The future of advanced prostate cancer treatment may involve combining ADCs with bispecific T-cell engagers. This strategy could use ADCs for a short duration to deliver a potent hit, followed by immunotherapy to achieve durable remission, potentially reducing toxicity and enabling earlier use.

Combining polatuzumab vedotin with bispecific antibodies appears particularly effective for patients with double-hit lymphoma. This is significant because these high-risk patients, who have poor prognoses, were notably excluded from pivotal trials like STAR GLOW, suggesting a potential new standard for this specific subgroup.

Dr. Patrick Baeuerle suggests that instead of engineering complex co-stimulatory signals into T-cell engagers, a more effective strategy is to combine them with standard-of-care treatments like chemotherapy or ADCs. This approach dramatically augments efficacy and has already prompted multiple Phase 3 trials.

Combining the ADC Loncastuximab before a bispecific antibody may lower the bispecific's toxicity, potentially through a debulking effect. This surprising finding suggests a strategy to improve the tolerability and delivery of bispecifics, especially in community settings.

In follicular lymphoma, the treatment goal is durable remission with manageable toxicity, not necessarily a cure. Therefore, clinicians frequently prefer using a bispecific antibody first, reserving the more complex and toxic CAR-T cell therapy for transformed disease or after a bispecific fails.

Not all CD20-targeting bispecifics can be combined with rituximab. Mosunetuzumab binds the same epitope, causing competition. However, glofitamab and epcoritamab bind different epitopes, allowing for logical and potentially synergistic combinations with rituximab-based regimens.

The long-standing platinum doublet backbone for frontline SCLC may soon be challenged. The high efficacy of novel agents like antibody-drug conjugates and bispecific antibodies in later lines is prompting trials that consider moving them into the first-line setting, a strategy previously considered "unthinkable."

Emerging data reveals significant synergy when combining antibody-drug conjugates (ADCs) like polatuzumab vedotin with bispecific antibodies like glofitumab. These combinations show impressive results in relapsed/refractory non-Hodgkin lymphoma, signaling a major future direction for developing more potent therapies.

Long-term follow-up from the pivotal epcoritamab trial reveals that 46% of DLBCL patients who achieve a complete remission maintain it at four years. This durability provides strong evidence that bispecific monotherapy, not just CAR-T, can be a curative treatment for a subset of patients.