Mosunetuzumab Elicits High, Durable Responses in Multiply Relapsed Follicular Lymphoma

Mazyar Shadman, MD, MPH

Fixed-duration treatment with mosunetuzumab elicited encouraging responses with acceptable safety when used in patients with multiply relapsed follicular lymphoma, according to data from the phase 1/2b GO29781 trial (NCT02500407) presented during the 2021 Pan Pacific Lymphoma Conference.¹

Among all 62 patients with follicular lymphoma, the full-length, fully humanized immunoglobulin G1 CD20xCD3 bispecific antibody elicited an objective response rate (ORR) of 67.7% (n = 42) with a complete response (CR) rate of 51.6% (n = 32). The agent also showcased high and consistent response rates in high-risk subsets.

In 4 patients who previously received CAR T-cell therapy, the ORR was 100% with a CR rate of 50.0%. In patients who were refractory to PI3K inhibitors (n = 13), in those who had progression of disease within 24 months (POD24; n = 29), in those who were double refractory (n = 38), and in those who were refractory to their last previous therapy received (n = 46), the ORRs were 92.3%, 75.9%, 71.1%, and 65.2%, respectively. The CR rates in these subsets were 84.6%, 55.2%, 50.0%, and 47.8%, respectively.

Additionally, the time to median follow-up following first response to treatment was 18.4 months (range, 2-34). The median duration of response (DOR) was 20.4 months (95% CI, 9.4-22.7); in those who had achieved a CR with mosunetuzumab, the median DOR was 21.0 months (95% CI, 16.0-22.7).

“Fixed duration of mosunetuzumab induces high and consistent response rates across multiple high-risk follicular lymphoma subsets, with durable responses,” study author Mazyar Shadman, MD, MPH, associate professor of Medical Oncology at the University of Washington said during a poster presentation on the data. “Assessment of higher dose levels is ongoing to maximize efficacy.”

Although therapeutic options have emerged for follicular lymphoma over the years, the disease is characterized by recurrent relapse and remains incurable. For those who have previously received 2 or more systemic therapies, options are limited, and patients are known to have a poor prognosis. Mosunetuzumab was designed to redirect T cells to engage and eliminate malignant B cells.

The ongoing phase 1/2b study enrolled patients with grade 1 to 3a relapsed/refractory follicular lymphoma who were expected to express CD20. To be eligible for enrollment, patients needed to be at least 18 years of age, have received 2 or more prior systemic therapies, had an ECOG performance status of 0 or 1.

Study participants were given intravenous mosunetuzumab as step doses in cycle 1 on days 1 and 8, followed by target doses on day 15 and day 1 of each subsequent 21-day cycle. Patients who achieved a CR by cycle 8 discontinued treatment. Patients who experienced a partial response or stable disease were able to continue treatment for up to 17 cycles until disease progression or intolerable toxicity.

The primary objectives of the trial included efficacy of the agent, identifying the recommended phase 2 dose, and examining the best objective response achieved with the treatment. Moreover, investigators examined the safety and tolerability of the agent, with a specific focus on dose-limiting toxicities and establishing the maximum-tolerated dose.

At a data cutoff of August 7, 2020, a total of 62 patients had been enrolled to the trial. Patients had a median age of 59 years (range, 27-85). The majority, or 64.5%, of patients were male, 59.7% had an ECOG performance status of 0, and the median number of prior therapies received was 3 (range, 2-11). Of the patients enrolled, 61.3% were double refractory and 46.8% had POD24.

All patients received prior anti-CD20 agents and alkylator therapy, 21.0% had received prior PI3K inhibitors, 19.4% previously underwent autologous stem cell transplant, 8.1% had prior immunomodulatory drugs, and 6.5% had prior CAR T-cell therapy. Moreover, 74.2% were refractory to their last previous therapy received and 87.1% were refractory to prior anti-CD20 therapy.

Regarding safety, mosunetuzumab was found to have an acceptable toxicity profile. Adverse effects (AEs) were experienced by 96.8% of patients and 35.5% experienced serious AEs. Additionally, 67.7% of patients experienced grade 3 or higher toxicities and 1.6% of patients experienced effects that were grade 5 in severity. The most frequent grade 3 or higher toxicities that were reported in more than 10% of participants were hypophosphatemia and neutropenia.

Five patients (8%) experienced AEs that resulted in treatment discontinuation and 4 of these effects were related to the study drug.

Any-grade cytokine release syndrome (CRS) was reported in 17.7% of 62 patients. Of these events, 16.1% had grade 1 CRS and 1.6% had grade 2. Of the CRS events reported, 6.5% were serious. The median onset of first CRS event was 1 day (range, 1-24) and the median duration was 2 days (range, 1-8).

All of these events resolved without the use of tocilizumab (Actemra), intensive care unit admission, or vasopressors. CRS signs and symptoms included pyrexia (17.7%), headache (4.8%), and tachycardia (3.2%). Notably, similar rates of CR were observed between those who had CRs (n = 5/11) and those who did not (n = 27/51), at 45.0% and 52.9%, respectively.

In an ongoing phase 3 clinical trial (NCT04712097), mosunetuzumab is under investigation in combination with lenalidomide (Revlimid) vs rituximab (Rituxan) plus lenalidomide in patients with follicular lymphoma following at least 1 line of systemic therapy.²

References

1. Assouline S, Kim WS, Sehn LH, et al. Updated experience from mosunetuzumab in multiply relapsed follicular lymphoma: promising efficacy from a phase 1 trial. Presented at: 2021 Pan Pacific Lymphoma Conference; August 9-13, 2021; Big Island, HI. https://bit.ly/3DfhFLN
2. A study evaluating the efficacy and safety of mosunetuzumab in combination with lenalidomide in comparison to rituximab in combination with lenalidomide in patients with follicular lymphoma after at least one line of systemic therapy. ClinicalTrials.gov. Updated July 29, 2021. Accessed August 24, 2021. https://clinicaltrials.gov/ct2/show/NCT04712097