New Opportunities to Enhance the Clinical
Outcomes of Patients With Follicular
Lymphoma
Bruce D. Cheson, MD
Head of Hematology
Deputy Chief, Hematology/Oncology
Georgetown University Hospital
Lombardi Comprehensive Cancer Center
Jointly Provided by
Disclosure of Conflicts of Interest
Bruce D. Cheson, MD discloses the following
commercial relationships:
– Advisor/consultant: Astellas, AstraZeneca, Celgene,
Gilead, Merck, Pharmacyclics, Pfizer,
Roche/Genentech, Seattle Genetics, and Spectrum
Pharmaceuticals
– Research support: AbbVie, Acerta, Celgene, Gilead,
Medimmune, Pharmacyclics, Roche/Genentech,
Seattle Genetics, and Teva
Learning Objectives

Outline patient- and disease-related
characteristics that influence selection of
appropriate treatment for follicular lymphoma

Differentiate efficacy and safety data on novel
therapies for previously untreated and
relapsed/refractory follicular lymphoma

Evaluate methods to assess response to
follicular lymphoma treatment
Relative Incidence of NHL Subtypes
>71,000 new cases in US in 2015
LL
2%
Burkitt’s-like
2%
LPL
1%
Composite
13%
ALCL
2%
DLBCL
32%
PMLBCL
2%
MZL
6%
PTCL
6%
MCL
6%
NHL = non-Hodgkin lymphoma.
Armitage & Weissenburger, 1998; ACS, 2015.
FL
22%
SLL
6%
Follicular Lymphoma
Photo courtesy of Randy D. Gascoyne, MD.
Follicular Lymphoma Pathogenesis

t(14;18) gives rise to BCL2-IGH fusion in BM

50-75% of normals harbor low levels of
circulating t(14;18)+ cells

Most never develop FL, indicating that BCL2
ectopic expression is necessary but not
sufficient

Expanding population of atypical B cells from
GC, share genotypic and phenotypic features of
FL
Roulland et al, 2014.
Pathogenesis of FL
GC = germinal center; SHM/CSR = somatic hypermutation/class switch recombination; FLIS = follicular lymphoma in situ.
Swaminathan & Müschen, 2014.
t(14;18) as a Predictive Biomarker for FL

520,000 healthy participants on EPIC study

100 developed FL 2-161 months after enrollment

Clonal analysis - FL developed from pre-existing
t(14;18)+ committed precursors

23-fold increased risk of FL in samples with a
frequency >1/10,000 blood cells

Those who developed FL had a higher prevalence
of t(14;18) versus controls (P<0.001)

Genes involved in transforming process under study
Roulland et al, 2014.
Overall Survival According to FLIPI:
Clinical Prognostic Factors
1.0
L Elevated LDH
A Age ≥60
S Stage III/IV
H Hemoglobin <120 g/L
Survival probability
No Nodal regions 4
Low risk
0.8
Intermediate risk
0.6
High risk
0.4
0.2
P<10-4
0
0
1
2
3
4
5
6
7
Years
Risk Group
Low
Intermediate
High
No. of Factors
% of Patients
5-Yr OS (%)
10-Yr OS (%)
0-1
36
90.6
70.7
2
37
77.8
50.9
3-5
27
52.5
35.5
FLIPI = Follicular Lymphoma International Prognostic Index; LDH = lactate dehydrogenase; OS = overall survival.
Solal-Céligny et al, 2004.
Initial Treatment of Advanced FL:
Current Challenges

