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.

Real-world data suggests that using one antibody-drug conjugate (ADC) immediately after another is often ineffective. A potential strategy to overcome this resistance is to administer a different class of chemotherapy before starting the second ADC.

With multiple ADCs available, an emerging sequencing strategy is to alternate between different mechanisms of action, such as following a microtubule toxin-based ADC with a topoisomerase-1 inhibitor payload. This approach aims to avoid compounding specific toxicities, like neuropathy, and potentially circumvent resistance, though it is a strategy born from logic rather than clinical trial data.

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.

To mitigate the severe toxicity of promising pan-RAS inhibitors, companies are adopting antibody-drug conjugate (ADC) technology. This marks a strategic expansion for ADCs, moving beyond traditional cytotoxic chemotherapy payloads to delivering highly specific targeted therapies, aiming to improve the therapeutic window of potent new drug classes.

An expert treating DLBCL states they no longer use bispecific antibodies as monotherapy. Combining them with partners like chemotherapy (GemOx) or ADCs (Polatuzumab) raises the complete response rate by 15-20%, offering a better chance of benefit for patients.

As multiple effective Antibody-Drug Conjugates (ADCs) become available, the primary clinical challenge is no longer *if* they work, but *how* to use them best. Key unanswered questions involve optimal sequencing, dosing for treatment versus maintenance, and overall length of therapy, mirroring issues already seen in breast cancer.

A key principle for clinicians is that an antibody-drug conjugate's adverse events are primarily dictated by its linker-payload (e.g., deruxtecan, vedotin), not its specific antibody target. This allows for anticipating toxicities like neuropathy or GI issues based on the payload class, creating a predictable framework for management across different ADCs.