Cco clin onc_june _2012_lymphoma_slides

June 1-5, 2012
Chicago, Illinois
Lymphoma
CCO Independent Conference Highlights
of the 2012 American Society of Clinical Oncology Annual Meeting*
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Lymphomas
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Lymphomas
Outline
 StiL NHL 1-2003: updated results of B-R vs CHOP-R for MCL and indolent lymphomas
 CALGB 50401: lenalidomide ± rituximab for relapsed FL following prior rituximab-based
therapy
 CALGB 50102/SWOG S0016: exploratory subset analysis of CHOP-R vs CHOP-RIT as
frontline therapy for FL
 FOLL05: CHOP-R vs CVP-R vs FM-R for frontline treatment of active advanced-stage
FL
 Population-based study of FL transformation in the era of immunochemotherapy
 EORTC 20012: first results for dose-escalated BEACOPP vs conventional ABVD in
advanced-stage Hodgkin’s lymphoma
 Ongoing phase II study of retreatment with brentuximab vedotin in CD30-positive
Hodgkin’s lymphoma or ALCL
 RICOVER-60: rituximab underdosing in subpopulations of elderly DLBCL patients
 LNH 03-6B GELA: final analysis of CHOP-R-14 compared with CHOP-R-21 in elderly
DLBCL patients

Lymphomas
StiL NHL 1-2003: Study Design
 Updated results of randomized, open-label phase III trial
– Median follow-up: 45 mos
Rummel M, et al. ASCO 2012. Abstract 3.
B-R: bendamustine 90 mg/m2
on Days 1-2; rituximab 375 mg/m2
on Day 1; 4-wk cycles for 6 cycles max
CHOP-R: cyclophosphamide 750 mg/m2
on Day 1; doxorubicin 50 mg/m2
on Day 1; vincristine 1.4
mg/m2
on Day 1; prednisone 100 mg on Days 1-5; rituximab 375 mg/m2
on Day 1; 3-wk cycles for 6
cycles max
Treatment-naive
patients with
MCL or indolent
CD20-positive
lymphoma
(N = 549)
B-R
(n = 261)
CHOP-R
(n = 253)
 Primary endpoint: noninferiority of B-R vs CHOP-R for PFS (decrease < 10% at 3 yrs)
 Secondary endpoints: response rate, time to next treatment, EFS, OS, adverse events, stem cell
mobilization capacity (younger patients)

Lymphomas
StiL NHL 1-2003: PFS
 Superior median PFS with B-R vs CHOP-R in overall population
– 69.5 vs 31.2 mos (HR: 0.58; 95% CI: 0.44-0.74; P = .0000148)
 B-R superiority maintained across several patient subgroups
Patient
Subgroup
HR*
(95% CI)
P Value
FL
FLIPI 0-2
FLIPI 3-5
0.61 (0.42-0.87)
0.56 (0.31-0.98)
0.63 (0.38-1.04)
.0072
.0428
.0679
MCL 0.50 (0.29-0.81) .0061
MZL 0.70 (0.34-1.43) .3249
Waldenströms 0.33 (0.11-0.64) .0033
*HR < 1 favors B-R vs CHOP-R.
Patient
Subgroup
HR*
(95% CI)
P Value
LDH, IU/L
≤ 240
> 240
0.48 (0.34-0.67)
0.74 (0.49-1.08)
< .0001
.1182
Age, yrs
≤ 60
> 60
0.52 (0.33-0.79)
0.62 (0.45-0.84)
.0022
.0022

Lymphomas
StiL NHL 1-2003: Response and OS
 Similar ORR with B-R vs CHOP-R: 92.7% vs 91.3%
– Higher CR with B-R: 39.8% vs 30.0% (P = .021)
 No difference in OS over long-term follow-up
– Possibly due to indolent disease and use of various salvage
therapies
0
60
70
80
90
OSRate(%)
2 3 4 5
Follow-Up (Yrs)
6 7
50
B-R
CHOP-R

