Dr Siegel on the Current and Future Role of Mezigdomide in Multiple Myeloma

"As much as we have improved outcomes for patients with myeloma, there’s still a need for further improvement. We have every reason to [believe] that we’re continuing on that path, not just with mezigdomide, but with novel CAR T-cell therapies, new T-cell engagers, and all kinds of developments that [will allow] our patients to get better care, [achieve] better outcomes, and have better quality of life."

David Samuel Dicapua Siegel, MD, chief, Division of Multiple Myeloma, John Theurer Cancer Center, Hackensack University Medical Center, discusses the current and future role for mezigdomide (CC-92480) in the multiple myeloma treatment paradigm, and how this may evolve alongside the development of novel combinatorial approaches.

Preliminary findings from the phase 1/2 CA057-003 trial (NCT05372354

) demonstrated clinical activity and safety with 3 novel, all-oral, mezigdomide (CC-92480)-based triplet regimens for heavily pretreated patients with relapsed/refractory multiple myeloma. These results provide a strong rationale for further exploration of mezigdomide in combination with tazemetostat (Tazverik) and other novel agents, Siegel states. He adds that the results have bolstered enthusiasm for advancing mezigdomide combinations and incorporating the agent as a cornerstone in future myeloma management.

Mezigdomide, a thalidomide derivative, is poised to become a staple in multiple myeloma management, akin to its predecessors lenalidomide (Revlimid) and pomalidomide (Pomalyst), Siegel continues. The drug shows potential for synergy with CAR T-cell therapies, T-cell engagers, proteasome inhibitors, and other emerging agents, he notes. Given its versatility and efficacy, mezigdomide is likely to maintain relevance in the evolving treatment landscape over the next decade, even as newer therapies replace other standard treatment options, Siegel emphasizes.

Although outcomes have improved for patients with multiple myeloma, there is still a substantial need for further advancement. Continued innovation with agents like mezigdomide, alongside novel CAR T-cell therapies and bispecific T-cell engagers, is expected to improve patient outcomes, access to effective care, and quality of life, Siegel concludes.

Videos

David Samuel Dicapua Siegel, MD, discusses the current and future role for mezigdomide in the multiple myeloma treatment paradigm.

Dr Siegel on the Preliminary Use of Mezigdomide in Relapsed/Refractory Myeloma

David Samuel Dicapua Siegel, MD, chief, Division of Multiple Myeloma, John Theurer Cancer Center, Hackensack University Medical Center, discusses preliminary findings from the phase 1/2 CA057-003 trial (NCT05372354) evaluating the novel agent mezigdomide for patients with relapsed or refractory multiple myeloma.

David Samuel Dicapua Siegel, MD, discusses preliminary findings from the phase 1/2 CA057-003 trial of mezigdomide in relapsed/refractory multiple myeloma.

Dr Siegel on the Importance of Closing the Gaps in Cancer Care

David Samuel Dicapua Siegel, MD, medical oncologist, chief, Myeloma Division, John Theurer Cancer Center, Hackensack University Medical Center, discusses the importance of closing the gaps in cancer care and spreading awareness of current treatment inequities in oncology through campaigns such as World Cancer Day.


World Cancer Day is an initiative that unites the global community in their collective battle against the cancer epidemic. The platform serves to facilitate the overarching goal of preventing millions of deaths by fostering awareness about cancer. The theme for this year's World Cancer Day, “Close the Care Gap,” encapsulates the collective call for leaders to commit to and prioritize the fight against cancer. It also emphasizes the need for innovative strategies that address disparities and optimally allocate resources to 

 barriers. The focus is on ensuring that leaders comprehend the urgency of closing the care gap in oncology by confronting the root cause of inequities.

Siegel says that oncologists at Hackensack University Medical Center are fortunate to be affiliated with institutions in the New York metropolitan area, which is a highly diverse location. This location comprises a variety of ethnic groups and behavioral subsets, he elucidates. It is essential to investigate real-world experiences and outcomes in this diverse patient population to gain insights into cancer care not only at Hackensack Meridian Health but more broadly across various settings, Siegel explains.

Both regulatory bodies and the broader community must recognize the immense value of real-world data, Siegel says. The systematic collection of data across diverse populations should be a prerequisite for the incorporation of certain drugs into community practice.

Consequently, guidelines and regulations regarding how to integrate this approach into medical practices must be established, he concludes. Overall, assessing real-world outcomes with specific therapies in diverse patient populations can provide substantial insight into methods for improving the accessibility and proper implementation of these regimens.

David Samuel Dicapua Siegel, MD, discusses the importance of closing the gaps in cancer care and spreading awareness of current treatment inequities in oncology through campaigns such as World Cancer Day.

Dr Siegel on the Importance of Real-World Data in Patients With Multiple Myeloma

David Samuel Dicapua Siegel, MD, medical oncologist, chief, Myeloma Division, John Theurer Cancer Center, Hackensack University Medical Center, discusses the importance of utilizing real-world evidence when making treatment considerations, specifically in the treatment of patients with relapsed/refractory multiple myeloma, emphasizing the need for real-world investigations in this patient population.

