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Mosunetuzumab Safe, Effective for Elderly Patients With DLBCL
Single-agent mosunetuzumab demonstrated efficacy, remarkable safety, as a chemotherapy-free option for previously untreated elderly/unfit patients with diffuse large B-cell lymphoma (DLBCL), according to findings from an open-label, multi-center, phase 1/2 study presented by Adam J. Olszewski, MD, Brown University, Providence, RI, at the virtual 62nd American Society of Hematology Annual Meeting and Exposition.
“Up to 30% of patients aged ≥75 years do not receive standard chemoimmunotherapy (CIT) as first-line treatment for [DLBCL] due to concerns about frailty and comorbidities. Poor outcomes are commonly reported for elderly/unfit patients with first-line DLBCL who receive no treatment, reduced-dose R-CHOP or other therapies such as R-CVP and R-bendamustine; less toxic, efficacious alternatives to full-dose CIT are needed,” wrote Dr Olszewski and colleagues.
Researchers reported data from Cohort B, which was designed to evaluate the safety, pharmacokinetics (PK), and preliminary efficacy of mosunetuzumab in patients with first-line DLBCL who are unable to tolerate full-dose CIT. Two safety evaluation cohorts planned to receive mosunetuzumab at 13.5 mg and 30 mg, followed by an expansion phase; after evaluating both cohorts, no safety concerns were found.
Eligible patients included those who were aged 80 years or older, as well as patients who were aged 60 to 79 years with impairment in ≥1 activity of daily living (ADL) or instrumental ADL, or with impairment in cardiac, renal, or liver function precluding the use of full-dose CIT.
Following an optional pre-phase treatment with prednisone with or without vincristine, eligible patients received mosunetuzumab intravenously with step-up dosing on days 1, 8, and 15 of cycle 1, followed by a fixed-dose on day 1 of each subsequent 21-day cycle, with an interim response assessment (IRA) occurring after cycle 4 and a primary response assessment (PRA) after cycle 8. Optional continuation of up to 17 cycles in case of partial remission (PR) was available following PRA.
Cohort B consisted of 19 patients, 14 (74%) of whom were women, with the median age being 84 (67-100 years), and 10 (53%) patients had Ann Arbor stage III-IV, and 17 (90%) had an IPI score ≥2. Eight patients were enrolled in the 13.5mg safety evaluation cohort and 11 enrolled in the 30mg safety cohort and expansion, the median mosunetuzumab cycles received was 6 (1 patient in PR continued treatment).
The overall response rate (ORR) for all patients was 58% (11/19 patients), and the complete response (CR) rate was 42% (8/19). 3 out of 8 patients (38%) receiving mosunetuzumab 13.5 mg achieved CR, 2 (25%) had a PR, and 3 (38%) had progressive disease (PD) at the time of PRA. Amongst patients receiving 30mg of mosun, 5/11 (45.5%) achieved a CR, 1 (9%) had a PR, and 5 (45.5%) had PD. Five of 8 total patients with PD received salvage therapy post-progression.
Adverse events (AEs) of grade 1 or higher occurred in 16 (84%) of patients, 13 (68%) patients experienced AEs related to mosunetuzumab. Furthermore, 7 (37%) experienced a grade 3-4 AE, 4 of which were related to mosunetuzumab.
The most common treatment-emergent AEs were cytokine release syndrome (CRS; n = 9, 47%), rash (n = 4, 21%), neutropenia, nausea, decreased appetite, dry mouth, fatigue, pain, and muscle spasms (all n = 2, 11%). There were no fatal AEs, nor were there severe neurologic AEs observed. Eight (42%) patients discontinued mosunetuzumab early due to PD, but no discontinuations were due to AEs.
“Early clinical data indicate that single-agent mosunetuzumab confers notable efficacy and remarkable tolerability for previously untreated elderly/unfit DLBCL patients. Mosunetuzumab is a promising chemotherapy-free regimen for patients who otherwise have limited options,” concluded Dr Olszewski and colleagues.—Alexandra Graziano
Olszewski AJ, Avigdor A, Babu S, et al. Single-Agent Mosunetuzumab Is a Promising Safe and Efficacious Chemotherapy-Free Regimen for Elderly/Unfit Patients with Previously Untreated Diffuse Large B-Cell Lymphoma. Presented at: the 62nd ASH Annual Meeting and Exposition; December 5-8, 2020; virtual. Abstract 401.
