Primary Results of the Health-Related Quality of Life (HRQoL) and Tolerability Assessments from the Phase I/II NP30179 Study of Glofitamab Monotherapy in Patients with Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL)
Authors: Bachy Emmanuel , Trask Peter , Morschhauser Franck , Corradini Paolo , Wu Shang-Ju , Bartlett Nancy L. , Mulvihill Estefania , Bene Tchaleu Fabiola , Lundberg Linda , Carlo-Stella Carmelo 
Published: December 2024

Background: Meaningful improvements in, or maintenance of, pre-treatment HRQoL are crucial for patients (pts) with R/R LBCL; therefore, it is important that treatments (txs) do not introduce toxicities that negatively impact pts' quality of life (QoL). Glofitamab (Glofit) is a CD20xCD3 bispecific antibody that engages and redirects T cells to eliminate B cells. Glofit monotherapy is approved in pts with R/R LBCL after ≥2 prior lines of therapy (LoT), based on data from a Phase I/II study (NP30179; NCT03075696). Results showed that fixed-duration Glofit was well tolerated and induced high complete response rates and durable responses with a manageable safety profile (Dickinson NEJM 2022; Hutchings ASH 2023). Here, we present patient-reported HRQoL and disease- and tx-related symptom data from the Phase II expansion cohorts.

Methods: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30; scale range 0-100; functional and Global Health Status/QoL scales: high score = good HRQoL; symptom scale: high score = high level of symptoms) was used to assess HRQoL, physical, social, emotional, role, cognitive functioning and tx-related symptoms; and the Functional Assessment of Cancer Therapy-Lymphoma lymphoma subscale (FACT-Lym LymS; scale range 0-60; high score = good HRQoL) assessed symptoms of lymphoma in pts with R/R LBCL (≥2 prior LoT) treated with Glofit monotherapy in the Phase II expansion cohorts. Minimally important difference cutoffs were used to determine whether cohorts exhibited meaningful change on the QLQ-C30 scale (&gt;10 points) and on the FACT-Lym LymS (≥3 points). The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was used to assess frequency, severity, interference, or presence/absence of tx-related symptoms. Symptoms were rated on a 5-point scale for each attribute. A subset of 6 symptoms (memory interference, headache, numbness and tingling, dizziness, hair loss, joint pain) deemed most applicable to the txs were selected for this study. Measures were completed on Day (D)1 of Cycles (C)1-3, 5, 7, 9, and 12 (during tx); at end of tx; and every 3 months after tx until progression. The PRO-CTCAE was also completed on C1D8, C1D15, and C2D8.

Results: As of September 2023, 155 pts were enrolled (148 pts in expansion cohorts), with a median observation time of 32.1 months (range: 0-43). Median age was 66 years (range: 21-90) and pts received a median of 3 prior LoT (range: 2-7). Questionnaire completion rates were high throughout the study (94% at baseline; &gt;88% up to C7D1; 71% at tx completion; &gt;66% through 12-month follow-up). At baseline, pts exhibited medium-high levels of HRQoL (mean QLQ-C30 Global Health Status/QoL: 56) and functioning, and low levels of disease (mean FACT-Lym LymS: 45) and tx-related symptoms. During tx, pts maintained baseline levels of HRQoL and functioning, had improvements in lymphoma-related symptoms (2-5 points) and pain (4-14 points), and no meaningful increase in tx-related symptoms. At C7D1, 84% of pts reported either clinically meaningful improvement or no change in lymphoma-related symptoms. Post-tx follow-up data showed improvements or maintenance of HRQoL, functioning, and lymphoma symptoms.

From baseline to C7D1, the majority of pts did not experience hair loss (&gt;84%), numbness/tingling of the hands and feet (&gt;71%), dizziness (&gt;79%), memory problems (&gt;74%), and headaches (&gt;55%). Equally high numbers of pts reported no diarrhea, nausea, or constipation over the study with fewer pts reporting no joint pain at baseline (37%) or up to C7D1 (33%-63%). At C7D1, the majority of pts continued to report no symptoms, although some reported worsening of hair loss (8%), numbness/tingling of the hands and feet (22%), dizziness (6%), memory problems (10%), joint pain (23%), and headaches (21%). The majority of pts (&gt;55%) reported no or improved tx-related symptoms during post-tx follow-up visits.

Conclusions: Pts treated with Glofit monotherapy experienced improvement or maintenance of HRQoL, functioning, and lymphoma symptoms during tx and follow-up. Symptoms potentially associated with Glofit, based on the PRO-CTCAE, were either not experienced or were experienced by few pts. These results suggest that Glofit monotherapy improves or maintains tx-related symptoms, and based on patient-reported outcomes, is tolerable for pts with R/R LBCL.