Lymphomas
StiL NHL 1-2003: Toxicity
 More favorable overall toxicity profile with B-R vs CHOP-R
– Similar incidence of secondary malignancies (20 vs 23 cases)
Selected Adverse Events, % B-R
(n = 261)
CHOP-R
(n = 253)
P Value
Grade 3/4 hematologic toxicities
Lymphocytopenia
Leukocytopenia
Neutropenia
Thrombocytopenia
Anemia
74
37
29
5
3
43
72
69
6
5
All-grade nonhematologic toxicities
Infectious complications
Skin (erythema)
Allergic skin reaction
Paresthesias
Stomatitis
Sepsis
36.8
16.1
15.3
6.9
6.1
0.4
50.2
9.1
5.9
28.9
18.6
3.2
.0025
.0122
.0003
< .0001
< .0001
.0190

Lymphomas
StiL NHL 1-2003: Expert Perspectives
 Updated analysis continues to demonstrate B-R is a
reasonable option for frontline treatment of FL and MCL
patients
 B-R regimen associated with lower rates of toxicity vs
CHOP-R
 Await final publication before frontline B-R regimen can be
considered “state of the art”

Lymphomas
CALGB 50401: Study Design
 Randomized phase II trial
– Median follow-up: 1.7 yrs (range: 0.1-4.1)
Leonard J, et al. ASCO 2012. Abstract 8000.
Rituximab: 375 mg/m2
on Days 8, 15, 22, 29 of cycle 1
Lenalidomide: 15 mg cycle 1, then 20-25 mg cycles 2-12 on Days 1-21; dose escalated as tolerated
Aspirin or anticoagulation prophylaxis given to patients at high risk for deep vein or arterial thrombosis
Patients with FL who
relapsed following
≥ 1 rituximab-based
regimen
(N = 89)
Rituximab + Lenalidomide
(n = 44)
Lenalidomide
(n = 45)
 Primary endpoint: ORR (≥ 35% ORR considered of statistical interest)
 Secondary endpoints: CR rate; EFS; toxicity; immunologic correlates; identify benchmarks for future
studies
12 x 28-day cycles

Lymphomas
CALGB 50401: Response and EFS
 Lenalidomide active both as monotherapy and combined
with rituximab
– Outcomes improved with combination
Leonard J, et al. ASCO 2012. Abstract 8000. Reproduced with permission.
Efficacy Outcome Lenalidomide + Rituximab
(n = 44)
Lenalidomide
(n = 45)
ORR, %
CR
PR
72.7
36.4
36.4
51.1
13.3
37.8
EFS
Median EFS, yrs
2-yr EFS, %
2.0*
44
1.2
27
 Unadjusted HR
 Adjusted HR†
2.1 (P = .010)
1.9 (P = .061)
*P = .008
†
Adjusted for FLIPI risk category, to show difference in EFS not due to baseline differences.

Lymphomas
CALGB 50401: Toxicity
 Hematologic toxicities primary grade 3/4 adverse events
 Similar incidence of thrombosis events between treatment
arms
– 2 vs 7 cases in combination vs monotherapy arms (P = .158)
Leonard J, et al. ASCO 2012. Abstract 8000. Reproduced with permission.
Grade 3/4 Adverse Event, % Lenalidomide + Rituximab
(n = 44)
Lenalidomide
(n = 45)
Hematologic toxicities
Neutropenia
Thrombocytopenia
19
10
16
0
Nonhematologic toxicities
Fatigue
Rash
Thrombosis
Infection
14
8
4
0
9
4
16
4

Lymphomas
CALGB 50401: Expert Perspectives
 Lenalidomide active in relapsed (nonrefractory) FL
– Efficacy outcomes (response and EFS) improved with
combination of lenalidomide plus rituximab vs lenalidomide
monotherapy
 Comparison with rituximab alone not possible
– Study arm terminated early
 Lenalidomide plus rituximab combination currently under
investigation for both maintenance and upfront strategies
in FL
Leonard J, et al. ASCO 2012. Abstract 8000.

