indolent non-hodgkin’s lymphoma sharman slides

Jeff P. Sharman, MDMedical DirectorHematology Research US Oncology Eugene, Oregon

Indolent Non-Hodgkin’s Lymphoma

This program is supported by an educational grant from Gilead.

clinicaloptions.com/oncologyIndolent Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia

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Faculty

Program Director:Ian W. Flinn, MD, PhDProgram DirectorDirector, Blood Cancer Research ProgramSarah Cannon Research InstituteNashville, Tennessee

Susan M. O’Brien, MDProfessor of MedicineDepartment of LeukemiaUniversity of Texas M. D. Anderson Cancer CenterHouston, Texas

Jeff P. Sharman, MDMedical DirectorHematology ResearchUS Oncology ResearchEugene, Oregon

Stephan Stilgenbauer, MDAssociate ProfessorDepartment of Internal Medicine II Ulm UniversityUlm, Germany


Faculty Disclosures

Ian W. Flinn, MD, PhD, has disclosed that he has received funds for research support from Celgene, Gilead Sciences, Genentech, Infinity, Janssen Biotech, Millennium, Portola, Seattle Genetics, and Pharmacyclics.

Susan M. O’Brien, MD, has disclosed that she has received consulting fees from Amgen, Celgene, Emergent, Genentech, Gilead Sciences, GlaxoSmithKline, Infinity, Pharmacyclics, and Spectrum; has received funds for research support from Acerta, Emergent, Genentech, Gilead Sciences, Infinity, MorphoSys, Pharmacyclics, Spectrum, and TG Therapeutics; and has served on the advisory board for CLL Global Research Foundation.

Jeffrey P. Sharman, MD, has disclosed that he has received consulting fees from Gilead Sciences and Pharmacyclics and funds for research support from Celgene, Genentech, Gilead Sciences, and Pharmacyclics.

Stephan Stilgenbauer, MD, has disclosed that he has received consulting fees and funds for research support from AbbVie, Amgen, Celgene, Gilead Sciences, GlaxoSmithKline, Janssen Biotech, and Roche.


Initial Treatment by Population for Follicular Lymphoma

Initial Treatment: All Pts (N = 2728)

Clinical trial6.1%

Other1.6% Observation

17.7%Chemotherapy

3.2%

Chemotherapy + rituximab

51.9%

Radiotherapy 5.6%

Rituximabmonotherapy

13.9%

Friedberg JW, et al. J Clin Oncol. 2009;27:1202-1208.


Original GELF Criteria

Any nodal or extranodal tumor mass > 7 cm diameter

≥ 3 nodal sites involved, each with > 3 cm diameter

Presence of any systemic of B symptoms

Splenic enlargement with inferior margin below umbilical line

Compression syndrome (ureteral, orbital, gastrointestinal)

Pleural or peritoneal serous effusion (regardless of cell content)

Leukemia (> 5.0 x 109/L circulating malignant cells)

Cytopenia (< 1.0 x 109/L granulocytes and/or < 100 x 109/L platelets)

Solal-Celigny P, et al. J Clin Oncol. 1998;16:2332-2338.

Low Tumor Burden


Phase III Study: Rituximab vs Watchful Waiting in Asymptomatic FL

Watchful waiting with regular clinic visits(n = 187)

Rituximab 375 mg/m2

wkly for 4 wks(n = 84)

Mo 3

Pts with asymptomatic stage II, III, IV nonbulky FL

(N = 463)

Rituximab 375 mg/m2

wkly for 4 wks(n = 192)

Rituximab 375 mg/m2

every 2 mos

Mo 7CT scan*

Regular clinic visits

Mo 13CT scan if

clinical CR* Mo 25

CT scan*

*If CT shows CR, bone marrow assessed for histology and minimal residual disease.

Continued follow-up

Ardeshna KM, et al. Lancet Oncol. 2014;15:424-435.


