Treatment depends upon various factors, including the type of cancer, the stage of cancer, overall patient health, other comorbidities, and patient preferences, and therapy should be individualized to patient needs. The duration of treatment also depends upon patient factors, and often, a combination of therapies may be warranted to achieve optimal therapeutic responses. Additionally, changes in treatment may be warranted depending on patient responses to selected therapy and the incidence and severity of adverse effects. Patients may also require nutritional guidance from dieticians, nutritionists, and psychological support as part of the overall therapy plan.
Since some types of blood cancers are more aggressive and can be resistant to conventional therapies, a combination of treatments or more intensive therapies may be required. For example, diffuse large B-cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin lymphoma, and according to the Leukemia & Lymphoma Society, while this form of blood cancer is typically responsive to frontline treatment, an estimated 40% of patients will experience relapse or refractory disease for which treatment options are limited, highlighting the need for more innovative therapies.
In June 2023, the FDA approved Columvi (glofitamab-gxbm) for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma after two or more lines of systemic therapy. This indication was approved under accelerated approval based on response rate and durability of response in the phase I/II NP30179 study, and the approval marked the first and only CD20xCD3 T-cell–engaging bispecific antibody for treating R/R DLBCL that is administered for a defined period.
In the phase I/II NP30179 study, Columvi was administered as a fixed course for 8.5 months in 132 patients with DLBCL who had relapsed or were refractory to prior therapies, including about one-third (30%) who had received prior chimeric antigen receptor T-cell therapy. Additionally, 83% were refractory to their most recent therapy. Results demonstrated patients treated with fixed-duration Columvi achieved durable remission, with 56% of patients achieving an overall response (OR; 74/132 [95% confidence interval (CI): 47-65]) and 43% of patients achieving a complete response (CR; 57/132 [95% CI: 35-52]). Over two-thirds of those who responded continued to respond for at least 9 months (68.5% [95% CI: 56.7-80.3]). The median duration of response was 1.5 years (18.4 months [95% CI: 11.4-not estimable]).
In the study involving 145 patients treated with Columvi, the most common adverse events (AEs) included cytokine release syndrome (CRS; 70%), musculoskeletal pain (21%), fatigue (20%), and rash (20%). CRS, which can be serious or life-threatening, was commonly low grade, with 52% and 14% experiencing Grade 1 and Grade 2, respectively.
Contrasting treat-to-progression approaches where treatment is administered indefinitely until cancer progresses or the therapy cannot be tolerated, Columvi is administered in 13 intravenous infusions over a maximum of 12 cycles (including step-up dosing) or until disease progression or the treatment cannot be tolerated, whichever occurs first. Additionally, Columvi is a chemotherapy-free treatment option that is off-the-shelf and ready for infusion. Patients are pretreated with a single dose of obinutuzumab 7 days before initiating Columvi and are also administered a corticosteroid, an antipyretic, and an antihistamine as premedications to diminish the risk of CRS.
In June 2024, statistically significant and clinically meaningful results emerged from STARGLO, a phase III, multicenter, open-label, randomized study of Columvi (glofitamab-gxbm) in combination with chemotherapy regimens or combination chemotherapy and monoclonal antibody regimen as designated by trial researchers. Data demonstrated that the study met its primary endpoint of overall survival with a 41% reduction in the risk of death in patients with R/R DLBCL treated with Columvi plus chemotherapy.
The Columvi combination also met its key secondary endpoints, with a 63% reduction in the risk of disease worsening or death. A follow-up analysis was conducted after all patients had completed therapy (median follow-up of 20.7 months) showed continued benefit in both primary and secondary endpoints. Median overall survival for patients treated with the Columvi combination was 25.5 months, nearly double what was observed with other regimens (reported as 12.9 months), and more than twice as many patients experienced a complete response (58.5% vs. 25.3%, respectively).
Adverse event (AE) rates were higher with the Columvi combination versus the monoclonal antibody and chemotherapy regimens, noting the higher median number of cycles received with the Columvi combination (11 vs. 4). One of the most common AEs was cytokine release syndrome, which was generally low grade (Any Grade: 44.2%, Grade 1: 31.4%, Grade 2: 10.5%, Grade 3: 2.3%) and occurred primarily in Cycle 1.
Results from the STARGLO study will be submitted to global health authorities, including the FDA and the European Medicines Agency. Columvi is also being investigated in other aggressive, hard-to-treat lymphomas and was recently granted Breakthrough Therapy Designation by the FDA for the treatment of adult patients with relapsed or refractory mantle cell lymphoma who have received at least two prior therapies based on results from the phase I/II NP30179 study.
Advancements in blood cancer treatment, such as bispecific antibody therapy, targeted therapies, immunotherapies, and combination treatments, have meaningfully enhanced clinical outcomes and overall survival rates. Enhanced diagnostic techniques and clinical data highlighting the pivotal role of supportive care in cancer treatments have also improved the overall health-related quality of life for many patients.
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