New Opportunities to Enhance the Clinical Outcomes of Patients With Follicular Lymphoma

Bruce D. Cheson, MDHead of Hematology

Deputy Chief, Hematology/OncologyGeorgetown 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

NHL = non-Hodgkin lymphoma.Armitage & Weissenburger, 1998; ACS, 2015.

Relative Incidence of NHL Subtypes

MZL6%

LPL1%

LL2%

ALCL2%

PMLBCL2%

Burkitt’s-like2%

PTCL6%

MCL6%

SLL

Composite13%

DLBCL32%

FL22%

>71,000 new cases in US in 2015

6%

Photo courtesy of Randy D. Gascoyne, MD.

Follicular Lymphoma

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.

GC = germinal center; SHM/CSR = somatic hypermutation/class switch recombination; FLIS = follicular lymphoma in situ.Swaminathan & Müschen, 2014.

Pathogenesis of FL

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.

Surv

ival

pro

babi

lity

Low risk

Intermediate risk

High risk

0

0.2

0.4

0.6

0.8

1.0

Years0 1 2 3 4 5 6 7

No Nodal regions 4

L Elevated LDH

A Age ≥60

S Stage III/IV

H Hemoglobin <120 g/L

Risk Group No. of Factors % of Patients 5-Yr OS (%) 10-Yr OS (%)Low 0-1 36 90.6 70.7

Intermediate 2 37 77.8 50.9

High 3-5 27 52.5 35.5

P<10-4

FLIPI = Follicular Lymphoma International Prognostic Index; LDH = lactate dehydrogenase; OS = overall survival.Solal-Céligny et al, 2004.

Overall Survival According to FLIPI: Clinical Prognostic Factors

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 = watch and wait.Ardeshna et al, 2003.

WW vs. Clb in Advanced Stage Asymptomatic Untreated FL

Ardeshna et al, 2014.

Rituximab vs. WW as Initial Treatment for Asymptomatic FL

Criteria for High Tumor Burden FL

Maximum diameter >7 cm >3 sites with a diameter of >3 cm Systemic symptoms “Substantial” spleen involvement Serious effusions Risk of local compression symptoms Circulating lymphoma cells Peripheral blood cytopenias

Brice et al, 1997.

Impact of Rituximab on OS in Frontline Follicular NHL

Hiddemann et al, 2005.

Herold et al, 2007.

Marcus et al, 2008.

Federico et al, 2013.

FOLLO5: Time to Treatment Failure and Progression-Free Survival

100

80

60

40

20

0 6 12 18 24 30 36 42 48 54 60

100

80

60

40

20

0 6 12 18 24 30 36 42 48 54 60

Trea

tmen

t Fai

lure

(%)

Time (months)

Prog

ress

ion-

Free

Surv

ival

(%)

Time (months)

A B

R-CVPR-CHOPR-FM

R-CVPR-CHOPR-FM

No. at riskR-CVPR-CHOPR-FM

168165171

136147150

119137139

95120120

748395

516668

364750

233232

131920

51212

154

No. at riskR-CVPR-CHOPR-FM

168165171

154157163

136147151

108128130

8589

101

607073

415155

273636

142223

61414

165

Federico et al, 2013.

FOLL05: Grade 3/4 Toxicities by Arm

0.6 3.1 4.2

28.0

49.7

63.7

0.03.1

7.72.5 3.1 4.8

0

20

40

60

Per

cent

age

Anemia Neutropenia Thrombocytopenia Infections

R-CVP R-CHOP R-FM

Anemia P=0.089Neutropenia P<0.001Thrombocytopenia P<0.001Infections P=0.527

2.4 4.7

Nasoupil et al, 2015.

Overall Survival in FL: Lymphocare Data

Rummel et al, 2013.

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

*Up to eight cycles at investigator discretion.Finn et al, 2014.

BRIGHT Study Design

aR-CHOP, n=22.IRC = independent review committee; iNHL = indolent NHL; CR = complete response; PR = partial response.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)

MCL 17/34 (50) 9/33 (27)a 32/34 (94) 28/33 (85)a

aP<0.0001. AEs = adverse events.Finn et al, 2014.