Rituximab vs Watchful Waiting in Asymptomatic FL: Remissions, Responses

Radiographically Assessed Spontaneous Remissions and Responses, n/N (%)

7 Mos 13 Mos 25 Mos

Watch and Wait

Overall remission 9/155 (6) 14/145 (10) 15/128 (12)

CR (spontaneous) 3/155 (2) 7/145 (5) 8/128 (6)

PR (spontaneous) 6/155 (4) 7/145 (5) 7/128 (5)

No change 116/155 (75) 94/145 (65) 60/128 (47)

Disease progression 30/155 (19) 37/145 (26) 53/128 (41)

Rituximab Induction

Overall response 62/81 (77) 57/80 (71) 43/75 (57)

CR 29/81 (36) 31/80 (39) 25/75 (33)

CRu 9/81 (11) 8/80 (10) 8/75 (11)

PR 24/81 (30) 18/80 (23) 10/75 (13)

No change 14/81 (17) 12/80 (15) 6/75 (8)


Maintenance Rituximab

Overall response 162/184 (88) 160/180 (89) 144/173 (83)

CR 93/184 (51) 109/180 (61) 119/173 (69)

CRu 16/184 (9) 15/180 (8) 11/173 (6)

PR 53/184 (29) 36/180 (20) 14/173 (8)

No change 16/184 (9) 8/180 (4) 8/173 (5)




Rituximab Maintenance vs Watchful Waiting in Asymptomatic FL: Outcomes


100

75

50

25

00 1 2 3 4 5 6 7

HR: 0.21 (95% CI: 0.14-0.31;log-rank P < .0001)

Pts at Risk, nWatch and wait

Maintenancerituximab

187192

139184

111176

66146

3359

610

11

00

Time to Start of New Treatment

No

Ne

w T

rea

tme

nt

(%)

100

75

50

25

00 1 2 3 4 5 6 7

Pts at Risk, n Watch and wait

Maintenancerituximab

187192

181189

175186

130163

6872

1816

43

00

OS

Yrs From Randomization

100

75

50

25

00 1 2 3 4 5 6 7

187192

121183

92165

54138

2856

69

11

00

PFS

PF

S (

%)

HR: 0.23 (95% CI: 0.16-0.32;log-rank P < .0001)

HR: 0.62 (95% CI: 0.31-1.26;log-rank P = .19)

100

75

50

25

00 1 2 3 4 5 6 7

187192

177187

168182

121158

6469

1515

43

00

Time to Histological Transformation

No

His

tolo

gic

al

Tra

ns

form

ati

on

(%

)HR: 0.73 (95% CI: 0.34-1.54;log-rank P = .40)

OS

(%

)

Yrs From Randomization


Rituximab Induction vs Watchful Waiting in Asymptomatic FL: Quality of Life

Quality of Life at Baseline and Mo 7

Watch and Wait(n = 187)

Maintenance Rituximab (n = 192)

P Value Between Groups

Illness Coping Style

Baseline 159 (70) 171 (72) --

Mo 7 134 (66) 170 (75) .0002

Difference 119 (-5.0) 153 (2.9) .0012

P value baseline vs Mo 7 .0063 .072 --

Illness Impact Bank

Baseline 163 (62) 174 (61) --

Mo 7 137 (67) 175 (71) .095

Difference 125 (4.2) 160 (9.1) .024

P value baseline vs Mo 7 .0089 < .0001 --

Mental Adjustment to Cancer Scale

Baseline 163 (73) 173 (72) --

Mo 7 137 (70) 176 (81) .0004

Difference 125 (-3.2) 160 (8.4) .0004

P value baseline vs Mo 7 .19 .0001 --



Maintenance vs Re-Treatment With Rituximab in Low Tumor Burden FL Randomized phase III trial

of maintenance rituximab vs retreatment with rituximab as needed in pts with previously untreated low tumor burden FL (N = 289)

Primary endpoint: time to treatment failure

Secondary endpoints: time to first cytotoxic therapy, health-related quality of life

Kahl BS, et al. J Clin Oncol. 2014;32:3096-3102.

