SYED A. ABUTALIB, MD
In an effort to help clinicians stay current with rapidly evolving hematology-oncology literature, we are providing these concise, clinically focused summaries of important peer-reviewed studies. These summaries are intended to highlight key findings, study design, and outcomes that may inform clinical practice.
This feature is not a substitute for full manuscript review. Readers are encouraged to consult the original publications for a comprehensive understanding of study methodology, detailed subgroup analyses, and full safety data. Full sourcing to the original articles is provided.
SUNMO Trial: Mosunetuzumab Plus Polatuzumab Vedotin in R/R Large B-Cell Lymphoma
The phase III SUNMO trial evaluated the combination of the bispecific CD20-directed CD3 T-cell engager mosunetuzumab and the antibody-drug conjugate (CD79b) polatuzumab vedotin (Mosun-Pola) in patients with relapsed/refractory large B-cell lymphoma (LBCL) who were ineligible for autologous stem-cell transplant.1 This population of patients with relapsed/refractory LBCL considered ineligible for curative-intent therapy represents a group with limited treatment options; according to researchers, such patients face poor outcomes with palliative therapies.
In this global, randomized study conducted across 50 sites in 13 countries, 208 patients were assigned in a 2:1 ratio to receive Mosun-Pola (n = 138) or the standard regimen of rituximab/gemcitabine/oxaliplatin (R-GemOx; n = 70). Eligible patients had histologically confirmed LBCL and had relapsed after at least one prior therapy. The dual primary endpoints were overall response rate and progression-free survival, with overall survival as a key secondary endpoint.
At a median follow-up of 23.2 months, Mosun-Pola demonstrated significantly improved efficacy compared with R-GemOx. Median progression-free survival was 11.5 months in the Mosun-Pola group vs 3.8 months in the control arm (hazard ratio [HR] 0.41; P < .0001). The overall response rate was also higher with Mosun-Pola (70% vs 40%; P < .0001), with complete response rates of 51% compared with 24% in the R-GemOx group.
The study reports median overall survival of approximately 19 months with Mosun-Pola vs 14 months with R-GemOx, with a hazard ratio of 0.80 (P = .28). The safety profile of Mosun-Pola was described as manageable. Rates of grade 2 or higher cytokine release syndrome occurred in fewer than 5% of patients, and the use of the interleukin-6 receptor antagonist tocilizumab was similarly infrequent. Patient-reported outcomes were improved with Mosun-Pola relative to R-GemOx.
The rationale for combining mosunetuzumab, a CD20 x CD3 bispecific antibody, with polatuzumab vedotin, a CD79b-directed antibody-drug conjugate, is supported by complementary mechanisms of action, including T-cell engagement and enhanced cytotoxicity. Both agents had previously demonstrated activity in relapsed or refractory LBCL, and their combination was designed to provide a fixed-duration, outpatient treatment option.
Overall, the SUNMO trial demonstrated that Mosun-Pola significantly improved response rates and progression-free survival compared with a widely used standard regimen, with a tolerable safety profile in a transplant-ineligible population.
CARTITUDE-4: Ciltacabtagene Autoleucel in Lenalidomide-Refractory Myeloma
The CARTITUDE-4 trial is a randomized, open-label, phase III study evaluating ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, in patients with lenalidomide-refractory multiple myeloma who had received one to three prior lines of therapy.2
A total of 419 patients were randomized to receive either a single infusion of cilta-cel (n = 208) or standard-of-care therapy (n = 211), consisting of physician’s choice of pomalidomide/bortezomib/dexamethasone or daratumumab/pomalidomide/ dexamethasone. The primary endpoint was progression-free survival; this report presents a prespecified interim analysis of overall survival along with updated efficacy and safety outcomes.
At a median follow-up of 33.6 months, progression-free survival was not reached in the cilta-cel group compared with 11.8 months in the standard-of-care group (HR 0.29; 95% CI 0.22–0.39). Overall survival was also improved with cilta-cel, with the median not reached in either group but a hazard ratio of 0.55 (95% CI 0.39–0.79; P = .0009), indicating a significant reduction in the risk of death.
Safety figures are based on the safety population, not the full randomized population. This included 208 patients for the cilta-cel group and 208 for the standard-of-care group who were included in the safety analysis for these adverse-event comparisons.
