Elucidating First-Line SC Mosunetuzumab Benefit in Follicular Lymphoma

At the European Hematology Association (EHA) 2026 Congress, Emmanuel Bachy, MD, PhD, discussed findings from the phase 1b/2 CO41942 study (NCT04246086), which evaluated the efficacy and the safety profile of subcutaneous mosunetuzumab (Lunsumio VELO) in patients with follicular lymphoma with a high tumor burden. The investigative regimen utilized an induction phase combining the subcutaneous CD20/CD3 bispecific antibody with the immunomodulatory agent lenalidomide (Revlimid) for 12 months, followed by optional mosunetuzumab maintenance therapy.

The primary objectives focused on safety and efficacy, yielding promising results among the 43 enrolled patients. At a median follow-up of 30.6 months, responses were durable with a 24-month progression-free survival (PFS) rate of 87%. The combination also achieved a best overall response rate (ORR) of 90% and a complete response (CR) rate of 88%. Notably, these outcomes compare favorably with historical data from the phase 3 GALLIUM study (NCT01332968), where conventional immunochemotherapy benchmarks reached a 70% to 75% complete metabolic response (CMR).²

With mosunetuzumab and lenalidomide, the safety profile proved manageable; toxicities included expected cytopenias and low-grade cytokine release syndrome (CRS), with no instances of immune effector cell-associated neurotoxicity syndrome (ICANS) or grade 5 adverse effects (AEs). This study effectively established the proof of concept and hypothesis for the ongoing phase 3 MorningLyte trial (NCT06284122) comparing this regimen directly against standard immunochemotherapy.³

Bachy is a co-chair of the Clinical Hematology Department and an associate professor of Hematology at Lyon Sud Hospital in Lyon, France.

CancerNetwork: What were the key aspects of the study design and enrollment criteria?

Bachy: We presented the data on a study about the use of subcutaneous mosunetuzumab. Mosunetuzumab is a CD20×CD3 bispecific antibody that was combined with lenalidomide, an immunomodulatory agent. The trial enrolled patients with follicular lymphoma in the first-line setting; the patients needed to have a high tumor burden criterion, at least according to the GELF criteria. It is quite a general patient population with high tumor burden in the frontline setting of follicular lymphoma.

There were 2 phases [of the study]. The first one was an induction phase of 12 months where mosunetuzumab was combined with lenalidomide. The first cycle was 3 weeks long for step-up dosing to mitigate the risk of CRS, followed by 11 cycles of one mosunetuzumab infusion every 4 weeks. Lenalidomide was administered orally from cycle 2 to cycle 12 at the usual dose in lymphoma of 20 mg per day from day 1 to day 21. 6his is the induction phase for 1 year. Then, the patients could enter the maintenance phase at the discretion of the investigator, which consisted of nine 8-week cycles of mosunetuzumab only. There was no lenalidomide during this phase. Overall, the treatment length was 30 months if the patient got through both the induction and the maintenance phases.

What were the key efficacy findings presented this year?

We presented the primary [end point] of the study, which was both the efficacy and the safety. Regarding the efficacy, the results were very impressive. The ORR was 90% in the 43 patients who were enrolled in the study, and the complete response rate was [88%]. Just as a reminder, if we make a comparison—it’s historical—in the GALLIUM study with conventional immunochemotherapy, we basically reached 70% to 75% of CMR; here, we got an [88%] CR rate, so very high.

The median follow-up is still quite short—it’s 30 months—but durable overall response and durable CR were observed, with a 2-year response duration of more than 90% as well as the duration of [CR]. Regarding the PFS and the overall survival [OS], they were also very high, with a high rate of 2-year PFS and OS. There was only 1 death throughout the study among the 43 patients, so very good results in this follicular lymphoma patient population with high tumor burden criteria.

What were the safety findings?

Overall, the safety profile was [aligned] with what we know for both products, with some rash following lenalidomide administration and some cytopenias, especially neutropenia, that sometimes led to treatment modification or [interruption]. Overall, the treatment was maintained for the vast majority of the patients, either during the induction phase or the maintenance phase. The treatment discontinuation [rate] was 14% during the induction phase and 12% during the maintenance phase. Overall, the safety profile was pretty good, and the patients could go until the end of the treatment.

One of the main AEs that was [observed] was the rate of CRS, which is known to occur with bispecific antibodies. It was only grade 1 to 2 CRS. There were no grade 3 or grade 4 CRS events, and only 2 patients experienced grade 2 CRS; the vast majority was grade 1 CRS. [Additionally,] there was no ICANS––no neurotoxicity––at all. There were very few patients with grade 3 or 4 infections, which is another concern with bispecific antibodies; we saw a very low rate of infection, especially during the maintenance phase. Because of this, you can ask the question of whether the maintenance is really needed, and if the balance between the risk and the benefit is still there when we use maintenance with bispecific antibodies. The results were [quite] encouraging regarding the safety profile, both during the induction and the maintenance phases.

What are the next steps for these treatments, and what areas of research should be explored next?

This was a phase 1b study, and this was the study that set the stage for the phase 3 randomized trial that is currently ongoing, the MorningLyte trial. That trial is comparing this exact same regimen, with an induction phase of subcutaneous mosunetuzumab plus lenalidomide, followed by the maintenance phase of the exact same duration. It’s [randomly assigning patients] between this new experimental treatment compared with conventional immunochemotherapy, either rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP], obinutuzumab [Gazyva] plus CHOP [G-CHOP], or bendamustine-based regimens like rituximab/bendamustine or obinutuzumab/bendamustine. The study is still ongoing. We will have the results in a few years, but this phase 1b study generated the hypothesis for running a phase 3 study.

References

1. Bachy E, Morschhauser F, Eyre TA, et al. Safety and efficacy of subcutaneous mosunetuzumab plus lenalidomide induction therapy followed by mosunetuzumab maintenance in previously untreated follicular lymphoma. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S226.
2. Townsend W, Hiddemann W, Buske C, et al. Obinutuzumab versus rituximab immunochemotherapy in previously untreated iNHL: final results from the GALLIUM study. Hemasphere. 2023:7(7):e919. doi:10.1097/HS9.0000000000000919
3. Study of mosunetuzumab plus lenalidomide compared to anti-CD20 anti-body + chemotherapy in follicular lymphoma FLIPI2-5 (MorningLyte). ClinicalTrials.gov. Updated June 5, 2026. Accessed June 15, 2026. https://tinyurl.com/5ac734ym