cco clin onc_june _2012_lymphoma_slides

June 1-5, 2012Chicago, Illinois

Lymphoma CCO Independent Conference Highlightsof the 2012 American Society of Clinical Oncology Annual Meeting*

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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


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)


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

FLFLIPI 0-2FLIPI 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


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

OS

Rat

e (%

)

2 3 4 5Follow-Up (Yrs)

6 7

50

B-RCHOP-R


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 toxicitiesLymphocytopeniaLeukocytopeniaNeutropeniaThrombocytopeniaAnemia

74372953

43726965

All-grade nonhematologic toxicitiesInfectious complicationsSkin (erythema)Allergic skin reactionParesthesiasStomatitisSepsis

36.816.115.36.96.10.4

50.29.15.9

28.918.63.2

.0025

.0122

.0003< .0001< .0001.0190


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”



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 1Lenalidomide: 15 mg cycle 1, then 20-25 mg cycles 2-12 on Days 1-21; dose escalated as toleratedAspirin 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


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)


ORR, %CRPR

72.736.436.4

51.113.337.8

EFSMedian EFS, yrs2-yr EFS, %

2.0*44

1.227

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.


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)


Hematologic toxicitiesNeutropeniaThrombocytopenia

1910

160

Nonhematologic toxicitiesFatigueRashThrombosisInfection

14840

94

164


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.


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.

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 Days 1, 6, 48, 90, 134, and 141CHOP-RIT: 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 Days 1, 6, 48, 90, 134, and 141; followed by dosimetric infusion of tositumomab/131I-tositumomab followed 1 wk later by 131I-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 2-M level (elevated vs not elevated)

2 wks


SWOG S0016/CALGB 50102: Predictive Factors for PFS Interaction With Treatment 2-M level only baseline factor significantly predictive of PFS

interaction with treatment arm in univariate analysis

No baseline factors significantly predictive of OS interactionPress 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


SWOG S0016/CALGB 50102: Predictive Value of FLIPI and FLIPI-2 Models Both FLIPI and FLIPI-2 models predictive of PFS and OS in

univariate analysis

Press OW, et al. ASCO 2012. Abstract 8001.

0

10

20

30

40

50

60

70

80

90

100

FLIPI FLIPI-2

Risk Group Models

5-Y

r P

FS

(%

)

LowIntermediateHigh

0

10

20

30

40

50

60

70

80

90

100

FLIPI FLIPI-2

Risk Group Models

5-Y

r O

S (

%)


SWOG S0016/CALGB 50102: Predictive Value of Lab-Based Risk Model Lab-based risk model developed using 2-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-basedrisk 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%


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

PFSFLIPIFLIPI-2Lab based (150% cut point)Lab based (90% 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

OSFLIPIFLIPI-2Lab based (150% cut point)Lab based (90% cut point)

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


SWOG S0016/CALGB 50102: Treatment Outcome by Patient Subgroup Patient subgroups defined by 2-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 levelsNormalElevated

6159

7657

.02

Lab-based risk model*LowIntermediateHigh

635430

705810

.03

*Using 150% of IULN.


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

– 2-M

– Lab-based risk model

Patient subgroups defined by β2-M levels and lab-based risk categories may experience different outcomes to treatment



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 Days 1-5; rituximab 375 mg/m2 on Day 1CHOP-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/m2 on Days 1-5; rituximab 375 mg/m2 on Day 1FM-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 foradditional 5 cycles

CHOP-R foradditional 3 cycles*

FM-R foradditional 3 cycles*

≥ PRStratified by FLIPI score (0-2 vs 3-5)

*Followed by 2 cycles of rituximab.


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.


FOLL05: Response


0

10

20

30

40

50

60

70

80

90

Res

po

nse

Rat

e (%

)

OR CR PR SD, PD, or EW

Depth of Response

10088

93 91 91

6772 72 70

21 21 19 20

88611

CVP-R

CHOP-R

FM-R

Overall


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)Federico M, et al. ASCO 2012. Abstract 8006.

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


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.


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.


Impact of Immunochemotherapy on FL 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.


Impact of Immunochemotherapy on FL 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.


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, 43Dose-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 on Day 1; vincristine 1.4 mg/m2 on Day 8; procarbazine 100 mg/m2 on Days 1-7; prednisone 40 mg/m2 on Days 1-14BEACOPP: 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 on Day 1; vincristine 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)

BEACOPPdose-escalated

(n = 274)

Primary endpoint: EFS from time of randomization

BEACOPPbaseline

BEACOPPbaseline

ABVD ABVD

4 cycles 2 cycles 2 cycles

Stratified by institution and IPS (3 vs ≥ 4)

If PR≥ 50%

If PR≥ 75%or CRu


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 69.30.86

(0.64-1.15).313

PFS 69.4 84.00.50

(0.34-0.73).0003

OS 86.7 90.30.71

(0.42-1.21).208


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)



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



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.


Phase II Brentuximab Vedotin Retreatment 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, %CRPR

703930

602040

887513

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.


Phase II Brentuximab Vedotin Retreatment 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



Phase II Brentuximab Vedotin Retreatment 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)



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.


Elderly Subpopulations of RICOVER-60: 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



Elderly Subpopulations of RICOVER-60: 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



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.


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/CRuPR

877116

867412

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)


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 toxicitiesGrade 3/4 anemiaGrade 3/4 leukocytopeniaGrade 3/4 neutropeniaGrade 3/4 thrombocytopeniaFebrile neutropeniaNeed for RBC transfusionNeed for platelet transfusion

22787416214711

1873642019328

Grade ≥ 3 nonhematologic toxicities 15 13

Grade 3/4 mucositis 5 3

≥ 1 adverse event 77 74

≥ 1 serious adverse event 51 47


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



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


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

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