0 1 2 3 4 5 6 7Yrs Since Random Assignment

Tre

atm

en

t-F

ail

ure

F

ree

Su

rviv

al

(%)

100

80

60

40

20

0

Median FU: 4.5 yrs2-sided log-rank P = .54

Re-treatmentMaintenance

At Risk143146

Failure8078

3 Yrs, %6573

5 Yrs, %5053

0 1 2 3 4 5 6 7Yrs Since Random Assignment

Cy

tox

ic T

he

rap

y-

Fre

e S

urv

iva

l (%

)

80

60

40

20

0

Median FU: 4.2 yrs 2-sided log-rank P = .03


At Risk143146

Cytotoxic288

3 Yrs, %8495

5 Yrs, %8092

100


Maintenance vs Re-Treatment With Rituximab in Low Tumor Burden FL: PFS

Kahl BS, et al. J Clin Oncol. 2014;32:3096-3102.

100

80

60

40

20

0

Pro

gre

ssio

n F

ree

(%)

0 1 2 3 4 5 6 7

Yrs Since First Documented Response

Median FU: 3.8 yrs


At Risk140141

Progression7332

1 Yr, %7690

3 Yrs, %5078


Trial SAKK 35/98: Single-Agent Rituximab at 2 Different Schedules in FL

OS by Treatment Arm

Martinelli G, et al. J Clin Oncol. 2010;29:4480-4484.

EFS by Treatment Arm in Previously Untreated Pts

Responding to Induction Treatment

Yrs

100 1 2 3 4 6 7 8 95

1.0

0.8

0.6

0.4

0.2

0

Pro

bab

ility

ProlongedStandard

P = .045

Yrs

100 1 2 3 4 6 7 8 95

1.0

0.8

0.6

0.4

0.2

0

Pro

bab

ility

ProlongedStandard

P = .0813

High Tumor Burden


Chemo Regimens in Lymphoma

Friedberg JW, et al. J Clin Oncol. 2009;27:1202-1208.

R-CHOP

R-CVPR-Flu

Other55%

23%

16%

6%


Phase III StiL Trial Frontline BR vs R-CHOP in MCL or CD20+ iNHL: Outcomes

PFS FL

Rummel MJ, et al. Lancet. 2013;381:1203-1210.

PFS OS1.0

0.8

0.6

0.4

0.2

00 12 24 36 48 60 72 84 96

Mos

B-RR-CHOP

Median, Mos69.531.2

HR: 0.58 (95% CI: 0.44-0.74;P = .0000148 stratified log-rank)

1.0

0.8

0.6

0.4

0.2

00 12 24 36 48 60 72 84 96

Mos

B-R

R-CHOP

1.0

0.8

0.6

0.4

0.2

00 12 24 36 48 60 72 84 96

Mos

B-RR-CHOP

Median, MosNYR40.9

HR: 0.61 (95% CI: 0.42-0.87; P = .0072)

Pro

bab

ilit

y

Pro

bab

ilit

y

Pro

bab

ilit

y


StiL: Hematologic Adverse Events

Grade 3/4 Events, n (%) R-CHOP Bendamustine + Rituximab

Leukocytopenia 181 (72)* 98 (37)*

Neutropenia 173 (69)* 77 (29)*

Lymphocytopenia 106 (43) 196 (74)

Anemia 12 (5) 8 (3)

Thrombocytopenia 16 (6) 13 (5)


*P < .0001 between groups.


StiL: Nonhematologic Toxic Events

All Grade Events, n (%) Bendamustine + Rituximab (n = 261)

R-CHOP (n = 253)

P Value

Alopecia 0 245 (100)* < .0001

Paresthesia 18 (7) 73 (29) < .0001

Stomatitis 16 (6) 47 (19) < .0001

Skin (erythema) 42 (16) 23 (9) .024

Skin (allergic reaction) 40 (15) 15 (6) .0006

Infectious episodes 96 (37) 127 (50) .0025

Sepsis 1 (< 1) 8 (3) .019


*Includes pts who received ≥ 3 cycles.