Lymphomas
SWOG S0016/CALGB 50102: Study Design
 Exploratory analysis of randomized phase III trial[1]
– Excellent PFS, OS associated with both regimens[2]
1. Press OW, et al. ASCO 2012. Abstract 8001. 2. Press O, et al. ASH 2011. Abstract 98.
on Day 1; vincristine
1.4 mg/m2
on Days 1, 6, 48, 90, 134,
and 141
CHOP-RIT: cyclophosphamide 750 mg/m2
1.4 mg/m2
on Days 1, 6, 48, 90,
134, and 141; followed by dosimetric infusion of tositumomab/131
I-tositumomab followed 1 wk later by
131
I-tositumomab to a total dose of 75 cGY
Patients with
untreated advanced
FL (bulky stage II-IV)
(N = 554)
CHOP-R
(n = 279)
CHOP
(n = 275)
RIT
6 cycles
Stratified by β2-M level (elevated vs not elevated)
2 wks

Lymphomas
SWOG S0016/CALGB 50102: Predictive
Factors for PFS Interaction With
Treatment
 β2-M level only baseline factor significantly predictive of PFS
interaction with treatment arm in univariate analysis
 No baseline factors significantly predictive of OS interaction
Press OW, et al. ASCO 2012. Abstract 8001.
Baseline Factors Significantly
Associated With Improved PFS
Univariate HR
(95% CI)
P Value P Value for PFS
Interaction With
Treatment Arm
Low hemoglobin (< 12 g/dL) 2.14 (1.46-3.16) < .0001 .39
Maximal lymph node size ≥ 6 cm 1.95 (1.47-2.59) < .0001 .20
PS ≥ 1 1.72 (1.27-2.34) .0004 .93
Elevated β2-M 1.69 (1.26-2.27) .0004 .02
Elevated LDH 1.60 (1.17-2.18) .003 .59
> 4 lymph nodes 1.52 (1.14-2.02) .004 .75
Disease stage (II/III vs IV) 1.42 (1.05-1.93) .02 .19

Lymphomas
Value of FLIPI and FLIPI-2 Models
 Both FLIPI and FLIPI-2 models predictive of PFS and OS in
univariate analysis
0
10
20
30
40
50
60
70
80
90
100
FLIPI FLIPI-2
Risk Group Models
5-YrPFS(%)
Low
Intermediate
High
0
10
20
30
40
50
60
70
80
90
100
FLIPI FLIPI-2
Risk Group Models
5-YrOS(%)

Lymphomas
Value of Lab-Based Risk Model
 Lab-based risk model developed using β2-M and LDH levels
– Optimal threshold values determined by Wald Chi square statistics
– Best cutpoint: ~ 150% of IULN for both
– Next best cutpoint: ~ 90% of IULN for both
 5-yr PFS for lab-based
risk model using 150%
of IULN
– Low: 67%
– Intermediate: 56%
– High: 20%
 5-yr OS for lab-based
risk model using 150%
of IULN
– Low: 93%
– Intermediate: 78%
– High: 58%

Lymphomas
SWOG S0016/CALGB 50102: Risk Models
Predictive for Treatment Interaction
 Only lab-based model significant for PFS interaction with
treatment arm
Risk Models Significantly
Associated With PFS and OS
Univariate HR
(95% CI)
P Value P Value for
Interaction With
Treatment Arm
PFS
FLIPI
FLIPI-2
Lab based (150% cut point)
1.55 (1.27-1.88)
1.90 (1.49-2.41)
2.00 (1.59-2.53)
1.79 (1.47-2.18)
< .0001
< .0001
< .0001
< .0001
,08
.11
.03
.07
OS
FLIPI
FLIPI-2
1.95 (1.38-2.73)
2.65 (1.72-4.07)
2.61 (1.81-3.75)
2.24 (1.57-3.21)
.0001
< .0001
< .0001
< .0001
.27
.11
.08
.46

Lymphomas
SWOG S0016/CALGB 50102: Treatment
Outcome by Patient Subgroup
 Patient subgroups defined by β2-M levels and lab-based risk
categories may experience different outcomes to treatment
5-Yr PFS Rate, % CHOP-R
(n = 279)
CHOP-RIT
(n = 275)
P Value for
Interaction
β2-M levels
Normal
Elevated
61
59
76
57
.02
Lab-based risk model*
Low
Intermediate
High
63
54
30
70
58
10
.03
*Using 150% of IULN.

