Highlights from

ASCO 2019

American Society of Clinical Oncology annual meeting

Chicago, USA 31 May - 4 June 2019

Rituximab/lenalidomide regimen shows clinical benefit in non-hodgkin lymphoma trials

Medical writer: Tim Donald, ELS

Rituximab plus lenalidomide (R2) demonstrated significant clinical benefit in two trials in patients with indolent non-Hodgkin lymphoma (iNHL), according to abstracts to be presented during a Poster Session on June 3.

David Jacob Andorsky, MD, of Rocky Mountain Cancer Centres, US Oncology Research, will present interim analyses of the MAGNIFY trial (Abstract 7513). John G. Gribben, MD, Dsc, FRCP, FRCPath, FMedSci, of the Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, will present analyses of results from the AUGMENT trial (Abstract 7514).

Both trials included patients with previously treated follicular lymphoma (FL) and previously treated marginal zone lymphoma (MZL). The presentations are timely, as the U.S. Food and Drug Administration approved the use of lenalidomide in combination with rituximab for previously treated FL and previously treated MZL in the week before the ASCO Annual Meeting.

In an interview before the Annual Meeting, the discussant of the two presentations, Carla Casulo, MD, of the University of Rochester, Wilmot Cancer Institute, said the results “add value to the trajectory of treatment for FL.” With the approval of the R2regimen for this indication, she said, “we now have effective, durable, and well-tolerated treatment alternatives for patients with previously treated disease.”

MAGNIFY is a multicentre non-registrational phase IIIb trial in patients with relapsed or refractory FL, grade 1 to 3a, and MZL, designed to determine the optimal duration of lenalidomide. All patients received R2, consisting of lenalidomide 20 mg/d for days 1 to 21 of 28, plus rituximab 375 mg/m2 per week for one cycle and every 8 weeks for three cycles and above for 12 cycles. After this induction phase, patients with stable disease or better were randomly assigned 1:1 to continued R2 vs. rituximab maintenance. The primary endpoint was overall response rate (ORR) for induction R2 in efficacy-evaluable patients receiving one or more treatments. Baseline and post-baseline assessments were conducted.

With a median 16.7 months follow-up, 370 patients (80% with FL and 20% with MZL) were enrolled. Median age was 66, and 83% of patients had stage III or stage IV disease and a median of two prior therapies, 95% of which included rituximab. Efficacy-evaluable patients showed a 73% ORR, and 45% showed a complete response (CR). Median time to relapse was 2.7 months, and median progression-free survival (PFS) was 36.0 months.

In an exploratory analysis, Dr. Andorsky explained, response rate was stratified by several risk factors known to be associated with adverse outcomes for FL. These included rituximab-refractory status, double-refractory (refractory to both rituximab and an alkylating agent) status, and early relapse.

“There was significant clinical benefit [in response rate], even in patients with rituximab-refractory disease, the patients with double-refractory disease, and the patients who experience early relapse,” Dr. Andorsky said. “The study supports that, even in those high-risk populations, this is a beneficial therapy and one that’s well tolerated.”

AUGMENT was a phase III study evaluating patients with relapsed or refractory FL grade 1 to grade 3a (82%) and MZL (18%) after one or more prior systemic therapy. In one difference from MAGNIFY, patients with rituximab-refractory disease were not included. Patients were randomly assigned 1:1 to R2 or to rituximab/placebo (R/placebo) with the same dosing schedule. The primary endpoint was PFS. Secondary and exploratory analyses included time to next anti-lymphoma or chemotherapy treatment (TTNLT/TTNCT) and response to next treatment.

Median PFS was superior for R2 over R/placebo (39.4 vs. 14.1 months; HR 0.46; P < 0.0001). As of June 2018, median TTNLT, TTNCT, and progression after next line of therapy (PFS2) were not reached for R2 and were significantly longer for R2 than for R/placebo (HR 0.54, 0.50, and 0.52, respectively). For 49 of 178 (28%) R2 and 80 of 180 (44%) R/placebo patients receiving next anti-lymphoma therapy, response was generally higher with R2 (57% ORR; 31% CR) than with R/placebo (36% ORR; 16% CR).

The AUGMENT investigators concluded that R2 prolonged time to subsequent treatment compared with R/placebo, and that R2 was associated with longer PFS2, enabling greater response to next therapy.

“What I find most interesting about these abstracts,” Dr. Casulo said, “is that we see efficacy in high-risk subgroups (as reported in MAGNIFY) such as patients with early relapsing FL and double-refractory FL, populations that historically have poor outcomes. In the AUGMENT secondary and exploratory endpoints reported in this abstract [7514], we see that lenalidomide and rituximab have a longer time to next treatment and longer PFS2 after next treatment. This is an important contribution since historically, response rates and duration of response decrease with subsequent therapies in FL. It suggests that lenalidomide and rituximab could render patients more sensitive to subsequent therapies (compared with R/placebo), although since the numbers are small and some of these were exploratory objectives, results should be interpreted with caution.”

Top image: @ Science Photo Library: Steve Gschmeissner

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.