BRIGHT: Grade ≥3 Adverse Events Grade ≥3 AEs (occurring in ≥3% of patients), n (%)

Preselected for R-CHOPPreselected for R-CVP

(n=116 )BR (n=103) R-CHOP (n=98) BR (n=118 )

Hematologic

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

Hemoglobin 0 3 (3) 6 (5) 6 (5)

Platelet count 10 (1) 12 (12) 6 (5) 2 (2)

Non-hematologic

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)

Infection 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)

PRIMA Study Design

CRu = Complete response unconfirmed; PD = progressive disease; SD = stable disease.Salles et al, 2013.

PD/SDoff study

Rituximab maintenance375 mg/m2

every 8 weeks for 2 years

Observation

CR/CRuPR

Random 1:1

Immunochemotherapy8 x rituximab

+8 x CVP or

6 x CHOP or6 x FCM

High tumor burden

untreated follicular lymphoma

INDUCTION MAINTENANCE

5 YEARS FOLLOW-UP

Registration

R = Rituximab.Salles et al, 2013.

PRIMA 6-Year Follow-Up:2-Year R Maintenance Shows Benefit

Overall Survival by Maintenance

Martinelli et al, 2010.Hochster et al, 2009.

Ardeshna et al, 2010. Salles et al, 2011.

RESORT Study Design

Rituximabretreatment atprogressiona

375 mg/m2 qw 4

RANDOMIZE

Rituximab375 mg/m2 qw

4CR or PR

RituximabMaintenancea

375 mg/m2 q 3 months

aContinue 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.

Kahl et al, 2014.

RESORT: Time to Treatment Failure

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

Response per NCI Cheson 1999

criteria

Previously untreated FL (N=154)• Histologically

confirmed FL grades 1, 2, and 3A

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

aTreatment 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.

Frontline R2 vs. R in FL (SAKK 35/10): Overall Response Rate

Rituxim

ab_x0

00d_(n

= 77

)

R2_x0

00d_(n

= 77

)

Rituxim

ab_x

000d

_(n =

77)

R2_x000

d_(n =

77)

0%10%20%30%40%50%60%70%80%90%

100%

10% 13%25%

36%35%

62% 36%

45%

PRCR/CRu

Patie

nts

( %)

Week 10P<0.0001

Week 23P=0.002

45%

75%

61%

81%

Kimby et al, 2014.

SAKK 35/10: Safety

Adverse Events (>1 patient), n (%)

Rituximab (n=76) R2 (n=77)

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.

PET = positron emission tomography.Martin et al, 2014.

CALGB 50803: R2 in Previously Untreated FL

OverallN=55

FLIPI 0-1n=16

FLIPI 2n=35

FLIPI 3n=2

FLIPI Unknown

n=2ORR 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.

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.

Martin et al, 2014.

CALGB 50803: Progression-Free Survival

Years from Study Entry

Pro

ba

bili

ty

0.0 0.5 1.0 1.5 2.0 2.5 3.0

0.0

0.2

0.4

0.6

0.8CALGB 50803

Progression-Free Survival

Unmet Needs in Frontline FL

PET positive after induction Early relapses How to integrate novel agents Surrogate end points

Casulo et al, 2013.

20% of Patients With FL Experience Disease Progression Within 24 Months of Chemoimmunotherapy

Press et al (2013). SWOG S0016. J Clin Oncol.

60

R-CHOP

100

80

60

40

20

024 30 36 42 48 540 6 12 18Time (months)

Pro

gres

sion

-Fre

e S

urvi

val (

%)

1.0E

vent

-Fre

e R

ate

Salles et al (2011). PRIMA Lancet.

Rituximab maintenance0.8

0.6

0.4

0.2

0.00 6 12 18 24 30 36 42 48 54 60

Time (months)

Pro

babi

lity

1.0

0.8

0.6

0.4

0.2

0.0

Rummel el al (2013). Lancet.

B-R

R-CHOP

Time (months)0 6 12 18 24 30 36 42 48 54 60

This suggests a high-risk group of patients who will relapse

early despite different treatment approaches including

maintenance.

aX2.ECOG PS = Eastern Cooperative Oncology Group performance status.Casulo et al, 2013.

Distribution of Characteristics by Group

Characteristic Early

ProgressorReference

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

CI = confidence interval.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)

2-year OS (95% CI) was 71% (61.5-78.0) 5-year OS (95% CI) was 50% (40.3-58.8)

1.0

0 1 2 3 4 5 6 7 8 9 100.0

0.2

0.4

0.6

0.8

Patients at risk:101 78 69 58 49 45 33 14 6 0

Time (years)

Sur

viva

l pro

babi

lity

122

Early Progressor

420 420 407 387 363 344 252 144 33 0420Reference Early

Reference Group

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

Tychyj-Pinel et al (2014). EJNMMI.FOLL05: 202 Patients 2005-2010 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

CT = computed tomography.Trotman et al, 2014.

