Experts anticipate trials that use ctDNA to detect minimal residual disease (MRD) after standard frontline DLBCL therapy. Patients who remain MRD-positive could then be escalated to consolidation therapy with CAR T-cells, potentially improving long-term outcomes for high-risk individuals.
For CLL patients with bulky adenopathy, clinicians can delay initiating the venetoclax component of a combination therapy. Starting with the BTK inhibitor alone first debulks the tumor, making the subsequent addition of venetoclax safer by decreasing the risk of tumor lysis syndrome.
Data from the BRUIN CLL-322 trial shows that adding pirtobrutinib to venetoclax-rituximab (PVR) significantly improves progression-free survival for CLL patients who have previously been treated with a BTK inhibitor. This establishes the triplet as a new, potent, and likely future standard regimen for this high-need population.
To maximize the effectiveness of CD19-directed CAR-T therapy (Lysocel) in CLL, patients should be referred while still responding to their latest line of salvage therapy, such as pirtobrutinib. This approach leverages less-exhausted T-cells and real-world data shows it leads to higher complete remission rates.
BTK degraders work differently from inhibitors. They tag the entire BTK molecule for destruction, which is crucial because even with "kinase dead" mutations that confer resistance to inhibitors, the BTK protein's scaffolding structure remains vital for tumor signaling. This mechanism explains their high efficacy in heavily pre-treated patients.
Early trial data for single-agent bispecific antibodies in elderly or frail patients with large cell lymphoma reveals surprisingly high efficacy. This success is prompting discussions about a chemotherapy-free future for this population, with combinations like glofitumab-polatuzumab potentially replacing traditional regimens.
In clinical practice for relapsed large cell lymphoma, glofitumab is a preferred bispecific antibody. Clinicians favor it over epcoritamab because it is time-limited (vs. indefinite treatment) and has a more patient-friendly every-three-week schedule, while also being more active than mosunetuzumab.
For relapsed mantle cell lymphoma, the mosunetuzumab-polatuzumab (MOSEN-POLA) combination shows efficacy comparable to single-agent glofitumab. However, MOSEN-POLA has a significantly better safety profile with much lower rates of severe cytokine release syndrome (CRS), making it an attractive and more manageable option.
Epcoritamab combined with lenalidomide and rituximab (EPCO R-squared) is now considered the preferred second-line regimen for most follicular lymphoma patients. It has demonstrated superior efficacy compared to the tafasitamab plus R-squared regimen, effectively 'knocking it off its perch' as the standard in this setting.
Early phase 1 data for the novel CD19xCD3 bispecific antibody surorituximab (cervatamig) combined with rituximab shows unprecedented efficacy in frontline follicular lymphoma, with complete response rates approaching 100%. These impressive results have prompted an aggressive global phase 3 development strategy.