How Surrogate Endpoints Are Shortening Multiple Myeloma Drug Timelines

Nathan Pennell, MD, PhD, FASCO, senior vice president, head of Hematology and Oncology Medical Affairs, Bristol Myers Squibb (BMS), spoke with BioPharm International® about surrogate endpoints in multiple myeloma (MM) and the role of medical affairs in clinical strategy. Dr Pennell notes that improved MM treatments have created a development challenge. He explains that patients live longer and respond for years before resistance develops, so traditional endpoints such as progression-free survival and overall survival take a long time to read out. A highly effective drug may reach patients more slowly.

Surrogate endpoints address that delay, Dr Pennell says. Minimal residual disease (MRD)-negative complete responses are the deepest measure of response in MM. Research has established that MRD correlates with progression-free survival, and FDA now accepts it as an endpoint for accelerated approval. The first oral cereblon E3 ligase modulation (CELMoD) agent for MM has been approved on this basis, he says, and more drugs are likely to follow.

Does the MRD endpoint change how clinicians use myeloma drugs?

Dr Pennell distinguishes between an endpoint accepted for accelerated approval and what clinicians use in practice. He notes that the MRD assay is not needed to determine whether the drug is working.

"You can prescribe the drug, and you can monitor patients with whatever clinical assays you would normally use in your practice," he says.

Dr Pennell also describes how medical affairs informs trial design. For example, his group gathers patient and clinician perspectives on treatment gaps and care barriers. Where trials excluded patients, such as those with comorbidities, the group generates real-world data or evidence generation trials. He cites his work refreshing BMS's lung cancer strategy to assess unmet needs over the next decade.

About the speaker

Nathan Pennell, MD, PhD, FASCO, Senior Vice President, Head of Hematology and Oncology Medical Affairs, Bristol Myers Squibb

In his role at Bristol Myers Squibb, Dr Pennell leads medical strategy and works to translate pipeline innovation into progress for people living with cancer. He previously spent nearly 2 decades at Cleveland Clinic, directing its Lung Cancer Medical Oncology Program, serving as its vice chair of clinical research, and authoring more than 100 peer-reviewed publications in journals such as the New England Journal of Medicine, Nature, and The Lancet. Dr Pennell is a former American Society of Clinical Oncology (ASCO) board member and former editor in chief of the ASCO Educational Book.