PFS According to CT ResponseSD/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

Both PET Cut-Offs Predictive of PFSScore ≥3 Score ≥4

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)

63%

23%

Trotman et al, 2014.

Postinduction PET Status (Cut-Off ≥4) and Overall Survival

87%

97%

HR 6.7, 95% CI 2.4-18.5, P=0.0002Median OS: 79 months vs. NR

Trotman et al, 2014.

MRD Predicts Progression-Free Survival in FL

DNA from BM from 415 pts from FOLLO-5Assessed for BCL2/IGH at diagnosis,

posttreatment, and at 12 and 24 monthsMarker detected in 53% pretreatmentThose 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 30-60 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 three prior chemotherapy regimens 34% refractory to last chemotherapy

Cheson et al, 2009.

US Bendamustine Trials: Response in Rituximab-Refractory Patients Patient Group

(N=161)

OverallFLIPI - Low

Int High

Alkylating agentSensitive

RefractoryPurine analog

SensitiveRefractory

CR/CRu (%)

23 17 28 27

28 12

25 20

ORR (%)

76 77 75 79

88 59

81 60

Cheson et al, 2010.

Bendamustine-R in Relapsed iNHL: % Response Rate by Histology

ResponseCategory

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 0Robinson et al, 2008.

Bendamustine-R in Relapsed iNHL: Progression-Free Survival

Cheson et al, 2010.

New Targeted AgentsAgent TargetDaratumumab CD38Polatuzumab vedotin CD79bIbrutinib BtkACP-196 BtkGS-9973 SykIdelalisib PI3-KGS9901 PI3-KIPI-145 PI3-KNivolumab PD-1Pembrolizumab PD-1Pidilizumab PD-1ABT-199 Bcl-2Selinexor XP01 (Nuclear transport)

B-Cell Receptor

Young & Staudt, 2013.

Cell Proliferation, Migration, Growth, Survival

Ibrutinib Monotherapy In Relapsed/Refractory FL (n=40)

Bartlett et al, 2014.

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)

61

101-09: Overall Response Rates by Disease Subgroups

*LPL/WM = lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patient.Gopal et al, 2014.

June 2013Complete Response Stable Disease Progressive Disease Not evaluablePartial Response Minor Response

June 2014

n=2

47%n=59

33%n=41

57%

OverallResponsen=71/125

(95% CI:47.6–65.6)

50%n=63

34%n=42

10%n=12

6%n=7

1%n=1*

2%n=22%

8%n=10

1%n=1*

58%

OverallResponsen=72/125

(95% CI:48.4–66.4)

0% 20% 40% 60% 80% 100%

FLn=72 56% (43–67)

ORR, % (95% CI)

14%n=10

42%n=30

32%n=23

8%n=11

SLLn=28

MZLn=15

LPL/WMn=10

61% (41–79)

47% (21–73)

80% (44–98)

57%n=16

40%n=6

70%n=7

10%n=1

36%n=10

47%n=7

10%n=1

10%n=1

4%n=1

1%n=1

4%n=1

7%n=1

7%n=1

CompleteResponse

StableDisease

ProgressiveDisease

Notevaluable

PartialResponse

M

Overall Response Rate By Disease Subgroups: 2014

Gopal et al, 2014.

101-09: Progression-Free Survival

PFS 2014 (All Patients)* PFS 2014 (By Disease Group)

72 35 18 11 5 128 12 7 4 4 115 6 3 210 7 5 5 3 2

Patients

at risk, n

2014 Median PFS: 11.0 months

*Includes patients who achieved a CR or PR (or MR for LPL/WM) according to IRC assessments

Role of PD-L1 in Antitumor Immune Response

Chen et al, 2012.

Nivolumab in Lymphoma

Leskin et al, 2014

Montoto et al, 2011.

Risk of Transformation in FL

Montoto et al, 2007.

Survival Following Transformation

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 waitb. Rituximab monotherapyc. R-CHOPd. 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-CHOPb. R-ICE with autologous stem cell transplantc. Idelalisibd. 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 therapyb. R-CHOPc. Rituximab/lenalidomided. High-dose therapy with autologous stem cell

transplant

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