Top 5 Regimens for FL From 6/2012 to 6/2014

*1396 pts with FL met the inclusion/exclusion criteria and started LOT1 regimens between 6/2012-6/2014.

Market Connect: McKesson Specialty Health. 2014.

Bendamustine + rituximab (n = 489, 35.0%)

Rituximab (n = 431, 30.9%)

R-CHOP (n = 266, 19.1%)

R-CVP (n = 153, 11.0%)

Other (n = 57, 4.1%)

Follicular Lymphoma LOT1 Top 5 Regimens

35%

31%

19%

11%4%


Response, % StiL[1] BRIGHT[2]

BR(n = 261)*

R-CHOP(n = 253)*

BR(n = 224)

R-CHOP/R-CVP

(n = 223)

ORR 93 91 97 91

CR 40 30 31 25

First-line Bendamustine + Rituximab vs R-CHOP/R-CVP

1. Rummel MJ, et al. Lancet. 2013;381:1203-1210. 2. Flinn IW, et al. Blood. 2014;123:2944-2952.

*Number assessed.


BRIGHT Study: Response Rate by Subtype CR rates with bendamustine + rituximab vs R-CHOP or

R-CVP similar among pts with indolent NHL

CR rate ratio significantly better for bendamustine + rituximab in pts with MCL (P = .018)

Flinn IW, et al. Blood. 2014;123:2944-2952.

Pt Population, n/N (%) CR

BR R-CHOP/R-CVP

Indolent NHL 49/178 (28) 43/174 (25)

Follicular 5/148 (30) 37/149 (25)

Marginal zone 5/25 (20) 4/17 (24)

Lymphoplasmacytic 0/5 1/6 (17)

MCL 17/34 (50) 9/33 (27)*

*R-CHOP, n = 22


Trotman J, et al. Lancet Haematology. 2014;1:e17-e27.

Prognostic Value of PET-CT After 1st Line Therapy in FL

PFS According to PET Scan Score (Cutoff ≥4)

0

20

40

60

80

100

0 12 24 36 48 60 72 84 96

PF

S (

%)

Negative (< 4 points)Positive (≥ 4 points)

PFS at 3 Yrs

100

80

60

40

20

0

Pts

(%

)

74

32

PET-CT negativePET-CT positive

P < .0001


Regimen, % ORR/CR 3-Yr PFS

Bendamustine + rituximab[1] 95/35 65

R-CHOP[1] 91/30 50

Lenalidomide + rituximab[2] 90/65 79

Lenalidomide + Rituximab in Untreated iNHL

1. Rummel MJ, et al. Lancet. 2013;381:1203-1210. 2. Fowler NH, et al. Lancet Oncol. 2014;[Epub ahead of print].


Lenalidomide + Rituximab for Follicular NHL

Response, % Lenalidomide Monotherapy

Lenalidomide + Rituximab

Relapsed/refractory follicular lymphoma[1]

ORR 49 75

CR 13 36

First-line follicular lymphoma[2,3]

OR NA 90-98

CR NA 63-87

1. Leonard J, et al. ASCO 2012. Abstract 8000. 2. Martin P, et a l. Proc ICML 2013. Abstract 063. 3. Fowler NH, et al. Lancet Oncol. 2014;[Epub ahead of print].


Phase III Study of First-line Lenalidomide + Rituximab for Indolent NHL Randomized, open-label phase III study

Treatment-naive pts with CD20-positive iNHL

with at least 1 lesion > 2 cm not previously irradiated;

stage II-IV; ECOG ≤ 2(planned N = 1000)

Lenalidomide + Rituximab(n = 390)

R-CHOP or R-CVP or BR(n = 397)

Primary endpoints: CR/CRu, PFS

Lenalidomide: 20 mg on Days 2-22 q4w x 6; if CR then 10 mg on Days 2-22 q4w x 12; if PR after 6 cycles, continue 20 mg for 3-6 cycles, then 10 mg on Days 2-22 q4w cycles for up to 18 cycles.Rituximab: 375 mg/m2 on Days 1, 8, 15 and 22 of cycle 1, Day 1 of cycles 2-6; 8 wks later responding pts continue q8w x 12.

