Editor's Note: In 2025, the International Conference on Malignant Lymphoma (ICML) brought together top global hematologic oncology experts to discuss the latest advancements and future trends in lymphoma treatment. During the Late-Breaking Abstract (LBA) session at this conference, Professor Jason Weston from MD Anderson presented a report titled "Mosunetuzumab Combined with Polatuzumab Vedotin Shows Superior Efficacy to R-GEMOX in Transplant-Ineligible Relapsed/Refractory Large B-Cell Lymphoma Patients: Primary Results of the Phase III SUNMO Study." This study presented the preliminary analysis results of the SUNMO Phase III clinical trial for the first time, demonstrating an innovative, fixed-duration, chemotherapy-free regimen that achieved significantly superior efficacy compared to the traditional R-GEMOX regimen in treating relapsed/refractory large B-cell lymphoma (R/R LBCL), with a favorable safety profile, bringing new hope to this patient population.Treatment Dilemmas and the Emergence of Innovative Solutions
For patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) who are ineligible for curative treatments such as autologous stem cell transplantation or chimeric antigen receptor T-cell (CAR-T-cell) therapy, the prognosis is often poor. Numerous factors limit these patients’ access to curative treatments, including lack of response to previous therapies, age, frailty, and toxicities associated with T-cell-redirecting therapies such such as cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). These toxicities not only restrict treatment opportunities but also increase the burden on the healthcare system. Against this backdrop, two innovative drugs have emerged: Mosunetuzumab, a T-cell bispecific antibody that mediates T-cell killing of tumor cells by simultaneously targeting CD20 and CD3; and Polatuzumab Vedotin, an antibody-drug conjugate (ADC) that targets CD79b. A previous Phase II study had confirmed the MosunPola (Mosunetuzumab combined with Polatuzumab Vedotin) regimen as an outpatient treatment, demonstrating durable efficacy and a favorable safety profile. Based on these encouraging early data, the global Phase III SUNMO clinical trial was initiated to further evaluate the efficacy and safety of the MosunPola regimen versus the R-GEMOX (rituximab, gemcitabine, oxaliplatin, and dexamethasone) regimen in transplant-ineligible R/R LBCL patients.
SUNMO Phase III Study Design and Patient Characteristics
The SUNMO study enrolled R/R LBCL patients who had received at least one prior line of therapy and were ineligible for autologous stem cell transplantation, including transformed follicular lymphoma, high-grade B-cell lymphoma, and Grade 3b follicular lymphoma. Patients were randomized 2:1 to receive either fixed-duration MosunPola regimen (as an outpatient treatment) or R-GEMOX regimen. Mosunetuzumab was administered subcutaneously for 8 cycles, with dose escalation in Cycle 1; Polatuzumab Vedotin was administered intravenously for 6 cycles, every 21 days. The control R-GEMOX regimen was administered intravenously every 14 days for 8 cycles, but cycles could be extended to 21 days if hematologic toxicity occurred.
The SUNMO study had dual primary endpoints: overall response rate (ORR) and progression-free survival (PFS) as assessed by an independent central review committee. Secondary endpoints included overall survival (OS). The study commenced in April 2022, and a prespecified interim analysis conducted in April 2024 found that the interim ORR had reached the statistical significance threshold, prompting the independent data monitoring committee to recommend early cessation of patient enrollment. A total of 208 patients were ultimately enrolled (originally planned for 222 patients). The primary PFS analysis was completed in February 2025, with a median follow-up of 23.2 months, and an interim OS analysis was also performed.
Patient baseline characteristics were generally balanced between the two groups. Notably, the MosunPola group had a slightly higher proportion of patients with ECOG performance status score of 2 and bulky disease, both of which are known poor prognostic factors. The median number of prior lines of therapy was 2, with approximately 43% of patients having received only one prior line of therapy, and about 60% of patients being refractory to their initial treatment regimen.
MosunPola’s Excellent Efficacy Data: PFS and ORR Double Breakthrough
The SUNMO study results showed that the MosunPola regimen significantly extended patients’ progression-free survival (PFS) and improved overall response rate (ORR), achieving both dual primary endpoints.