When to treat

Optimal induction regimen

Role of postinduction strategies

Integration of new agents

Need for surrogate end points
WW vs. Clb in Advanced Stage
Asymptomatic Untreated FL
WW = watch and wait.
Ardeshna et al, 2003.
Rituximab vs. WW as Initial Treatment for
Asymptomatic FL
Ardeshna et al, 2014.
Criteria for High Tumor Burden FL
 Maximum
 >3
diameter >7 cm
sites with a diameter of >3 cm
 Systemic
symptoms
 “Substantial”
 Serious
 Risk
spleen involvement
effusions
of local compression symptoms
 Circulating
lymphoma cells
 Peripheral
blood cytopenias
Brice et al, 1997.
Impact of Rituximab on OS in Frontline
Follicular NHL
Herold et al, 2007.
Hiddemann et al, 2005.
Marcus et al, 2008.
FOLLO5: Time to Treatment Failure
and Progression-Free Survival
B 100
100
Progression-Free
Survival (%)
Treatment Failure (%)
A
80
60
40
20
0
R-CVP
R-CHOP
R-FM
Federico et al, 2013.
60
40
20
6 12 18 24 30 36 42 48 54 60
Time (months)
No. at risk
R-CVP
168 136 119 95
R-CHOP 165 147 137 120
R-FM
171 150 139 120
80
74
83
95
51
66
68
36
47
50
23
32
32
13
19
20
5
12
12
1
5
4
0
R-CVP
R-CHOP
R-FM
6 12 18 24 30 36 42 48 54 60
Time (months)
No. at risk
R-CVP
168 154 136 108 85 60
R-CHOP 165 157 147 128 89 70
R-FM
171 163 151 130 101 73
41
51
55
27
36
36
14
22
23
6
14
14
1
6
5
FOLL05: Grade 3/4 Toxicities by Arm
63.7
60
Anemia
Neutropenia
Thrombocytopenia
Infections
49.7
P=0.089
P<0.001
P<0.001
P=0.527
40
28.0
20
0.6
0
Federico et al, 2013.
7.7
3.1 4.2
3.1
4.8
4.7
2.4
2.5 3.1
Thrombocytopenia
Infections
0.0
Anemia
Neutropenia
R-CVP
R-CHOP
R-FM
Overall Survival in FL:
Lymphocare Data
Nasoupil et al, 2015.
BR vs. R-CHOP in Untreated FL: PFS
Rummel et al, 2013.
BR vs. R-CHOP: Heme Toxicity
Rummel et al, 2013.
BR vs. R-CHOP Non-Heme Toxicities
Rummel et al, 2013.
BRIGHT Study Design
*Up to eight cycles at investigator discretion.
Finn et al, 2014.
BRIGHT: Response Rates
IRC Assessment of
Response by
Histology, n/N (%)
CR
CR + PR
BR
R-CHOP/R-CVP
BR
R-CHOP/R-CVP
iNHL
49/178 (28)
43/174 (25)
173/178 (97)
160/174 (92)
FL
45/148 (30)
37/149 (25)
147/148 (>99)
140/149 (94)
MZL
5/25 (20)
4/17 (24)
23/25 (92)
12/17 (71)
LPL
0/5
1/6 (17)
3/5 (60)
6/6 (100)
17/34 (50)
9/33 (27)a
32/34 (94)
28/33 (85)a
MCL
aR-CHOP,
n=22.
IRC = independent review committee; iNHL = indolent NHL; CR = complete response; PR = partial response.
Finn et al, 2014.
BRIGHT: Grade ≥3 Adverse Events
Grade ≥3 AEs (occurring in ≥3% of
patients), n (%)
Hematologic
BR (n=103)
R-CHOP (n=98)
BR (n=118 )
Preselected for R-CVP
(n=116 )
White blood cell count
33 (32)
71 (72) a
51 (43)
44 (38)
Absolute neutrophil count
40 (39)
85 (87) a
58 (49)
65 (56)
Lymphocyte count
63 (61)
32 (33) a
74 (63)
32 (28)a
0
3 (3)
6 (5)
6 (5)
Platelet count
10 (1)
12 (12)
6 (5)
2 (2)
Nausea
3 (3)
0
1 (<1)
0
Vomiting
5 (5)
0
2 (2)
0
Abdominal pain
2 (2)
3 (3)
0
3 (3)
Drug hypersensitivity
3 (3)
0
2 (2)
0
Fatigue
4 (4)
2 (2)
4 (3)
1 (<1)
Pneumonia
2 (2)
0
5 (4)
1 (<1)
Infusion-related reaction
6 (6)
4 (4)
7 (6)
4 (3)
12 (12)
5 (5)
8 (7)
8 (7)
Hyperglycemia
0
2 (2)
1 (<1)
5 (4)
Back pain
0
1 (1)
0
4 (3)
Syncope
1 (<1)
0
0
3 (3)
Dyspnea
2 (2)
2 (2)
3 (3)
1 (<1)
Hemoglobin
Nonhematologic
Infection
aP<0.0001.
AEs = adverse events.
Finn et al, 2014.
Preselected for R-CHOP
PRIMA Study Design
INDUCTION
MAINTENANCE
Rituximab maintenance
375 mg/m2
every 8 weeks
for 2 years
Registration
High
tumor burden
untreated
follicular
lymphoma
Immunochemotherapy
8 x rituximab
+
8 x CVP or
6 x CHOP or
6 x FCM
CR/CRu
PR
PD/SD
off study
Random 1:1
Observation
5 YEARS FOLLOW-UP
CRu = Complete response unconfirmed; PD = progressive disease; SD = stable disease.
Salles et al, 2013.
PRIMA 6-Year Follow-Up:
2-Year R Maintenance Shows Benefit
R = Rituximab.
Salles et al, 2013.
Overall Survival by Maintenance
Hochster et al, 2009.
Martinelli et al, 2010.
Ardeshna et al, 2010.
Salles et al, 2011.
RESORT Study Design
Rituximab
375 mg/m2
qw  4
aContinue
CR or PR
R
A
N
D
O
M
I
Z
E
Rituximab
Maintenancea
375 mg/m2
q 3 months
Rituximab
retreatment at
progressiona
375 mg/m2 qw  4
until treatment failure
• No response to retreatment or PD within 6 months of R
• Initiation of cytotoxic therapy or inability to complete rx
Kahl et al, 2014.
RESORT: Time to Treatment Failure
Kahl et al, 2014.
Indications for Hematopoietic Stem Cell
Transplant in FL
Montoto et al, 2013.
SAKK 35/10 Study Design

