1. Phase II SAKK 35/10 Trial: Rituximab Plus Lenalidomide Shows Durable Activity in Untreated Follicular Lymphoma
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.
This activity is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck, and Seattle Genetics.

2. Rituximab + Lenalidomide in Untreated Follicular Lymphoma (SAKK 35/10): Background
Rituximab achieves long-term remissions in pts with FL; however, most pts ultimately relapse[1-3]
Rituximab plus lenalidomide showed high activity in open-label, single-arm phase II study[4]
SAKK 35/10: randomized phase II study comparing rituximab plus lenalidomide vs rituximab alone in treatment-naive FL pts in need of therapy
Primary results showed significantly higher CR/CRu rate for lenalidomide plus rituximab (IRR: 61% vs 36%), with higher but manageable toxicity[5,6]
Current analysis reported results of SAKK 35/10 secondary endpoints, including PFS, TTNT, CR/CRu duration, CR/CRu at 30 mos, and OS[6]
CRu, unconfirmed CR; FL, follicular lymphoma; IRR, independent response review; TTNT, time to next lymphoma treatment.
1. Martinelli G, et al. J Clin Oncol. 2010;28: Taverna C, et al. J Clin Oncol. 2016;34: Kimby E, et al. Leuk Lymphoma. 2015;56: Fowler NH, et al. Lancet Oncol. 2014;15: Kimby E, et al. ASH Abstract Kimby E, et al. ASH Abstract 1099.
Slide credit: clinicaloptions.com

3. SAKK 35/10: Study Design Randomized phase II study
Primary endpoint: CR/CRu rate at Wk 23 (defined by NCI criteria)
Secondary endpoints: PFS, TTNT, CR duration, CR/CRu at 30 mos, and OS
Treatment-naive pts with
grade 1, 2, 3A FL in need of therapy
(N = 154)
Rituximab 375 mg/m2 IV on Day 1 of Wks 1-4,
Lenalidomide 15 mg/day*
(n = 77)
Rituximab 375 mg/m2 IV on Day 1 of Wks1-4, 12-15
Stratified by FL grade 1-2 vs 3a, bulky vs no bulk, FLIPI score 1, 2 vs ≥ 3, site
First restaging
Wk 10†
Second restaging
Wks 22-24
*Started 14 days before the first rituximab treatment, continued until 14 days after the last treatment.
†If no CR/PR/MR (MR > 25% decrease in SPD), then study treatment discontinued.
Follow-up
CRu, unconfirmed CR; FL, follicular lymphoma; FLIPI, Follicular Lymphoma International Prognostic Index; MR, minimal response; NCI, National Cancer Institute; SPD, sum of products of tumor diameters; TTNT, time to next lymphoma treatment.
Slide credit: clinicaloptions.com
Kimby E, et al. ASH Abstract 1099.

4. SAKK 35/10: Baseline Characteristics
Rituximab + Lenalidomide (n = 77)
Rituximab (n = 77)
Female, n (%)
42 (55)
40 (52)
Median age, yrs (range)
61 (26-80)
63 (29-85)
Stage, n (%) II
III IV
11 (14)
29 (38)
37 (48)
8 (10)
FLIPI, n (%)
Low risk
Intermediate risk
High risk
21 (27)
20 (26)
36 (47)
15 (19)
26 (34)
FLIPI, Follicular Lymphoma International Prognostic Index.
Slide credit: clinicaloptions.com
Kimby E, et al. ASH Abstract 1099.

5. Rituximab + Lenalidomide (n = 77)
SAKK 35/10: Efficacy
Median follow-up: 3.5 yrs
Endpoint
Rituximab + Lenalidomide (n = 77)
Rituximab (n = 76)
HR (95% CI)
P Value
Median PFS, yrs
Not reached
2.3
0.58 ( )
.03
CR/CRu duration, yrs
0.43 ( )
.04
TTNT, yrs
2.1
0.56 ( )
.01
CR/CRu at 30 mos, % 42 19 --
.001
3-yr OS, % 93 92
CRu, unconfirmed CR; TTNT, time to next lymphoma treatment.
Slide credit: clinicaloptions.com
Kimby E, et al. ASH Abstract 1099.

6. SAKK 35/10: Safety and Treatment Discontinuation
21% (16/77) of pts on rituximab arm and 4% (3/77) of pts on combination arm discontinued study therapy due to SD/PD at Wk 10
16% (12/77) of pts in combination arm discontinued lenalidomide only
11 pts due to toxicity
2 more pts discontinued lenalidomide due to toxicity, never started rituximab
Grade 3/4 AEs, n (%)
Rituximab + Lenalidomide (n = 77)
Rituximab (n = 76)
Fatigue
2 (2.6)
1 (1.3)
Allergic reaction --
Neutropenia
18 (23.4)
5 (6.6)
Thrombocytopenia
3 (3.9)
Depression
Psychosis
Suicide attempt
Maculopapular rash
4 (5.2)
Hypertension
7 (9.1)
AE, adverse event; PD, progressive disease; SD, stable disease.
-- Not reported
Slide credit: clinicaloptions.com
Kimby E, et al. ASH Abstract 1099.

7. SAKK 35/10: Conclusions
Investigators conclude that rituximab plus lenalidomide is an active, feasible therapy for pts with untreated FL
Significantly increased CR/CRu observed at Wk 23 in combination arm maintained through 30 mos (42% vs 19% for rituximab alone, P = .001)
Significantly prolonged CR/CRu duration (P = .04), PFS (P = .03), and TTNT (P = .01) observed for rituximab plus lenalidomide vs rituximab monotherapy
3-yr OS more than 90% in both arms
Authors suggest results warrant further exploration of chemotherapy- free strategies like rituximab plus lenalidomide
CRu, unconfirmed CR; FL, follicular lymphoma; TTNT, time to next lymphoma treatment.
Slide credit: clinicaloptions.com
Kimby E, et al. ASH Abstract 1099.

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