Clincaltrials.gov. NCT01650701. Fowler NH, et al. Lancet Oncol. 2014;[Epub ahead of print].

Relapsed Disease


Top 5 Regimens for FL From 6/2012 to 6/2014

Market Connect: McKesson Specialty Health. 2014.

*440 pts with FL met the inclusion/exclusion criteria and started LOT2 regimens between 6/2012-6/2014.

Bendamustine + rituximab (n = 190, 43.2%)

Rituximab (n = 129, 29.3%)

Other (n = 75, 17.1%)

RCHOP (n = 25, 5.7%)

Bendamustine (n = 21, 4.8%)

43%

29%

17%

6%5%


ORR, % CR, % PFS, Mos

Rituximab (n = 33)[1] 64 39 14

Radioimmunotherapy (n = 142)[2] 67 50 18

Bendamustine + rituximab (n = 37)[3] 86 35 23

Efficacy Following Rituximab Therapy

1. Tobiani K, et al. Cancer Sci. 2011;102:1698-1705. 2. Leahy MF, et al. Blood. 2011;117:45-52. 3. Robinson KS, et al. J Clin Oncol. 2008;26:4473-4479.

Novel Agents


B-Cell Receptor Signaling Pathway


Phase II Study 101-09: Idelalisib Monotherapy in Refractory iNHL

Gopal A, et al. N Engl J Med. 2014;370:1008-1018.

2 pts had no baseline evaluation

1 pt had disease progression on the basis of lymph node biopsy, no baseline evaluation

FL (n = 72)SLL (n = 28)MZL (n = 15)LPL/WM (n = 10)

75

50

25

0

-25

-50

-75

-100Individual Pts

(N = 125)

SP

D o

f M

easu

red

Lym

oh

No

des

(B

est

% C

han

ge

Fro

m B

asel

ine)


Phase II Study of Idelalisib Monotherapy in Refractory iNHL: PFS and DOR

PFS Duration of Response


100

75

50

25

0

Per

cen

t W

ith

PF

S

Median: 11 mos(N = 125)

Mos From Start of Idelalisib

180 3 6 9 12 15

Pts at Risk, n 125 100 59 39 20 13 0

100

75

50

25

0P

erce

nt

Wit

h C

on

tin

ued

R

esp

on

se

Median: 12.5 mos(N = 71)

Mos From Response

180 3 6 9 12 15

Pts at Risk, n 71 54 34 17 9 0 0


Phase II Study of Idelalisib Monotherapy in Refractory iNHL: Pt DispositionDuration of Idelalisib Therapy, Mos

Median 6.6

Range 0.6-23.9

Treatment Disposition, n (%)

Ongoing 40 (32)

Discontinued 85 (68)

Progressive disease 41 (33)

Adverse event 25 (20)

Death 8 (6)

Investigator request 7 (6)

Withdrew consent 4 (3)



Idelalisib Indications and Usage

Relapsed CLL in combination with rituximab, in pts for whom rituximab monotherapy would be appropriate

Relapsed FL,* in pts with ≥ 2 previous systemic therapies

Relapsed SLL,* in pts with ≥ 2 previous systemic therapies

Idelalisib [package insert].

*Accelerated approval was given based on ORR, with limited evidence regarding pt survival and disease symptoms. Continued approval is contingent upon confirmatory trials and verification of clinical benefit.


Idelalisib Label Black Box Warning

Fatal and/or serious hepatotoxicity occurred in 14% of pts in clinical trials

– Hepatic function should be monitored before and during treatment

– Dose adjustments/discontinuation should be considered when necessary

Fatal and/or serious and severe diarrhea or colitis occurred in 14% of pts in clinical trials

– Pts should be monitored for these symptoms and dose adjustments or discontinuation should be considered when necessary

Fatal and serious pneumonitis and intestinal perforation can occur during treatment

– Dose adjustments or discontinuation should be considered when necessary

Idelalisib [package insert].