Lymphomas
SWOG S0016/CALGB 50102: Expert
Perspectives
 Similar outcomes achieved with CHOP-R vs CHOP-RIT in
previously untreated FL
 Factors found to be significant for PFS interaction with
treatment arm
– β2-M
– Lab-based risk model
 Patient subgroups defined by β2-M levels and lab-based
risk categories may experience different outcomes to
treatment

Lymphomas
FOLL05: Study Design
 Randomized phase III trial
– Median follow-up: 34 mos (range: 1-70)
Federico M, et al. ASCO 2012. Abstract 8006.
CVP-R: cyclophosphamide 750 mg/m2
on Day 1; vincristine 1.4 mg/m2
on Day 1; prednisone 40 mg/m2
on Day 1
on Day 1; vincristine 1.4 mg/m2
on Day 1; prednisone 100 mg/m2
on Day 1
FM-R: fludarabine 25 mg/m2
on Days 1-3; mitoxantrone 10 mg/m2
on Day 1; rituximab 375 mg/m2
on Day 1
 Primary endpoint: TTF from registration date
Patients with previously
untreated, active
stage II-IV FL
(N = 504)
CVP-R
(n = 168)
CHOP-R
(n = 165)
3 x 21-day cycles
FM-R
(n = 171)
CVP-R for
additional 5 cycles
CHOP-R for
additional 3 cycles*
FM-R for
additional 3 cycles*
≥ PRStratified by FLIPI score
(0-2 vs 3-5)
*Followed by 2 cycles of
rituximab.

Lymphomas
FOLL05: TTF and PFS
 Improved 3-yr TTF and PFS with CHOP-R and FM-R vs CVP-R
 Significant superiority of CHOP-R or FM-R vs CVP-R
– Consistent across all patient subgroups tested
Efficacy Outcome, % CVP-R
(n = 168)
CHOP-R
(n = 165)
FM-R
(n = 171)
3-yr TTF 45 63 59
3-yr PFS 52 68 63
Comparison TTF PFS
HR (95% CI) P Value* HR (95% CI) P Value
CHOP-R vs CVP-R 0.60 (0.43-0.83) .007 0.61 (0.43-0.87) .006
FM-R vs CVP-R 0.64 (0.46-0.88) .020 0.67 (0.47-0.94) .022
CHOP-R vs FM-R 0.94 (0.66-1.33) .971 0.91 (0.63-1.33) .628
*Adjusted.

Lymphomas
FOLL05: Response
0
10
20
30
40
50
60
70
80
90
ResponseRate(%)
OR CR PR SD, PD, or EW
Depth of Response
100
88
93 91 91
67
72 72
70
21 21 19 20
886
11
CVP-R
CHOP-R
FM-R
Overall

Lymphomas
FOLL05: Toxicity
 Grade 3/4 adverse events highest in FM-R arm
– Neutropenia (most frequent) increased with treatment duration
 Progressive disease most frequent cause of death on-study
 Secondary malignancies reported in all treatment arms
– Highest rate in FM-R arm (P = .030)
Grade 3/4 Adverse
Event, %
CVP-R
(n = 168)
CHOP-R
(n = 165)
FM-R
(n = 171)
Neutropenia* 27.7 50.0 63.5
Thrombocytopenia* 0 3.0 7.6
Anemia 0.6 3.0 4.1
Infections 2.4 3.0 4.7
*P < .001

Lymphomas
FOLL05[1]
: Expert Perspectives
 3-yr PFS rate similar to observation arm and lower than
rituximab maintenance arm in PRIMA study (rituximab
maintenance for 2 yrs vs observation only after response
to rituximab plus chemotherapy)[2]
– PRIMA rituximab maintenance arm: 74.9%
– PRIMA observation arm: 57.6%
– FOLL05: 58.9%
 CHOP-R remains a standard therapy for induction
treatment of patients with FL
1. Federico M, et al. ASCO 2012. Abstract 8006. 2. Salles G, et al. Lancet. 2011;377:42-51.

