1. REMARC: Lenalidomide vs Placebo as Maintenance Therapy in Patients With DLBCL Following R-CHOP Induction
New Findings in Hematology: Independent Conference Coverage of ASH 2016*; December 3-6, 2016; San Diego, California
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
DLBCL, diffuse large B-cell lymphoma; R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone.
This activity is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck, and Seattle Genetics.

2. REMARC: Lenalidomide Maintenance Therapy Following First-line R-CHOP for DLBCL
Rituximab plus CHOP is preferred therapy for DLBCL
LNH-98.5 trial observed 10-yr PFS of 36.5% with R-CHOP vs 20.1% with CHOP alone in elderly pts with DLBCL (P < .0001)[1]
In this trial, most pts (~ 40% with R-CHOP and ~ 60% with CHOP) relapsed within 2 yrs[1]
Studies evaluating addition of various agents to induction and maintenance R-CHOP have not reported evidence of benefit in DLBCL
MAIN study of bevacizumab induction (RA-CHOP) found no benefit[2]
PRELUDE[3] and PILLAR-2[4] studies of maintenance R-CHOP plus enzastaurin or everolimus found no benefit in 4-yr and 2-yr DFS, respectively
Current study assessed safety, efficacy of lenalidomide maintenance therapy following R- CHOP in elderly pts with DLBCL[5]
DLBCL, diffuse large B-cell lymphoma; R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone.
1. Coiffier B, et al. Blood. 2010;116: Seymour JF, et al. Haematologica. 2014;99: Crump M, et al. J Clin Oncol. 2016;34: Witzig TE, et al. ASCO Abstract Thieblemont C, et al. ASH Abstract 471.
Slide credit: clinicaloptions.com

3. maintenance treatment
REMARC: Study Design
Multicenter, randomized, double-blind, placebo-controlled phase III study
Primary endpoint: PFS, defined as first documented relapse or progression assessed by blinded independent review, or all-cause death
Secondary endpoints: safety, OS, conversion from PR to CR, efficacy by R-CHOP response
*25 mg/day for 21/28 days. Pts with CrCl < 30 mL/min received 10 mg lenalidomide.
Pts aged yrs with untreated DLBCL (histologically confirmed CD20+ per WHO 2008 criteria), FL3b, or de novo transformed follicular or indolent lymphoma, no major comorbidities
Up to 24-mo
maintenance treatment
duration
Lenalidomide*
(n = 323)
Placebo*
(n = 327)
R-CHOP
6-8 cycles
Stratified by CR vs PR status after R-CHOP induction
CR/PR
CrCl, creatinine clearance; DLBCL, diffuse large B-cell lymphoma; R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone; WHO, World Health Organization.
Slide credit: clinicaloptions.com
Thieblemont C, et al. ASH Abstract 471.

4. REMARC: Pt Characteristics
Lenalidomide
(n = 323)
Placebo
(n = 327)
Median age, yrs
70 yrs or older, n (%) 69
154 (48) 68
145 (44)
Male, n (%)
183 (57)
180 (55)
Response following R-CHOP, n (%) CR PR
ORR
251 (78)
69 (21)
320 (99)
244 (75)
83 (25)
327 (100)
R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone.
Slide credit: clinicaloptions.com
Thieblemont C, et al. ASH Abstract 471.

5. REMARC: Disease Characteristics
Histologic Diagnosis Classification, n (%)
Lenalidomide
(n = 290)
Placebo
DLBCL NOS
225 (78)
233 (80)
FL grade 3b
2 (1)
3 (1)
De novo transformed
31 (11)
16 (6)
Other*
32 (11)
38 (13)
*Includes B-cell lymphoma with features intermediate between DLBCL and Burkitt lymphoma or HD.
GCB/ABC Profile,* n (%)
Lenalidomide
(n = 151)
Placebo
(n = 167)
ABC
63 (42)
58 (35)
GCB
59 (39)
79 (47)
Unclassified
24 (16)
25 (15)
N/A
5 (3)
ABC, activated B-cell-like; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; GCB, germinal center B-cell-like; HD, Hodgkin lymphoma; N/A, not available; NOS, not otherwise specified.
*Profiled with commercial technology platform in DLBCL NOS only.
Slide credit: clinicaloptions.com
Thieblemont C, et al. ASH Abstract 471.