Ibrutinib Efficacy in FL Pts

Median DORMedian PFS

10.3 mos13.4 mos

12.3 mos19.6 mos

NENE

55% 56%

25%

Fowler NH, et al. ASH 2014. Abstract 156

0

20

40

60

80

100

1.25 mg/kg/day(n = 4)

≥ 2.5 mg/kg/day (n = 11)

≥ 5.0 mg/kg/day (n = 9)

CR PR

25% 27.3% 33.3%

27.3% 22.2%


Ibrutinib Efficacy in iNHL: Patients’ Time on Study Treatment by Best Response

Advani RH, et al. J Clin Oncol. 2013;31:88-94.

CLL/SLLMCLDLBCLFLOther indolent NHL

Max % Change in Tumor Burden (n = 48)

200

150

100

50

0

-50

-100Ch

an

ge

Fro

m B

as

eli

ne

SP

D (

%)

0 5 10 15 20 25 30

CL

L/S

LL

MC

LF

LD

LB

CL

Oth

er

Ind

ole

nt

NH

L

Mos on Study

DLTDisease progressionOff study, pt/ investigator decisionIntercurrent illness/ adverse eventOn study


Ibrutinib in Relapsed/Refractory FL

Response, n (%) Pts (N = 16)

ORR 6 (38)

CR 3 (19)

PR 3 (19)

Median DOR, mos 12.3

Median time to first response, mos (range) 4.7 (2-12)

Median time to first PR, mos (range) 4.6 (2-11)

Median time to first CR, mos (range) 11.5 (5-12)

Median PFS, mos 13.4

OS No deaths

Advani RH, et al. J Clin Oncol. 2013;31:88-94. Fowler NH, et al. ASH 2014. Abstract 156.


Ibrutinib Indications and Usage

For pts with MCL who have received at least 1 previous therapy*

In CLL pts who have received at least 1 previous therapy

In CLL pts with 17p deletion

Ibrutinib [package insert].

*Accelerated approval received for this specific indication was established on ORR. Improvements in survival or disease-related symptoms have not been proven. Continued approval for this indication is contingent upon clinical benefit being confirmed in ongoing clinical trials.


Ibrutinib Warning and Precautions

Hemorrhage: monitor for bleeding

Infections: monitor for fever and infections

Cytopenias: monitor CBC monthly

Atrial fibrillation

Second primary malignancies: includes skin cancers and other carcinomas

Embryo-fetal toxicity: can cause fetal harm

Ibrutinib [package insert].


Lenalidomide + Rituximab vs Lenalidomide for Relapsed FL Randomized phase II study (N = 89)

Eligibility: relapsed FL with previous rituximab, TTP ≥ 6 mos from last dose

Efficacy Lenalidomide(n = 45)


ORR, % (95% CI) 51 (36-66) 73 (52-85)

CR, % 13 36

PR, % 38 36

Median EFS, yrs 1.2 2.0

2-yr EFS, % 27 44

Leonard J, et al. ASCO 2012. Abstract 8000.

Rituximab


Lenalidomide(n = 45)

Modified study design to exclude rituximab-only armGrade 1-3a relapsed

FL after ≥ 1 rituximab-based

regimen


Polatuzumab Vedotin and Pinatuzumab Vedotin Activity in Rel/Ref NHL

Morschhauser F, et al. ASCO 2014. Abstract 8519.