Lymphomas
Impact of Immunochemotherapy on FL
Transformation: Study Design
 Retrospective population-based study to determine impact of
immunochemotherapy on risk of FL transformation to aggressive
lymphoma
 Patients with FL identified from British Columbia Cancer Agency
Lymphoid Cancer Database (N = 261)
– Advanced stage (III/IV, B symptoms or bulky disease ≥ 10 cm),
grades 1-3A
– Symptomatic at diagnosis requiring systemic therapy
– Previous anthracycline-based regimen not permitted
 Transformation diagnosed by biopsy confirmation or predefined
clinical assessment (rapid nodal growth, increased LDH, new
hypercalcemia, extensive involvement of new extranodal sites)
Al-Tourah AJ, et al. ASCO 2012. Abstract 8049.

Lymphomas
Transformation: Initial FL Treatment
 CVP-R and CVP-R followed by maintenance R most common initial therapy
regimens
– CVP-R followed by rituximab maintenance: 55%
– CVP-R: 38%
– Fludarabine-R: 4%
– Fludarabine-R followed by R maintenance: 0.8%
– Bendamustine-R followed by R maintenance: 0.8%
– CPF-R: 0.8%
– Chlorambucil-R: 0.4%
– Chlorambucil-R followed by R maintenance: 0.4%
– FCR followed by R maintenance: 0.4%
Al-Tourah AJ, et al. ASCO 2012. Abstract 8049.

Lymphomas
Transformation: Incidence & Prognosis[1]
 Overall risk of transformation
– ~ 2% per yr
– 10% at 5 yrs (vs 20% in pre-rituximab era[2]
)
 Lower transformation risk with use of maintenance rituximab
(n = 151) compared with chemotherapy-rituximab at induction
only (n = 110)
– 8% vs 20% at 5 yrs (P = .003)
 Poor prognosis after transformation regardless of use of
immunochemotherapy
– Median posttransformation OS: 6 mos
1. Al-Tourah AJ, et al. ASCO 2012. Abstract 8049. 2. Montoto S, et al. J Clin Oncol. 2011;29:1827-1834.

Lymphomas
EORTC 20012: Study Design
 First results of randomized phase III trial
Carde PP, et al. ASCO 2012. Abstract 8002.
ABVD: 56-day cycles of doxorubicin 25 mg/m2
on Days 29, 43; bleomycin 10 mg/m2
on Days 29, 43;
vinblastine 6 mg/m2
on Days 29, 43; dacarbazine 375 mg/m2
on Days 29, 43
Dose-escalated BEACOPP: 21-day cycles of bleomycin 10 mg/m2
on Day 8; etoposide 200 mg/m2
on
Days 1-3; doxorubicin 35 mg/m2
on Day 1; cyclophosphamide 1200 mg/m2
1.4 mg/m2
on Day 8; procarbazine 100 mg/m2
on Days 1-7; prednisone 40 mg/m2
on Days 1-14
BEACOPP: 21-day cycles of bleomycin 10 mg/m2
on Day 8; etoposide 100 mg/m2
on Days 1-3;
doxorubicin 25 mg/m2
on Day 1; cyclophosphamide 650 mg/m2
1.4 mg/m2
on Day 8; procarbazine 100 mg/m2
on Days 1-7; prednisone 40 mg/m2
on Days 1-14
Patients with
previously untreated,
poor-risk,
stage III/IV
Hodgkin’s lymphoma
(N = 549)
ABVD
(n = 275)
BEACOPP
dose-escalated
(n = 274)
 Primary endpoint: EFS from time of randomization
BEACOPP
baseline
BEACOPP
baseline
ABVD ABVD
4 cycles 2 cycles 2 cycles
Stratified by institution and IPS (3 vs ≥ 4)
If PR
≥ 50%
If PR
≥ 75%
or CRu

Lymphomas
EORTC 20012: Survival Outcomes
 Similar 4-yr EFS and OS with ABVD vs BEACOPP
– Superior PFS with BEACOPP (not a defined study endpoint)
 First EFS events well distributed among treatment arms
– Early discontinuation, no CR/CR after 8 cycles, disease
progression or relapse, or death
4-Yr Survival
Outcome, %
ABVD
(n = 275)
BEACOPP
(n = 274)
HR
(95% CI)
P Value
EFS 63.7 69.3
0.86
(0.64-1.15)
.313
PFS 69.4 84.0
0.50
(0.34-0.73)
.0003
OS 86.7 90.3
0.71
(0.42-1.21)
.208