In terms of PFS, the median PFS in the MosunPola group was 11.5 months, significantly superior to 3.8 months in the R-GEMOX group, with a hazard ratio (HR) of 0.41 and a p-value of less than 0.0001. This means the MosunPola regimen extended median PFS by more than three times. At 12 months, the PFS rate in the MosunPola group was 48.5%, compared to 17.8% in the R-GEMOX group, with MosunPola reducing the risk of disease progression or death by 59%. In exploratory subgroup analyses, the MosunPola regimen demonstrated a consistent trend of PFS improvement across all key subgroups (including age, cell of origin, and geographic region) and also performed well in stratified factor subgroups (number of prior lines of therapy and refractory disease status). Regarding ORR, the ORR in the MosunPola group was as high as 70.3%, while that in the R-GEMOX group was 40.0%, an absolute difference of 30.3%, which was highly statistically significant. More encouragingly, the complete response (CR) rate in the MosunPola group reached 51.4%, more than double the 24.3% in the R-GEMOX group. Furthermore, the durability of CR with the MosunPola regimen was also better. At 12 months, 73% of patients who achieved CR in the MosunPola group remained in ongoing remission, compared to only 44% in the R-GEMOX group. This means that nearly three-quarters of CR patients in the MosunPola group were still in remission after one year, while less than half in the R-GEMOX group. Interim analysis of overall survival (OS) showed a median OS of 18.7 months in the MosunPola group and 13.6 months in the R-GEMOX group, with a hazard ratio (HR) of 0.8. Although the current confidence interval extends beyond 1, OS was numerically prolonged, and at 12 months, the patient survival rate in the MosunPola group was 61%, higher than 53% in the R-GEMOX group. The final statistical analysis for OS has not yet been performed, as the number of death events in the study is currently insufficient for a definitive assessment.
Safety and Tolerability: Significant Advantages of Non-Chemotherapy Regimens
Despite patients in the MosunPola group receiving more cycles of treatment (median 8 cycles vs. median 5 cycles in the R-GEMOX group), the overall incidence of adverse events (AEs) was similar between the two groups, and treatment-related fatal AEs were very rare in both groups. The proportion of patients discontinuing MosunPola due to AEs was 2%, lower than 4.7% in the R-GEMOX group.
Overall, the safety profile of the MosunPola regimen was consistent with the known risk characteristics of the individual drugs, and no new synergistic toxicities were observed. More common toxicities in the MosunPola group included injection site reactions and cytokine release syndrome (CRS), while thrombocytopenia, neutropenia, anemia, nausea, diarrhea, and peripheral neuropathy were more common in the R-GEMOX group.
Notably, CRS induced by the MosunPola regimen was generally low-grade and occurred early. The incidence of any-grade CRS was 25.9%, but Grade ≥2 CRS was only 4.4%, with Grade 1 CRS (fever only) accounting for 21.5%. This means that 96% of patients treated with MosunPola did not experience significant CRS. Only 4.4% of patients required tocilizumab for CRS, and 3.7% required corticosteroids. Furthermore, the incidence of CRS was predictable, with almost all events occurring within the first cycle. Although injection site reactions were common, ICANS was not observed in the SUNMO trial. Peripheral neuropathy occurred almost twice as frequently in the R-GEMOX group as in the MosunPola group, while the incidence of febrile neutropenia was very low in both groups.
Expert Insights and Future Outlook
Professor Jason Weston concluded that SUNMO is the first Phase III study of a non-traditional chemotherapy regimen to achieve positive results in second-line or later transplant-ineligible diffuse large B-cell lymphoma patients. The MosunPola regimen reduced the risk of disease progression or death by 59%, extended median progression-free survival by three-fold, and doubled the complete response rate. Its incidence and severity of CRS were among the lowest reported for T-cell-redirecting therapies to date, with 96% of patients experiencing no significant CRS. These advantages are expected to expand patient access to highly effective treatment and support widespread outpatient application in more treatment centers. In the subsequent Q&A session, Professor Jason Weston offered insights into the comparison of the MosunPola regimen with other innovative therapies (such as Glofitamab-GEMOX, Pola-R-GEMOX). He noted that direct comparisons are difficult due to differences in study populations, but the SunMo study allowed the inclusion of high-grade B-cell lymphoma patients, and the R-GEMOX group’s dosing frequency was every 14 days, which differs from other studies. He emphasized that having multiple effective treatment options is a huge advancement for patients. Professor Jason Weston also specifically pointed out that MosunPola, as a regimen without conventional chemotherapy, offers advantages in terms of safety, which may make it more suitable for use in community practices beyond academic centers. Regarding whether patients had received prior Polatuzumab or CAR-T-cell therapy, Professor Jason Weston explained that the SUNMO study began in 2022, when Polatuzumab was not widely adopted as a first-line standard of care. The study allowed patients who had previously received Polatuzumab and achieved durable remission for more than one year to be enrolled, but such patients were very few. Furthermore, less than 10% of patients had previously received CAR-T-cell therapy. For younger patients ineligible for transplant, he explained that the most common reasons include age, no response to previous chemotherapy, and frailty. Professor Jason Weston concluded by expressing his anticipation for more mature overall survival data in the future, which will further clarify the long-term benefits of the MosunPola regimen. The success of the SUNMO study not only provides new chemotherapy-free treatment options for R/R LBCL patients but also sets a new milestone in the development of lymphoma immunotherapy. This fixed-duration outpatient regimen, combining the advantages of bispecific antibodies and antibody-drug conjugates, has demonstrated excellent performance in both efficacy and safety, heralding a significant transformation in lymphoma treatment paradigms.
Contributor/Interview Source: Oncology Outlook – Oncology News
