San Diego, California—Lenalidomide combined with obinutuzumab is highly effective for advanced, previously untreated follicular lymphoma (FL) while retaining a manageable safety profile, according to clinical trial data presented at the 2018 ASH Annual Meeting.

“Obinutuzumab is a type II anti-CD20 monoclonal antibody that induces antibody-dependent cellular cytotoxicity, antibody-dependent cell-mediated phagocytosis, and direct cell death better than rituximab,” explained Franck Morschhauser, MD, University Lille, CHU Lille, France, and colleagues.

Lenalidomide combined with rituximab previously showed promising results, leading Dr Morschhauser and colleagues to conduct a large phase 1b/2 study assessing the safety and efficacy of lenalidomide combined with obinutuzumab (GALEN) in patients with advanced, untreated FL in need of systemic therapy.

The study enrolled 100 patients with World Health Organization (WHO) FL (90% grade 1-2; 9% grade 3), according to local pathology reports. Induction treatment consisted of lenalidomide 20 mg on days 1-21 of a 28-day cycle for the first cycle and on days 2-22 of a 28-day cycle from cycles 2 to 6. Obinutuzumab 1000 mg was given intravenously on days 8, 15, and 22 of cycle 1 and day 1 of cycles 2 to 6.

Patients who experienced a response went on to receive maintenance with lenalidomide at 10 mg on days 2-22 every 28 days for 12 cycles and obinutuzumab 1000 mg every 8 weeks for 12 cycles until progression or unacceptable toxicity.

The primary endpoint was complete response (CR) or CR unconfirmed (Cru) rate by investigator assessment at the end of induction according to 1999 IWG criteria. Secondary endpoints included overall response rate (ORR), CR according to IWG 2007, progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety.

All 100 patients enrolled in the trial were evaluable for safety and efficacy. At a median follow-up of 2.1 years, 96 patients completed induction, 41 completed maintenance, 36 were ongoing in maintenance, and 23 discontinued treatment due to disease progression (n=12) toxicity (n=6), concurrent illness (n=3), consent withdrawal (n=1), or other cause (n=1).

At the end of induction, 61 patients had regression by more than 75% of sum of the product of the greatest diameters (SPD) of target lesions. Of 97 patients with PET assessment 83 (85.6%) assessment were PET negative including 79 (84.9%) of 93 patients with a 5PS score of 1-3.

Sixteen patients with SPD regression >75% and 25 pts with negative PET were conservatively downgraded to partial response due to missing bone marrow evaluation, leading to 47% CR/CRu rate and 59% CR rate at the end of induction per IWG1999 and 2007 criteria, respectively.

The most common adverse events occurring in >10% of patients during induction were neutropenia, asthenia, constipation, infusion-related reactions, diarrhea, rash, cough, nausea, pruritus, weight decrease, bronchitis, muscle spasms, and pyrexia. Febrile neutropenia occurred in 2% of pts.

Dr Morschhauser and colleagues reported 8 second primary malignancies were reported in 8 patients, including 2 deemed unrelated since they were misdiagnosed at baseline. Three patients had died, 1 each due to lymphoma, toxicity of additional treatment, and intestinal adenocarcinoma.

“The immunomodulatory GALEN regimen is highly effective with no unexpected toxicity in advanced, untreated FL pts in need of systemic therapy and has the potential to challenge immunochemotherapy in this setting,” Dr Morschhauser and colleagues concluded.—Janelle Bradley

Morschhauser F, Salles GA, Casasnovas RO, et al. A Phase II Lysa Study of Obinutuzumab Combined with Lenalidomide for Advanced Untretated Follicular B-Cell Lymphoma in Need of Systemic Therapy. Presented at: the 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 446.