Current fixed-duration CLL regimens are not MRD-guided, so the test result does not alter the treatment plan. While a negative result is prognostically favorable, its main clinical utility is to provide reassurance. A detectable result can cause unnecessary patient anxiety.

After observing deep, MRD-negative responses at their starting dose, Colonia Therapeutics unconventionally tested a lower dose level. This counter-intuitive strategy aims to identify the minimum effective dose, which is crucial for maximizing the safety profile (the therapeutic window) and improving commercial viability through lower manufacturing costs.

A novel trial design used mosinutuzumab monotherapy first in frontline follicular lymphoma, adding lenalidomide only for patients without a complete response. This adaptive approach successfully spared about two-thirds of patients from the added toxicities of lenalidomide while still achieving very high overall efficacy.

The failure of an adjuvant trial for the TKI pazopanib was likely caused by a protocol change that reduced the dose to manage transaminitis. While well-intentioned to improve tolerability and adherence, the lower dose was sub-therapeutic. This serves as a critical lesson that managing side effects by compromising dose can nullify a drug's potential efficacy.

The treatment backbone for Ph+ ALL is shifting away from intensive chemotherapy like hyper-CVAD. Chemotherapy-free regimens combining blinatumomab with a TKI (preferably ponatinib) are becoming the new standard, showing outcomes that are at least as good as, and likely better than, traditional chemotherapy.

Due to significant ocular toxicity affecting most patients, the approved starting dose for belantumab is likely not optimal long-term. Effective management requires clinicians to proactively hold, delay, and reduce doses at the first sign of side effects, meaning real-world application will differ from the initial protocol.

Despite the high likelihood (75%) of a T315I mutation at relapse on first or second-generation TKIs, testing is not critical for the immediate treatment decision. The most potent TKI, ponatinib, would be the next line of therapy regardless of the mutation status, making the test more of a confirmation than a decision driver.

Avapritinib is dosed at 200mg for advanced systemic mastocytosis (SM) but only 25mg for indolent SM. This tenfold difference is not based on tolerance but on the goal of therapy: extending survival in advanced SM versus improving quality of life without significant toxicity in indolent SM, where survival is near-normal.

Data on Enfortumab Vedotin suggests that for modern therapies, maintaining patients on treatment longer via a lower, more tolerable starting dose is more important than administering the maximum labeled dose upfront, a concept inherited from the cytotoxic chemotherapy era.