Lymphomas
EORTC 20012: Response and Mortality
Incidence
 CR/CRu incidence similar with ABVD vs BEACOPP
– Sensitivity analysis: 82.5% vs 82.8%
– Primary analysis: 73.5% vs 69.0%
 No significant difference in 4-yr cumulative incidence of deaths
between ABVD and BEACOPP arms
 Incidence rates for different causes of death generally similar
between treatment arms
– ≈ 25% to 30% of deaths occurred ≤ 3 mos after treatment
 Similar cumulative 4-yr incidence of secondary malignancies in
ABVD and BEACOPP arms: 3.4% vs 4.7% (Gray test P = .584)

Lymphomas
EORTC 20012: Expert Perspectives
 BEACOPP offered no efficacy advantage over ABVD
– No difference in OS
 ABVD remains acceptable therapeutic regimen for
treatment of high-risk patients with advanced-stage
Hodgkin’s lymphoma

Lymphomas
Phase II Brentuximab Vedotin Retreatment
Trial: Study Design
 Ongoing phase II trial (N = 24)
– Enrolled patients achieved CR/PR with brentuximab vedotin in
previous pivotal phase II trial
– Treatment discontinued during remission
– Enrollment in current study following disease progression/relapse
 Treatment: 1.2 or 1.8 mg/kg brentuximab vedotin every 21 days
– No maximum number of cycles
 Median time between previous brentuximab vedotin treatment
and current retreatment
– 7.7 mos (range: 1-44)
Bartlett N, et al. ASCO 2012. Abstract 8027.

Lymphomas
Trial: Response
 Durable responses associated with brentuximab vedotin
retreatment
Response Outcome Brentuximab Vedotin Retreatment (N = 23*)
Overall
(n = 23)
Hodgkin’s Lymphoma
(n = 15)
Systemic ALCL
(n = 8)
OR, %
CR
PR
70
39
30
60
20
40
88
75
13
SD, % 9 13 0
PD, % 22 27 13
Median DOR, mos (range)
Median DOR after CR
8.8 (0-28+)
8.8 (0-28+)
Median PFS after
retreatment, mos
12.9
*1 patient not evaluable for response.

Lymphomas
Trial: Toxicity
 Median duration of retreatment: 6.5 mos (range: 1.3-28.6)
 Most frequent grade 3/4 adverse events during
retreatment
– Anemia, fatigue, nausea, arthralgia, back pain, dyspnea
 46% incidence of peripheral sensory neuropathy
– All cases grade 1 or 2
– 50% experienced improvement or resolution of symptoms
during retreatment
– 54% of patients had existing peripheral neuropathy at
baseline prior to retreatment
– 31% experienced worsening of symptoms during retreatment

Lymphomas
Trial: Expert Perspectives
 Brentuximab vedotin is an important advance in the
treatment of patients with CD30-positive lymphomas
 Current study demonstrates efficacy of retreatment with
brentuximab vedotin
– Similar to other antibody-based therapies, many of which
can also be administered multiple times (eg, rituximab)

Lymphomas
Elderly Subpopulations of RICOVER-60:
Study Rationale
 Little pharmacokinetic data available for rituximab in
DLBCL
– Dosing of rituximab with CHOP based on empiric data only
– Carries risk of suboptimal dosing and not achieving full
efficacy potential of rituximab
 Current study investigated serum levels and
pharmacokinetic parameters of rituximab when combined
with CHOP among elderly patients treated in RICOVER-60
study
Pfreundschuh M, et al. ASCO 2012. Abstract 8024.