6. REMARC: Progression-Free Survival
Median PFS: NR in lenalidomide arm vs 58.8 mos in placebo arm (HR: 0.708; 95% CI: ; P = .0135) with a median follow-up of 40 mos
Lenalidomide significantly extended PFS in older pts, pts with CR response to R- CHOP, and positive PET scan at randomization
Pts aged 70 yrs or older: HR: 0.653; 95% CI:
CR response to R-CHOP: HR: 0.722; 95% CI:
Positive PET at randomization: HR: 0.592; 95% CI:
Lenalidomide trended toward prolonging PFS in GCB-positive DLBCL (P = .0742) but had no significant effect on PFS in ABC positive or unclassified disease
No significant differences observed between lenalidomide vs placebo in subgroups by country, sex, or age-adjusted international prognostic index
ABC, activated B-cell-like; DLBCL, diffuse large B-cell lymphoma; GCB, germinal center B-cell-like; NR, not reached; R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone.
Slide credit: clinicaloptions.com
Thieblemont C, et al. ASH Abstract 471.

7. REMARC: OS and Conversion From PR to CR
No significant differences in OS for lenalidomide vs placebo (HR: ; 95% CI: ; P = .2640) with a median follow-up of 52 mos
Similar rates of PR-to-CR conversion during maintenance period among pts with PR response to R-CHOP
CR achieved by 23 of 69 (33%) pts receiving lenalidomide vs 24 of 83 (29%) pts receiving placebo (P = .557)
Median time to conversion: 5.9 (range: ) vs 5.6 mos (range: ), respectively
R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone.
Slide credit: clinicaloptions.com
Thieblemont C, et al. ASH Abstract 471.

8. REMARC: Treatment Exposure and Safety
Median average dose was 19.8 mg (range: ) of lenalidomide vs 25.0 mg (range: ) of placebo
D/c due to toxicity occurred in 36% of lenalidomide pts vs 16% of placebo pts
≥ 1 dose reduction due to toxicity in 72% vs 42%, respectively
2 pts receiving placebo died due to toxicity
Secondary primary malignancies in 10% of lenalidomide pts vs 13% of placebo pts
Hematologic malignancy in 2% per arm
Solid tumor (excluding nonmelanoma skin cancer) in 4% vs 6%, respectively
Grade 3/4 TEAEs, %
Lenalidomide
(n = 322)
Placebo
(n = 323)
Neutropenia 56 22
Infection 8 6
Thrombocytopenia 3 1
Venous thromboembolism
0.3
Cutaneous reaction
Diarrhea and constipation 2
Hepatic disorder
Peripheral neuropathy
Cardiac disorders 5
D/c, discontinuation; TEAEs, treatment-emergent adverse events.
Slide credit: clinicaloptions.com
Thieblemont C, et al. ASH Abstract 471.

9. REMARC: Conclusions
Lenalidomide significantly prolonged median PFS vs placebo as maintenance therapy after R-CHOP in DLBCL (NR vs 58.8 mos, respectively; P = .0135)
No significant effect on OS with a median follow-up of 52 mos
Greater rate of grade 3/4 neutropenia and d/c for toxicity observed with lenalidomide vs placebo
Investigators concluded that in elderly pts with DLBCL who received first-line R-CHOP, use of lenalidomide maintenance therapy provides clinically meaningful PFS improvement
d/c, discontinuation; DLBCL, diffuse large B-cell lymphoma; NR, not reached; R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone.
Slide credit: clinicaloptions.com
Thieblemont C, et al. ASH Abstract 471.

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