Corvus Pharmaceuticals is already planning frontline combination trials for its T-cell lymphoma drug. The drug's favorable safety profile is the critical enabler, allowing it to be paired with chemotherapy and used as a long-term maintenance therapy to prolong remissions—a strategy unavailable to more toxic drugs.

With highly effective CLL therapies, primary causes of mortality are now infections and secondary cancers from immunodeficiency. Research is now focusing on immune reconstitution after treatment, marking a pivotal shift towards managing long-term survivorship challenges beyond just controlling the leukemia itself.

When debating immunotherapy risks, clinicians separate manageable side effects from truly life-altering events. Hypothyroidism requiring a daily pill is deemed acceptable, whereas toxicities like diabetes or myocarditis (each ~1% risk) are viewed as major concerns that heavily weigh on the risk-benefit scale for early-stage disease.

To combat the significant myelosuppression from the standard 28-day venetoclax cycle in AML, many clinicians are adopting a strategy of performing a bone marrow biopsy around day 21 and pausing the drug if blast clearance is achieved to allow for hematologic recovery.

While these drugs can cause neutropenia, it rarely leads to infections. Patients often feel clinically well despite low neutrophil counts. This 'paper problem' can usually be managed with G-CSF without needing to dose-reduce the primary CLL therapy.

Unlike older IMiDs where T-cell effects are secondary, CELMoDs have a powerful, independent pro-T-cell mechanism. This dual action is so significant that in the future, CELMoDs will be prescribed not just for their direct anti-myeloma effects, but specifically to enhance the efficacy of T-cell therapies like CAR-T and bispecific antibodies.

An expert who initially viewed CELMoDs as incremental improvements now considers them fundamentally different. The new litmus test for future myeloma trials will be tracking prior patient exposure to CELMoDs like iberdomide, just as they track prior IMiD exposure today, cementing their status as a distinct therapeutic category.

While avoiding severe toxicities of older IL-2 drugs, Synthakyne's therapy causes a manageable rash. The company views this as a favorable, on-target effect, indicating the drug is successfully activating the immune system as intended, rather than as a problematic side effect.

Perioperative enfortumab vedotin-pembrolizumab (EV-Pembro) is surprisingly well-tolerated on a per-cycle basis compared to the traditional GEMSYS chemotherapy regimen. This challenges preconceived notions about the toxicity of this powerful combination, though cumulative toxicity over longer durations remains a key factor.