Lymphomas
Rituximab Clearance and Elimination
 More rapid clearance of rituximab in male vs female
patients
– T1/2 in serum: 24.7 vs 33.4 days (P = .003)
– Correlated with poorer PFS in males (RR: 1.59; P < .01)
 Simulation of rituximab serum levels showed gradual
rituximab accumulation over treatment cycles
 Significantly improved PFS observed with addition of
rituximab among females < 60 kg (P = .002) but not
among females >77 kg

Lymphomas
Expert Perspectives
 Data emphasizes the fact that patients may not
necessarily require new drugs to achieve better outcomes
 Simply ensuring the existing agents (eg, rituximab) are
given with an optimal dose and schedule may help to
improve patient outcomes
 Current study limited by lack of data demonstrating how
rituximab serum levels could be successfully altered to
achieve better concentrations

Lymphomas
LNH 03-6B GELA: Study Design
 Final analysis of a multicenter, prospective, randomized
phase III trial
– Median follow-up: 56 mos
Delarue R, et al. ASCO 2012. Abstract 8021.
Treatment-naive
patients with
CD20-positive
stage II-IV DLBCL
aged 60-80 yrs
(N = 600)
CHOP-14 + Rituximab
+ Methotrexate*
(n = 304)
CHOP-21 + Rituximab
+ Methotrexate†
(n = 296)
CHOP-14 + Rituximab
CHOP-21 + Rituximab
Induction Consolidation
*Induction phase: 8 wks; consolidation phase: 10 wks.
†
Induction phase: 12 wks; consolidation phase 13 wks.
Response assessed at beginning of consolidation phase in both arms.

Lymphomas
LNH 03-6B GELA: Efficacy Outcomes
 No efficacy difference between different CHOP dosing regimens when
combined with rituximab in elderly DLBCL patients
Efficacy Outcome CHOP-14 + Rituximab
(n = 304)
CHOP-21 + Rituximab
(n = 296)
OR, %
CR/CRu
PR
87
71
16
86
74
12
3-yr EFS, % 56 60
 HR (95% CI) 1.04 (0.82-1.31; P = .76)
3-yr PFS, % 60 62
 HR (95% CI) 0.99 (0.78-1.26; P = .90)
3-yr DFS, % 72 67
 HR (95% CI) 0.80 (0.58-1.10; P =.16)
3-yr OS, % 69 72
 HR (95% CI) 0.96 (0.73-1.26; P = .75)

Lymphomas
LNH 03-6B GELA: Safety Outcomes
 14 patients in each arm died due to toxicity of study treatment
Adverse Events, % CHOP-14 + Rituximab
(n = 304)
CHOP-21 + Rituximab
(n = 296)
Hematologic toxicities
Grade 3/4 anemia
Grade 3/4 leukocytopenia
Grade 3/4 neutropenia
Grade 3/4 thrombocytopenia
Febrile neutropenia
Need for RBC transfusion
Need for platelet transfusion
22
78
74
16
21
47
11
18
73
64
20
19
32
8
Grade ≥ 3 nonhematologic toxicities 15 13
Grade 3/4 mucositis 5 3
≥ 1 adverse event 77 74
≥ 1 serious adverse event 51 47

Lymphomas
LNH 03-6B GELA: Expert Perspectives
 In the pre-rituximab era, superior OS seen with dose-
dense CHOP-14 regimen vs CHOP-21
 However, current study shows no survival difference
between CHOP-14 and CHOP-21 when rituximab is added
 Thus, R + CHOP-21 remains the standard of care

Lymphomas
Take-Home Points
 After further follow-up, bendamustine-rituximab appears to
have less toxicity and better PFS but still no OS benefit
compared with CHOP-R for patients with low-grade FL
 Lenalidomide + rituximab has a 70% response rate in
patients with FL relapsing after a rituximab-containing
regimen
 In the series presented here, transformation of FL to
DLBCL is lower with initial therapy containing rituximab
and lower still with maintenance rituximab

Lymphomas
Take-Home Points
 The EORTC found no significant difference in median OS
or EFS using BEACOPP versus ABVD in patients with
stage 3-4 Hodgkin lymphoma
 Retreatment with brentuximab vedotin after progression
following an initial response yielded a response rate of
60% in Hodgkin’s lymphoma and 88% in ALCL
 Rituximab clearance varies by sex and weight in elderly
patients and this variation may impact treatment outcome,
but we currently lack a practical approach to adjust dosing

Go Online for More CCO
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oncology/hematology conferences
Interactive Cases: compare your treatment decisions with your peers
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