Adverse events were common in both groups. Maximum grade 3 treatment-emergent adverse events occurred in 14% of patients receiving cilta-cel and 37% in the standard-of-care group. Maximum grade 4 events occurred in 75% and 56% of patients, respectively, most commonly neutropenia. Serious adverse events were reported in 47% of patients in both groups.
Deaths occurred in 24% of patients in the cilta-cel group and 39% in the standard-of-care group. Treatment-related deaths were reported in 3% and 2% of patients, respectively, most often due to infection.
CARTITUDE-4 builds on prior analyses demonstrating improved progression-free survival with cilta-cel and now shows a significant overall survival benefit. These findings support the use of cilta-cel earlier in the treatment course for patients with lenalidomide-refractory disease.
QUIWI Trial: Quizartinib in Newly Diagnosed FLT3-ITD–Negative AML
The phase II QUIWI trial evaluated the addition of quizartinib, an oral, selective FLT3 inhibitor, to standard induction and consolidation chemotherapy in patients aged 18 to 70 years with newly diagnosed FLT3-ITD–negative acute myeloid leukemia (AML).
In this randomized, double-blind, placebo-controlled study, 273 patients were assigned in a 2:1 ratio to receive quizartinib (n = 180) or placebo (n = 93), in combination with standard chemotherapy, followed by single-agent maintenance therapy with the assigned agent. Allogeneic transplant was allowed when indicated. The primary endpoint was event-free survival, with overall survival and safety as secondary endpoints.
At the time of data cutoff, median event-free survival was 20.4 months in the quizartinib arm compared with 9.9 months in the placebo arm (P = .046). Median overall survival was not reached in the quizartinib group and was 29.3 months in the placebo group (P = .012). The 3-year overall survival rates were 60.8% for quizartinib and 45.7% for placebo.
The most frequently reported adverse events of any grade included fever, rash, diarrhea, and mucositis. The study demonstrated that adding quizartinib to standard chemotherapy significantly improved both event-free and overall survival in this patient population.
FLT3 mutations are present in approximately one-third of patients with AML; however, therapeutic strategies targeting FLT3 in FLT3-ITD–negative disease have been less well established. Quizartinib has shown activity against both mutant and wild-type FLT3, providing a rationale for its evaluation in this setting.
The QUIWI trial provides evidence that incorporation of quizartinib into standard treatment may improve outcomes even in patients without FLT3-ITD mutations.
Conclusion
Across these three studies, several common themes emerge. Each trial evaluates a targeted or immunotherapy-based approach added to or replacing existing standards of care in hematologic malignancies. In all cases, these strategies were associated with improvements in key efficacy endpoints, including progression-free survival, event-free survival, or overall survival.
Additionally, these studies reflect an ongoing shift toward more precise and mechanism-driven therapies, including bispecific antibodies, CAR T-cell therapy, and targeted kinase inhibition. Despite differences in disease settings and treatment modalities, all three trials demonstrate that novel agents can improve outcomes in populations with historically limited treatment options.
Taken together, these findings underscore the continued evolution of hematologic oncology toward more targeted and effective therapeutic approaches, while reinforcing the importance of carefully evaluating safety profiles alongside clinical benefit.
DISCLOSURE: For full disclosures of all study authors, visit the original sources at the Journal of Clinical Oncology and/or The Lancet Oncology.
REFERENCES
1. Budde LE, Zhang H, Kim WS, et al: Mosunetuzumab plus polatuzumab vedotin in transplant-ineligible refractory/relapsed large B-cell lymphoma: Primary results of the phase III SUNMO trial. J Clin Oncol 43:3799-3811, 2025.
2. Einsele H, San-Miguel J, Dhakal B, et al: Ciltacabtagene autoleucel in lenalidomide-refractory multiple myeloma (CARTITUDE-4): updated analysis including overall survival. Lancet Oncol 27:254–268, 2026.
3. Montesinos P, Rodríguez-Veiga R, Bergua JM, et al: Quizartinib for newly diagnosed FLT3-ITD–negative AML: The randomized phase II QUIWI study. J Clin Oncol 44:42-52, 2026.
Dr. Abutalib is Director of the Hematologic Malignancies, Hematopoietic Stem Cell Transplantation & Cellular Therapy Program at the Aurora St. Luke’s Medical Center, Milwaukee, Wisconsin.