Phase II study of frontline R vs. R2 in FL grades 1, 2, and 3a and requiring systemic
therapy

Primary end point: CR/CRu at week 23a
– Study goal: 20% increase for R2 over R with 90% power and type I error (α) of
0.10

Secondary end points: ORR, DOR, PFS, OS, and safety
Previously untreated
FL (N=154)
• Histologically
confirmed FL grades
1, 2, and 3A
aTreatment
R2 (n=77): rituximab (see below) +
lenalidomide
15 mg/d PO for 19 weeks total
(2 weeks prior, 15 weeks during,
and 2 weeks after rituximab)
Rituximab (n=77)
375 mg/m2, Day 1 of Weeks 1, 2, 3,
4, 12, 13, 14, and 15
discontinued Week 10 if <25% reduction in sum of product of tumor diameters.
ORR = overall response rate; DOR = duration of response; NCI = National Cancer Institute.
Kimby et al, 2014.
Response per
NCI Cheson 1999
criteria
Frontline R2 vs. R in FL (SAKK 35/10):
Overall Response Rate
Week 10
P<0.0001
100%
Week 23
P=0.002
90%
81%
80%
75%
Patients ( %)
70%
61%
60%
50%
45%
45%
62%
40%
30%
PR
36%
CR/CRu
35%
20%
36%
25%
10%
10%
13%
Rituximab
(n = 77)
R2
(n = 77)
0%
Kimby et al, 2014.
Rituximab
(n = 77)
R2
(n = 77)
SAKK 35/10: Safety
Adverse Events
(>1 patient), n (%)
R2 (n=77)
Rituximab (n=76)
Grade 3
Grade 4
Grade 3
Grade 4
Neutropenia
−
1 (1)
11 (14)
4 (5)
Thrombocytopenia
−
−
2 (3)
1 (1)
Suicide attempt
−
1 (1)
−
−
Hypertension
3 (4)
−
7 (9)
−
Fatigue
1 (1)
−
2 (3)
−
Maculopapular rash
−
−
4 (5)
−
Allergic reaction
−
−
2 (3)
−
UTI
−
−
2 (3)
−
Depression
−
−
−
1 (1)
Psychosis
−
−
−
1 (1)
Treatment was discontinued by 21 patients (28%) in arm R, in 16 due to lack of response at Week 10
and in 1 due to toxicity, and by 19 patients (25%) in arm R2, in 3 due to lack of response at Week 10
and in 13 due to toxicity.
UTI = urinary tract infection.
Kimby et al, 2014.
CALGB 50803: R2 in Previously
Untreated FL
Overall
N=55
FLIPI 0-1
n=16
FLIPI 2
n=35
FLIPI 3
n=2
FLIPI
Unknown
n=2
ORR
53 (96%)
16 (100%)
33 (94%)
2
(100%)
2 (100%)
CR
39 (71%)
12 (75%)
24 (69%)
2
(100%)
1 (50%)
PR
14 (25%)
4 (25%)
9 (26%)
-
1 (50%)
SD
2 (4%)
0 (0%)
2 (6%)
-
-
Four additional patients in PET CR but not confirmed by bone marrow biopsy.
There was no significant association between CR rate and FLIPI score, presence
of bulky disease, or grade.
PET = positron emission tomography.
Martin et al, 2014.
CALGB 50803:
Response Characteristics





