Prognosis for patients with refractory/relapsed large B-cell lymphoma (LBCL) considered ineligible for curative-intent therapy is poor. The combination of mosunetuzumab, a T-cell–engaging bispecific antibody, and polatuzumab vedotin, an antibody-drug conjugate (Mosun-Pola), represents a novel fixed-duration outpatient therapy.
In the phase III SUNMO trial, patients with refractory/relapsed LBCL who were ineligible for autologous stem-cell transplant were randomly assigned (2:1) to receive Mosun-Pola or rituximab, gemcitabine, and oxaliplatin (R-GemOx). Dual primary end points were centrally assessed overall response rate (ORR) and progression-free survival (PFS). Overall survival was a key secondary end point.
A total of 208 patients were randomly assigned to receive Mosun-Pola (n = 138) or R-GemOx (n = 70). a median follow-up of 23.2 months, the primary analysis of SUNMO demonstrated that the median PFS was significantly longer with Mosun-Pola than with R-GemOx (11.5 months [95% CI, 5.6 to 18] v 3.8 months [95% CI, 2.9 to 4.1]; hazard ratio for progression or death, 0.41 [95% CI, 0.3 to 0.6]; P < .0001). ORR was significantly greater with Mosun-Pola versus R-GemOx (70% v 40%; P < .0001), with complete response rates of 51% and 24%, respectively. In the Mosun-Pola group, the rate of grade ≥2 cytokine release syndrome (CRS) and usage of tocilizumab occurred in
Mosun-Pola demonstrated superior efficacy versus R-GemOx, with significant improvements in both ORR and PFS, and infrequent CRS events with a manageable safety profile.
Another update demonstrated the superiority of polatuzumab vedotin plus R-CHOP (Pola-R-CHOP) over R-CHOP alone, with improved progression-free survival (PFS) (64% vs 59%). Overall survival (OS) was not statistically significant; however, the hazard ratio was 0.85, with greater benefit observed in high-risk patients.
Minimal residual disease (MRD) testing after two cycles of therapy and at the end of treatment predicted 2-year progression-free survival (PFS) (96% in MRD-negative patients vs 67% in MRD-positive patients). MRD status was more predictive of treatment outcomes than radiographic imaging in this patient population.
The EPCORE NHL-2 phase 1b/2 trial evaluated fixed-duration epcoritamab plus R2 in R/R FL after at least one prior line, showing impressive efficacy with an overall response rate (ORR) of 96% and a complete response (CR) of 88%, and 2-year rates for remaining in CR (82%), progression-free survival (PFS) (76%), overall survival (OS) (90%), and freedom from next therapy (84%)—all with non-reached medians. High-risk groups did just as well, with CR rates of 90% in primary refractory, 82% in double refractory. MRD negativity was achieved by 86% overall. Safety was manageable, with mostly low-grade CRS (grade 1/2/3: 38%/11%/2%), neutropenia (65%), and COVID-19 (59%)—notably, no CRS-related discontinuations. This chemo-free, off-the-shelf regimen is delivering deep, durable remissions with practical outpatient dosing—something we’ve all been hoping to see for R/R FL.
The phase 2 trial of Moga-CHOP (CHOP + mogamulizumab) in older patients with aggressive adult T-cell leukemia/lymphoma (ATL) demonstrated a significant improvement in 1-year PFS (36.2% vs 16% historical control), with a 1-year OS of 66.0% and a CR rate of 64.6%. The overall response rate (ORR) was high at 91.7%, and the median overall survival (OS) reached 1.6 years. Notably, CCR4 mutations and Moga-associated cutaneous AEs correlated with better OS, and the regimen was generally tolerable with no unexpected toxicities. Bottom line: Moga-CHOP is now a strong first-line option for older, transplant-ineligible ATL patients, and it’s encouraging to see these survival gains in a population with historically poor outcomes.
Pirtobrutinib improved progression-free survival (PFS) to 14 months compared to 8 months with Idelalisib/Rituximab or Bendamustine/Rituximab (IdelaR/BR), with a hazard ratio of 0.54, in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had previously been treated with covalent BTK inhibitors (cBTKi). It also demonstrated favorable tolerability. With acalabrutinib and venetoclax emerging as preferred first-line therapies, Pirtobrutinib represents a strong second-line option for eligible patients.