopathy with SUV 10.8
Patient also had retroperitoneal adenopathy that was not metabolically active
Discussion Point
Diagnosis of a second primary tumor
while receiving initial treatment for
cancer
A Patient with Angioimmunoblastic T-Cell
Lymphoma (TCL) and a Patient with ALK-Negative
Anaplastic Large Cell Lymphoma (ALCL)
• 53 yo man with rapidly progressive disease
(Ms Goodrich)
• 65 yo man who delayed allogeneic STC and had
rapid disease progression (Ms Rogers)
Case 5 (from the practice of Ms Goodrich)
• A 53-year-old man was diagnosed with
angioimmunoblastic TCL
• Workup revealed extensive lymphadenopathy and
parenchymal lung, spleen, bone marrow and skin
involvement
• He received CHOEP and achieved a CR lasting 2
months before rapid disease progression
• He then received ICE in preparation for allogeneic
SCT and achieved a partial response after 2 cycles
but experienced disease progression after cycle 3
• He responded to 2 cycles of pralatrexate followed
by rapid disease progression
Discussion Point
Diagnosis and management of
common presentations of TCL
Classification of PTCL
• PTCL is a heterogeneous group of aggressive mature T-/NK-cell lymphomas
• CTCL is a subgroup of PTCL consisting of several diseases that originate in
the skin and are primarily slow growing
PTCL (Mature T-/NK-cell
Neoplasms)
Cutaneous
Extranodal
Nodal
Mycosis Fungoides
(MF)
NK/TCL
Nasal Type
Peripheral TCL-NOS
Transformed
MF
EnteropathyAssociated TCL
Anaplastic Large Cell
Lymphoma (ALK +/-)
Sézary Syndrome
Hepatosplenic
TCL
Angioimmunoblastic
TCL
Primary Cutaneous
CD30+ T-Cell
Disorders
Subcutaneous
Panniculitis-Like TCL
Leukemic
Adult T-Cell
Leukemia/Lymphoma
Aggressive NK-Cell
Leukemia
T-Cell Prolymphocytic
Leukemia
T-Cell Large Granular
Lymphocytic Leukemia
Primary Cutaneous
Gamma/Delta TCL
Aggressive
Indolent
Adapted from Swerdlow SH et al. WHO Classification of Tumours of Haematopoietic and
Lymphoid Tissues 2008.
Possible Side Effects Associated with
Romidepsin and Pralatrexate
Romidepsin
• Thrombocytopenia
• Neutropenia
• Anemia
• Infections
• QT interval prolongation
Pralatrexate
• Thrombocytopenia
• Neutropenia
• Anemia
• Mucositis
• Skin reactions
• 19% of patients with PTCL
discontinued therapy due
to an adverse event1
• 23% of patients with PTCL
discontinued therapy due to
an adverse event2
B et al. J Clin Oncol 2012;30(6):631-6; 2 O’Connor OA et al. J Clin Oncol
2011;29(9):1182-9; Romidepsin Patient Package Insert; Pralatrexate Patient Package Insert.
1 Coiffier
Case 6 (from the practice of Ms Rogers)
• A 65-year-old man with ALK-negative ALCL whose
disease relapsed on multiple treatments, including
CHOP, pralatrexate, DHAP and radiation therapy
• He received brentuximab vedotin on a clinical trial,
which caused a clinical response but peripheral
neuropathy that was addressed with dose
adjustments, and after completing 16 cycles he
was in CR
• His disease recurred while he was considering
allogeneic SCT
2008: Neoplasm in calf
2010: Left hilar mass
Mechanism of Action of Brentuximab Vedotin
Brentuximab vedotin is an antibody drug conjugate (ADC)
targeted to cells expressing CD30 on their surface
1 ADC binds to CD30 and
initiates internalization of
the ADC-CD30 complex
2 MMAE is released
3 MMAE binds to tubulin
and disrupts the
microtubule network
4 Cell cycle arrested
5 Apoptosis (cell death)
Courtesy of Julie M Vose, MD, MBA.
Ongoing Phase III ECHELON-2 Trial Design
(NCT01777152)
1:1 randomization
Target accrual (n = 300)
Newly diagnosed CD30-positive
MTCL
Fluorodeoxyglucose (FDG)-avid
disease by PET
R
Measurable disease ≥1.5 cm by
CT
Brentuximab/CHP
Every 3 weeks
6-8 cycles
CHOP
Every 3 weeks
6-8 cycles
Study start date: January 2013
Estimated study completion date: December 2019
Brentuximab vedotin dose: 1.8 mg/kg (IV)
• Primary endpoint: Progression-free survival (PFS) by independent review
• Secondary endpoints include: PFS in sALCL by independent review, complete
remission rate, overall survival, objective response rate, safety
O’Connor OA et al. Proc ICML 2013;Abstract 138; Proc ASCO 2013;Abstract TPS8611.