Antibody With Potential Conjugation Sites for VC-MMAE (*)

VC-MMAE (linker-drug)

MMAEMC VC PABC

Protease cleavage

ADC binds to receptor

ADC-receptor complex is internalizedADC in circulation

Apoptosis (cell death)Cytotoxic agent is released in lysosomes Microtubule

disruption

** ******

*-Cys

SONO O

O

O

NH

HN

NH

OO

NO

NH

ON

OON

OO

NH OH

HN

H2NO

SAR-3419 CD-19 – DM4SGN-CD19a CD19 – MMAF

Pinatuzumab CD22 – MMAEPolatuzumab CD79 – MMAE


CD79b and CD22 Activity in Relapsed/ Refractory NHL: Study Design

Relapsed/refractory FL = 41

Relapsed/refractory DLBCL = 81

Rituximab + CD22 ADC

Rituximab + CD79b ADC

Rituximab 375 mg/m2 + ADC 2.4 mg/kg administered in every-21-day cycles up to 1 yr


Biopsy at progression


Phase II Polatuzumab vs Pinatuzumab: Tumor Response and Survival in FL Pts


1.0

0.8

0.6

0.4

0.2

00 2 4 6 8 10 12 14

Mos

Su

rviv

al P

rob

abil

ity

CD22 + RCD79b + R

Median PFS for FL not reported due to

insufficient duration of follow-up

Pinatuzumab (Anti-CD22 ADC) + R Polatuzumab (Anti-CD22 ADC) + R

Rituximab-containing regimen Non-rituximab–containing regimen Not refractory

100

50

0

-50

-100

100

50

0

-50

-100Max

% C

han

ge

Tu

mo

r D

ecre

ase

Fro

m B

ase

lin

e


Polatuzumab (CD79b) + R vs Pinatuzumab (CD22) + R: TEAEs


FatigueDiarrhea

Peripheral neuropathyNausea

NeutropeniaConstipation

Peripheral sensory neuropathyDecreased appetite

AstheniaPyrexia

VomitingCough

InsomniaDyspnea

Abdominal painArthralgia

AnemiaAlopecia

Pain in extremetyHeadacheBack painDizziness

Peripheral edemaMyalgia

Decresed weightDyspepsia

30 20 10 0 0 10 20 30Frequency (%) Frequency (%)

CD22 + R CD79b + RA

E P

refe

rre

d T

erm

1

2

3

4

Grade


Summary

Agent ORR, % CR, % PFS, Mos Comment

Idelalisib[1] 57 6 11 Good study

Ibrutinib[2] 38 19 14 Phase 1, small study

Lenalidomide + rituximab[3]

73 36 24 Suboptimal rituximab

CD79-ADC[4] 70 40 N.R. Neuropathy

1. Gopal A, et al. N Engl J Med. 2014;370:1008-1018. 2. Advani RH, et al. J Clin Oncol. 2013;31:88-94. 3. Leonard J, et al. ASCO 2012. Abstract 8000. 4. Morschhauser F, et al. ASCO 2014. Abstract 8519.


Phase III RELEVANCE Study: Len/R vs R-Chemo in Untreated FL

Treatment arms

– R + chemo: Investigator’s choice of R-CHOP, R-CVP, BR for 6-8 cycles

– R2: R + lenalidomide 20 mg for 6 cycles, and then 10 mg if CR

Morschhauser F, et al. ICML 2013. Abstract 136. ClinicalTrials.gov. NCT01650701.

First-line FL(N = 1000

Planned enrollment)

R2 Arm R2 Maintenance

R + Chemo Rituximab maintenance


Conclusions

In frontline management of indolent lymphoma, management currently stratified based on disease bulk

Several recent data sets shed light on use of rituximab monotherapy in low tumor burden indolent lymphoma

In high tumor burden indolent lymphoma, BR has displaced R-CHOP and other frontline treatment options

Lenalidomide and rituximab may be next paradigm change in frontline indolent NHL

Standards in relapsed disease far from standardized

Multiple new agents with novel mechanisms of action promise to bring more change in this space soon

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Additional CME-certified slidesets with expert faculty commentary on all the key studies

Downloadable slidesets for self-study or use in your own presentations

clinicaloptions.com/oncology

http://www.clinicaloptions.com/oncology

indolent non-hodgkin’s lymphoma sharman slides

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