The DREAM-7 trial showed a belantumab combination had an overall survival benefit versus a daratumumab regimen, a "premier drug" that previously changed the myeloma treatment landscape. This surprising result establishes a new, higher standard of care and positions belantumab as a top-tier therapy, not merely another option.
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In the Cartitude 1 trial, the strongest predictor of long-term remission with Siltacel was a lower burden of disease (measured by bone marrow percentage and soluble BCMA levels), rather than the number of prior treatments. This implies using CAR-T therapy earlier in the disease course is more effective.
The field of multiple myeloma has transformed from having few treatments to an abundance of effective drugs. The primary clinical challenge is no longer finding a therapy that works, but rather determining the optimal sequence and combination of available options, highlighting a unique form of market maturity.
Clinicians must weigh the immediate benefit of using community-accessible belantumab against the risk of reducing the efficacy of future BCMA-targeted therapies like CAR-T or bispecifics. This decision hinges on a patient's ability to travel and access advanced care, creating a complex treatment sequencing challenge.
The drug's wide safety window is not just a separate benefit; it enables higher doses without toxicity. This increased dosage leads to better target coverage and potency, resulting in efficacy rates that are double the previous best. The improved safety profile is the direct cause of the enhanced efficacy.
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.
Actuate employed a master protocol that tested their drug alongside eight different standard-of-care chemotherapies in patients who had already failed them. This design efficiently demonstrated the drug's ability to reverse chemo-resistance across multiple histologies, informing their Phase 2 strategy.
The effectiveness of modern daratumab-based therapies has significantly improved patient outcomes. This positive development paradoxically made previous staging systems, founded in eras with less effective treatments, unable to accurately identify the highest-risk patients, necessitating the creation of a new prognostic model for the current era.
Immunotherapies can be effective even without causing significant tumor shrinkage. Immunocore's drug KimTrack had a low 5-7% objective response rate (ORR) but demonstrated a massive overall survival (OS) benefit, challenging the reliance on traditional chemotherapy metrics for evaluating modern cancer treatments.
The term "functional cure" is misleading and hinders progress. With one-third of heavily pretreated patients in the Cartitude 1 trial remaining disease-free for five years without maintenance, the data supports the classical definition of a "cure" used in other cancers. This semantic shift is crucial for advancing the field.
Clinical trial data shows that despite specific toxicities, antibody-drug conjugates (ADCs) can be better tolerated overall than standard chemotherapy. For example, trials for both sacituzumab govitecan and dato-DXd reported fewer patients discontinuing treatment in the ADC arm compared to the chemotherapy arm.