Median follow-up = 2.3 years
Median time to first response = 10 weeks
Median time to complete response = 10 weeks
92% of PET negative CRs occurred by 24 weeks
8/65 evaluable patients have progressed so far
– 2 stopped after 1-2 cycles due to toxicity
– 2 had achieved a best response of CR
– No patients have died
Martin et al, 2014.
CALGB 50803: Progression-Free Survival
0 .6
0 .4
0 .0
0 .2
P ro b a b ilit y
0 .8
CALGB 50803
Progression-Free Survival
0.0
0.5
1.0
1.5
Years from Study Entry
Martin et al, 2014.
2.0
2.5
3.0
Unmet Needs in Frontline FL
 PET
positive after induction
 Early
 How
relapses
to integrate novel agents
 Surrogate
end points
1.0
100
80
0.8
Probability
R-CHOP
60
40
20
0
0
6
12
B-R
0.6
0.4
R-CHOP
Press et al (2013). SWOG S0016. 0.2
J Clin Oncol.
0.0
18 24 30 36 42 48 54 60
0
Time (months)
1.0
This suggests a high-risk group
of patients who will relapse
early despite different treatment
approaches including
maintenance.
Event-Free Rate
Progression-Free Survival (%)
20% of Patients With FL Experience Disease Progression
Within 24 Months of Chemoimmunotherapy
Rummel el al (2013). Lancet.
6
12
18
24 30 36 42
Time (months)
48
54
60
Rituximab maintenance
0.8
0.6
0.4
0.2
Salles et al (2011). PRIMA
Lancet.
0.0
0
Casulo et al, 2013.
6
12
18
24 30 36 42
Time (months)
48
54
60
Distribution of Characteristics by Group
Characteristic
Early
Progressor
Reference
Group
Significancea
Grade 3 histology
34%
40%
P=0.50
High-risk FLIPI
57%
40%
P=0.01
Elevated LDH
43%
28%
P=0.01
Low Hgb
35%
22%
P=0.01
≥2 nodal sites
40%
25%
P=0.01
Poor ECOG PS
16%
4%
P<0.01
aX2.
ECOG PS = Eastern Cooperative Oncology Group performance status.
Casulo et al, 2013.
OS of Patients With FL Who Relapsed
Within 2 Years of R-CHOP (“Early POD”)
122 patients were classified as early progressors
(n=110 POD and n=12 non-POD deaths within 2 years)
Survival probability
1.0
0.8
Reference Group
0.6
Early Progressor
0.4
0.2

2-year OS (95% CI) was 71% (61.5-78.0)

5-year OS (95% CI) was 50% (40.3-58.8)
0.0
0
Patients at risk:
Early
122
Reference 420
CI = confidence interval.
Casulo et al, 2013.
1
2
3
101
420
78
420
69
407
4
5
6
Time (years)
58
49
45
387
363
344
7
8
9
10
33
252
14
144
6
33
0
0
Postinduction Response Assessment With
PET/CT: Limitations to These Studies…
PRIMA: 122 Patients 2004-2010
Trotman et al (2011). J Clin Oncol.

