Follicular Lymphoma Transformed Lymphoma Diffuse Large B-Cell Lymphoma John P. Leonard, M.D. Richard T. Silver Distinguished Professor of Hematology and Medical Oncology Professor of Medicine, Weill Cornell Medical College Associate Director, Weill Cornell Cancer Center
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Follicular Lymphoma Transformed Lymphoma Diffuse Large B-Cell Lymphoma
Follicular Lymphoma Transformed Lymphoma Diffuse Large B-Cell Lymphoma. John P. Leonard, M.D. Richard T. Silver Distinguished Professor of Hematology and Medical Oncology Professor of Medicine, Weill Cornell Medical College Associate Director, Weill Cornell Cancer Center. - PowerPoint PPT Presentation
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Follicular LymphomaTransformed Lymphoma
Diffuse Large B-Cell Lymphoma
John P. Leonard, M.D.Richard T. Silver Distinguished Professor of Hematology
and Medical Oncology
Professor of Medicine, Weill Cornell Medical College
Bendamustine 90 mg/mBendamustine 90 mg/m22 day 1+2 + R day 1, max 6 cycles, q 4 wks. day 1+2 + R day 1, max 6 cycles, q 4 wks. CHOP-R, max 6 cycles, q 3 wks.CHOP-R, max 6 cycles, q 3 wks.
Rummel et al.: Rummel et al.: BloodBlood 114: 168 (abstr #405), 2009 114: 168 (abstr #405), 2009
B-R vs CHOP-R - Toxicities (all CTC-grades)B-R vs CHOP-R - Toxicities (all CTC-grades)
B-R (n = 260) CHOP-R (n = 253)
(no. of pts) (no. of pts) p-value
Alopecia – +++ < 0.0001
Paresthesias 18 73 < 0.0001
Stomatitis 16 47 < 0.0001
Skin (erythema) 42 23 = 0.0122
Allergic reaction (skin)
40 15 = 0.0003
Infectious complications
96 127 = 0.0025
- Sepsis 1 8 = 0.0190
Median Progression-Free Survival Median Progression-Free Survival
Rummel et al.: Rummel et al.: BloodBlood 114: 168 (abstr #405), 2009 114: 168 (abstr #405), 2009
BR, 54.9 months vs CHOP-R, 34.8 months
Hazard ratio, 0.57
p-value = 0.00012
Progression-Free Survival: Subentities
BR vs CHOP-R:
• Follicular, p = 0.0281
• Mantle cell, p = 0.0146
• Marginal zone, p = 0.6210
• Waldenström, p = 0.0024
Rummel et al.: Rummel et al.: BloodBlood 114: 168 (abstr #405), 2009 114: 168 (abstr #405), 2009
Randomized Trial of Rituximab VersusWatch-and-Wait in Stage II-IV Asymptomatic
Nonbulky Follicular Lymphoma: Study Design
Randomized Trial of Rituximab VersusWatch-and-Wait in Stage II-IV Asymptomatic
Nonbulky Follicular Lymphoma: Study Design
Ardeshna et al. ASH 2010; abstract 6.Ardeshna et al. ASH 2010; abstract 6.
Primary endpoint: time to initiation of new therapy
Preliminary analysis of rituximab vs. watch and wait in stage II-IV, asymptomatic, non-bulky FL:
Efficacy and safety
Preliminary analysis of rituximab vs. watch and wait in stage II-IV, asymptomatic, non-bulky FL:
Efficacy and safety
Ardeshna et al. ASH 2010, Abstract 6.
Response at 25 monthsArm A
(N = 187)Arm B
(N = 84)Arm C
(N = 192)
ORR 8% 53% 79%
CR/CRu 4% 40% 70%
PR 4% 13% 9%
Initiated new treatment 44% 23% 10%
HR for median TTNT0.37
(34 months)0.20 0.57
No treatment at 3 years 48% 80% 91%
3-year PFS 33% 60%81%
(P < 0.001 vs. A)
3-year OS 95% (no significant difference)
Safety
Serious adverse events 14 6 25
Preliminary analysis of rituximab vs. watch and wait in stage II-IV, asymptomatic, non-bulky FL
Preliminary analysis of rituximab vs. watch and wait in stage II-IV, asymptomatic, non-bulky FL
With permission from Ardeshna et al. ASH 2010, Abstract 6.
HR (Rituximab vs W+W) = 0.37, 95% CI = 0.25, 0.56, p < 0.001HR (Rituximab + M vs W+W) = 0.20, 95% CI = 0.13, 0.29, p < 0.001HR (Rituximab + M vs Rituximab) = 0.57, 95% CI = 0.29, 1.12, p = 0.10
Proportion of patients with
no new treatment initiated
Preliminary analysis of rituximab vs. watch and wait in stage II-IV, asymptomatic, non-bulky FL
Preliminary analysis of rituximab vs. watch and wait in stage II-IV, asymptomatic, non-bulky FL
With permission from Ardeshna et al. ASH 2010, Abstract 6.
HR (Rituximab vs W+W) = 0.46, 95% CI = 0.33, 0.65, p < 0.001HR (Rituximab + M vs W+W) = 0.21, 95% CI = 0.15, 0.29, p < 0.001HR (Rituximab + M vs Rituximab) = 0.43, 95% CI = 0.24, 0.72, p = 0.001
PRIMA: Study designPRIMA: Study design
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
Registration
* Stratified by response after induction, regimen of chemo and geographic region‡ Frequency of clinical, biological and CT-scan assessments identical in both armsFive additional years of follow-up
Salles et al, ASH 2010.
Primary endpoint (PFS): 36 monthsfollow-up
Primary endpoint (PFS): 36 monthsfollow-up
Salles GA et al. Proc ASH 2010;Abstract 1788.
Observationn = 513
R Maintenancen = 505
3-yr progression-free survival (PFS)
58% 75%
Hazard ratio (95% CI) 0.55 (0.44-0.68)
p-value <0.0001
Safety during rituximab maintenanceSafety during rituximab maintenance