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.

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;28:4480-4484. 2. Taverna C, et al. J Clin Oncol. 2016;34:495-500. 3. Kimby E, et al. Leuk Lymphoma. 2015;56:2598-2607. 4. Fowler NH, et al. Lancet Oncol. 2014;15:1311-1318. 5. Kimby E, et al. ASH 2014. Abstract 799. 6. Kimby E, et al. ASH 2016. Abstract 1099. Slide credit: clinicaloptions.com

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, 12-15 + 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 2016. Abstract 1099.

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 2016. Abstract 1099.

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 (0.36-0.94) .03 CR/CRu duration, yrs 0.43 (0.19-0.99) .04 TTNT, yrs 2.1 0.56 (0.35-0.89) .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 2016. Abstract 1099.

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 2016. Abstract 1099.

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 2016. Abstract 1099.

Go Online for More CCO Coverage of ASH 2016! Short slideset summaries of all the key data Additional CME-certified analyses with expert faculty commentary on all the key studies in: Leukemias Lymphomas/CLL Myeloma/plasma cell disorders MDS and myeloproliferative neoplasms clinicaloptions.com/oncology