Hypothesis generating

Retrospective analysis of local PET interpretation within a prospective study with independent CT
assessment
Results confirmed by independent scan review of 61 patients

FOLL05: 202 Patients 2005-2010
Tychyj-Pinel et al (2014). EJNMMI.
Luminari et al (2013). Ann Oncol.

Retrospective analysis of local PET reports within a prospective study with local CT assessment

Prospective standardized PET acquisition/assessment in accordance to the 5-Point Scale, with
local CT assessment
Shorter follow-up

PET Folliculaire: 106 Patients 2007-2009


Dupuis et al (2012). J Clin
Oncol.
Prospective standardized PET acquisition/assessment in accordance to the 5-Point Scale, with
local CT assessment
Shorter follow-up
PFS According to CT Response
SD/PD vs.
• PR, HR 4.2
• CRu, HR 5.6
• CR, HR 7.8, P<0.0001
PR vs.
• CR/CRu, HR 1.7 (1.1-2.5),
P=0.02
CRu/PR vs.
• CR, HR 1.6 (1.1-2.4),
P=0.02
CT = computed tomography.
Trotman et al, 2014.
Both PET Cut-Offs Predictive of PFS
Score ≥3
Score ≥4
63%
23%
HR 3.9 (95% CI 2.5-5.9, P<0.0001)
Median PFS: 16.9 (10.8-31.4) vs. 74.0 months (54.7-NR)
Trotman et al, 2014.
Postinduction PET Status (Cut-Off ≥4)
and Overall Survival
97%
87%
HR 6.7, 95% CI 2.4-18.5, P=0.0002
Median OS: 79 months vs. NR
Trotman et al, 2014.
MRD Predicts Progression-Free
Survival in FL
 DNA
from BM from 415 pts from FOLLO-5
 Assessed
for BCL2/IGH at diagnosis,
posttreatment, and at 12 and 24 months
 Marker
 Those
detected in 53% pretreatment
without or with low levels had
higher CR rates and longer PFS
MRD = minimal residual disease.
Galimberti et al, 2014.
PFS From Randomization Longer in Pts Without
BCL2/IGH Rearrangement During Follow-Up
Independent of Quality of Responsea
aP=0.001.
Galimberti et al, 2014.
PFS From Randomization Significantly Longer in
Pts Without BCL2/IGH Detectable After 12 Months
of Follow-Upa
aP=0.015.
Galimberti et al, 2014.
Relapsed vs. Refractory FL

Relapsed
– Initial response (CR or PR)
– Progress >6 months following completion of standard
induction therapy

Poor risk relapse
– PET/CT scan positive postinduction
– <12 months following treatment

Refractory
– <PR to standard induction
– CR or PR that lasts <6 months
PET/CT = positron emission tomography/computed tomography.
NCCN, 2015.
US Bendamustine Trials

Two phase II, multicenter, single-agent studies

Relapsed, follicular, and low-grade

Refractory to rituximab: progression <6 months
– First dose of rituximab
– Completion of rituximab maintenance
– Completion of chemotherapy + rituximab

