Polivy (polatuzumab vedotin-piiq)

The patient received molecularly guided therapy with Pola-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, prednisone) plus venetoclax, achieving complete metabolic remission. Due to the persistent MEF2B and TET2 mutations in ctDNA indicated MRD positive, which prompted she received consolidative CAR-T therapy (axicabtagene ciloleucel)...The BCL2 inhibitor venetoclax has shown good therapeutic effects on DLBCL overexpressing BCL2. An integrated approach incorporating these strategies may improve outcomes for this rare lymphoma subtype.

P4, N=600, Recruiting, Henan Cancer Hospital; Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital

P1/2, N=12, Recruiting, Washington University School of Medicine | Trial completion date: May 2031 --> May 2032 | Trial primary completion date: May 2026 --> May 2027

These findings suggest that polatuzumab vedotin-induced CD20 upregulation provides a molecular rationale to explain the synergistic effect of this combination therapy. The authors have confirmed clinical trial registration is not needed for this submission.

R-CHOP remains the frontline standard, with polatuzumab-R-CHP conferring a subgroup-dependent progression-free survival gain, yet early relapse and primary refractoriness persist. On the other side, CNS risk assessment is best approached with CNS-IPI refined by site and genotype; prophylaxis remains individualized given mixed efficacy signals. Overall, risk-adapted, biologically driven care should report NCCN-IPI (alongside IPI) in all patients and incorporate imaging burden, genomics, and ctDNA where feasible.

Currently, approximately sixty percent of patients are cured with R-CHOP as frontline treatment, while the remaining patients experience primary refractory or relapsed (R/R) disease. Recently, the introduction of Pola-R-CHP as front-line therapy has represented a major advance in the management of DLBCL, resulting in improved outcomes...The most extensively studied BsAbs, in both the frontline and relapsed/refractory (R/R) settings, include epcoritamab, glofitamab, mosunetuzumab, and odronextamab...EMA has also approved glofitamab in combination with gemcitabine and oxaliplatin (GemOx) for patients with R/R DLBCL ineligible for ASCT, whereas this indication has not been approved by FDA...BsAbs represent a breakthrough therapy in the treatment of DLBCL, especially in R/R diseases. The purpose of this article is to review the landscape of BsAbs in DLBCL.

Pola plus chemotherapy demonstrates superior efficacy and may prolong survival in patients with newly diagnosed advanced or high-risk DLBCL. However, it does not mitigate the unfavorable prognosis in patients with high P53 expression.

Interestingly, 2 of the 3 CNSL patients achieved a complete response to pola-based treatment. In summary, these data indicate pola is effective against pre-clinical CNSL models and can partially penetrate the BBB in CNSL patients, which together provide support for the evaluation of pola-based treatment in future clinical trials of primary and secondary CNSL.

P2, N=20, Recruiting, Weill Medical College of Cornell University | Trial completion date: Sep 2026 --> Sep 2027 | Trial primary completion date: Sep 2025 --> Sep 2026

P1/2, N=0, Withdrawn, Karyopharm Therapeutics Inc | N=350 --> 0 | Suspended --> Withdrawn

P3, N=306, Active, not recruiting, GWT-TUD GmbH | Trial primary completion date: Dec 2026 --> Dec 2025 | Trial completion date: Dec 2027 --> Dec 2025