Dosage: bendamustine 120 mg/m2 IV over 3060 minutes, Days 1 and 2 every 21 days x 6
cycles
Cheson et al, 2009.
US Bendamustine Trials
 N=176
 Median
age 61 years (range, 31-84)
 Histologies:
FL ( 68%), SLL (20%), MZL
(11%), and LPL (1%)
 Stage
III-IV in 81%
 Median
 34%
Cheson et al, 2009.
three prior chemotherapy regimens
refractory to last chemotherapy
US Bendamustine Trials: Response
in Rituximab-Refractory Patients
Patient Group
(N=161)
Overall
FLIPI - Low
Int
High
Alkylating agent
Sensitive
Refractory
Purine analog
Sensitive
Refractory
Cheson et al, 2010.
ORR
(%)
CR/CRu
(%)
76
77
75
79
23
17
28
27
88
59
28
12
81
60
25
20
Bendamustine-R in Relapsed iNHL:
% Response Rate by Histology
Response
Category
All Patients
Indolent
Lymphoma
Mantle Cell
Lymphoma
ORR
92
93
92
CR
41
41
42
CRu
14
13
17
PR
38
39
33
SD
8
7
8
PD
0
0
0
Robinson et al, 2008.
Bendamustine-R in Relapsed iNHL:
Progression-Free Survival
Cheson et al, 2010.
New Targeted Agents
Agent
Target
Daratumumab
CD38
Polatuzumab vedotin
CD79b
Ibrutinib
Btk
ACP-196
Btk
GS-9973
Syk
Idelalisib
PI3-K
GS9901
PI3-K
IPI-145
PI3-K
Nivolumab
PD-1
Pembrolizumab
PD-1
Pidilizumab
PD-1
ABT-199
Bcl-2
Selinexor
XP01 (Nuclear transport)
B-Cell Receptor
Cell Proliferation, Migration, Growth, Survival
Young & Staudt, 2013.
Ibrutinib Monotherapy In
Relapsed/Refractory FL (n=40)
 Responses:
 2 CRs and 9 PRs by CT criteria
 Three patients with PR and 1 with
SD were PET/CT negative at C3D1
 72% of patients had reduction in
tumor volume
 Median time to response:
2.8 months (range, 1.8-7.4)
 1-year PFS 50.1% (95% CI 35.3-
71.1)
 Median follow-up 10.2 months
 C1D8 SUVmax correlates with
response (P=0.04) and PFS
(P=0.003)
Bartlett et al, 2014.
61
101-09: Overall Response Rates by
Disease Subgroups
June 2013
Complete Response
June 2014
Partial Response
Minor Response
2%
n=2
8%
n=10
Stable Disease
6%
n=7
50%
n=63
10%
n=12
Overall
Response
n=72/125
33%
n=41
47%
n=59
(95% CI:
47.6–65.6)
1%
n=1*
Not evaluable
58%
8%
n=10
Overall
Response
n=71/125
34%
n=42
Progressive Disease
2%
n=2
57%
(95% CI:
48.4–66.4)
1%
n=1*
Overall Response Rate By Disease Subgroups: 2014
Complete
Response
Partial
Response
Minor
Response
Stable
Disease
Progressive
Disease
Not
evaluable
ORR, % (95% CI)
14%
n=10
FL
n=72
SLL
n=28
4%
n=1
MZL
n=15
7%
n=1
42%
n=30
32%
n=23
57%
n=16
36%
n=10
40%
n=6
0%
20%
40%
10%
n=1
60%
*LPL/WM = lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patient.
Gopal et al, 2014.
1%
n=1
4%
n=1
47%
n=7
70%
n=7
LPL/WM
n=10
8%
n=11
10%
n=1
80%
56% (43–67)
61% (41–79)
7%
n=1
47% (21–73)
10%
n=1
80% (44–98)
100%
101-09: Progression-Free Survival
PFS 2014 (All Patients)*
PFS 2014 (By Disease Group)
2014 Median PFS: 11.0 months
*Includes patients who achieved a CR or PR (or MR for LPL/WM)
according to IRC assessments
Gopal et al, 2014.
Patients
at risk, n
72
28
15
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4
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Role of PD-L1 in Antitumor
Immune Response
4
IFN! -mediated
up-regulation of
tumor PD-L1
PD-L1/PD-1-mediated
Inhibition of
tumor cell killing
receptor
Priming and Activation
of T cells
Immune cell
modulation of T cells
Stromal PD-L1
modulation of T cells
Chen DS, Irving BA, Hodi FS.
Clin Cancer Res. 2012;18:6580.
PD-L2 mediated inhibition
of TH-2 T cells
PD-L1 plays an important role in dampening
the anti-tumor immune response
CONFIDENTIAL INFORMATION – DO NOT COPY OR FORWARD
Chen et al, 2012.
Nivolumab in Lymphoma
Leskin et al, 2014
Risk of Transformation in FL
Montoto et al, 2011.
Survival Following Transformation
Montoto et al, 2007.
Key Takeaways
 Follicular
lymphoma is a heterogeneous
disease
 Need
biomarkers to distinguish among
subtypes
 Treatment
goals
– Move towards noncytotoxic approaches
– Individualized strategies
– Cure
Case Study 1: Initial Treatment of FL






70-year-old woman with a history of a herniated disc was having a routine
follow-up CT scan, which revealed:
– Left-sided hydronephrosis caused by a nodal mass 11.1 x 10.5 cm
– Inguinal, paraaortic, and portacaval adenopathy adenopathy
– Spleen enlarged at 15 cm
Laboratory studies showed a mild anemia and creatinine of 2.4 mg/dL
Fine needle aspiration of her enlarged right inguinal node was
nondiagnostic. Subsequent excisional lymph node revealed grade 1/2 FL
When questioned carefully, patient reported 5 pounds of unintentional
weight loss, a sense of abdominal fullness, but no fevers or night sweats
Bone marrow biopsy revealed 10% involvement by FL
Now patient’s performance status is 2. CBC reveals a hematocrit of 32%,
absolute neutrophil count of 750/mm3, and platelets of 80,000/mm3. Bone
marrow biopsy reveals 30% infiltration by FL
Case Study 1: Initial Treatment of FL
Which initial treatment approach would you
recommend for this patient?
a.
Watch and wait
b.
Rituximab monotherapy
c.
R-CHOP
d.
R-bendamustine
Case Study 2: Relapsed FL

Previously healthy 68-year-old man presented with complaints of
fatigue, drenching night sweats, a 10-pound weight loss, and a mass
in his neck

CT scan revealed diffuse lymphadenopathy and PET scan
confirmed FDG-avidity with standard uptake values in the range of
6-12. One of the brightest nodes was biopsied and the pathology
was interpreted as grade 2 FL

Received six cycles of R-CHOP to a complete remission that lasted
for 4 years. Subsequently experienced increasing adenopathy and
splenomegaly, with a return of symptoms. Bendamustine/rituximab
was administered for six cycles

Achieved a good partial response but experienced prolonged
neutropenia and thrombocytopenia. At approximately 12 months, at
age 73, his disease recurs
Case Study 2: Relapsed FL
Which treatment approach would you
recommend for this patient?
a.
Repeat R-CHOP
b.
R-ICE with autologous stem cell transplant
c.
Idelalisib
d.
Radioimmunotherapy with Y-90 ibritumomab
tiuxetan
Case Study 3: Refractory FL

A 56-year-old woman noticed new lumps around her neck, making it difficult to button
her blouse. She visited her primary care physician who, despite any other symptoms,
administered a series of antibiotics, with no resolution

Fine needle aspiration was non-diagnostic. Excisional biopsy revealed a diagnosis of
grade 3a FL

Patient was referred to an oncologist who completed staging:
–
Normal CBC and liver chemistries, with elevated LDH
–
PET/CT scan revealed diffuse adenopathy, with several nodal masses of 4-5 cm in the
axillae, abdomen, and retroperitoneum
–
Bone marrow biopsy showed 40% peritrabecular infiltration with small cleaved cells,
consistent with FL

Patient received bendamustine/rituximab for six cycles, which was well tolerated

Posttreatment PET/CT scan showed a moderate amount of persistent disease, with
only a 35% reduction in tumor volume. She declined stem cell transplant

As the patient was asymptomatic, the decision was made to watch and wait to
determine the pace of her disease. However, in 11 months, substantial progression
was noted
Case Study 3: Refractory FL
Which treatment approach would you
recommend for this patient?
a.
Clinical trial of a novel targeted therapy
b.
R-CHOP
c.
Rituximab/lenalidomide
d.
High-dose therapy with autologous stem cell
transplant
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