Transitioning from clinical trials to real-world applications poses a complex challenge for patients with relapsed/refractory multiple myeloma, Siegel begins. Clinical trials are bound by strict eligibility criteria, resulting in a highly selected participant pool, Siegel says. Conversely, real-world data offer a more inclusive perspective, he states. In the realm of myeloma management, the focus has shifted toward CAR T cells and T-cell engagers, with 2 main commercially available products–idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti)–gaining prominence, Siegel explains. Notably, 

 in February 2022, both for the treatment of adult patients with relapsed/refractory multiple myeloma following 4 or more prior lines of therapy.

Real-world outcomes with ide-cel and cilta-cel echo findings from the pivotal clinical trials, affirming the remarkable efficacy of both therapies, he expands. In the real-world setting, ide-cel exhibits slightly lower effectiveness than cilta-cel, a finding which aligns with clinical trial observations, Siegel states. However, ide-cel boasts the advantages of lower toxicity and enhanced applicability vs cilta-cel, ensuring a higher likelihood of successful product manufacturing and expedited delivery to patients, he emphasizes. Siegel goes on to say that these factors are crucial for a subset of patients facing time constraints, for whom the risk of manufacturing failure or prolonged waiting periods, as seen with ide-cel, is not feasible.

Although real-world data support these observations, making direct comparisons between ide-cel and cilta-cel remains a challenge, he continues. Patients with more severe conditions tend to opt for the product with greater manufacturing reliability and shorter turnaround time, raising ongoing questions that require comprehensive exploration, Siegel concludes.

David Samuel Dicapua Siegel, MD, emphasizes the importance of real-world evidence when treating patients with relapsed/refractory multiple myeloma.

David M. Siegel, MD, PhD, chief of myeloma, John Theurer Cancer Center, professor of medicine, Hackensack Meridian Health, discusses the feasibility of using pomalidomide (Pomalyst) to treat patients with myeloma who have become refractory to lenalidomide (Revlimid).

When treating patients with myeloma, there is a traditional belief that once they become refractory to a drug, oncologists need to completely change classes of drugs for the next line of therapy—for example, going from an immunomodulatory agent to a proteasome inhibitor. A study presented at the 2018 ASH Annual Meeting challenged this dogma by assessing the efficacy of pomalidomide in patients who progressed on a lenalidomide-based regimen.

The trial suggested there was no detriment in doing this, and Siegel says the next steps are taking these patients and treating them with the commonly used regimen comprised of pomalidomide, corticosteroids, and daratumumab (Darzalex). Siegel adds that although these are early data in patients who have progressed on 1 or 2 prior lines of treatment, this is still potentially practice-changing.

David M. Siegel, MD, PhD, chief of myeloma, John Theurer Cancer Center, professor of medicine, Hackensack Meridian Health, discusses the feasibility of using pomalidomide to treat patients with myeloma who have become refractory to lenalidomide.

Dr. Siegel on Pomalidomide in Lenalidomide-Refractory Patients With Myeloma

David M. Siegel, MD, PhD, chief of myeloma, John Theurer Cancer Center, professor of medicine, Hackensack Meridian Health, discusses a trial distinguishing between classes of drugs in the treatment of patients with myeloma.

The landscape for myeloma, particularly in the relapsed/refractory setting, is crowded with several different FDA approved therapies. Siegel says these options can be divided into 3 classes: proteasome inhibitors such as bortezomib (Velcade) and carfilzomib (Kyprolis), immunomodulatory agents like lenalidomide (Lenvima) and pomalidomide (Pomalyst), and monoclonal antibodies such as elotuzumab (Empliciti) and daratumumab (Darzalex).

There is a dogma in myeloma that when a patients progresses on a certain therapy, they must then be moved onto a completely different class of drug for the next line of treatment. A study presented at the 2018 ASH Annual Meeting seemed to contradict this traditional belief. For example, a study evaluating the safety and efficacy of pomalidomide-based treatment in patients with relapsed and/or refractory multiple myeloma and first- or second-line lenalidomide failure, found that there was no drop-off in outcomes when patients switched from lenalidomide to pomalidomide.

David M. Siegel, MD, PhD, chief of myeloma, John Theurer Cancer Center, professor of medicine, Hackensack Meridian Health, discusses a trial distinguishing between classes of drugs in myeloma.

David M. Siegel, MD, PhD

Articles

Dr Siegel on the Current and Future Role of Mezigdomide in Multiple Myeloma

Dr Siegel on the Preliminary Use of Mezigdomide in Relapsed/Refractory Myeloma

Dr Siegel on the Importance of Closing the Gaps in Cancer Care

Dr Siegel on the Importance of Real-World Data in Patients With Multiple Myeloma

Dr. Siegel on Pomalidomide in Lenalidomide-Refractory Patients With Myeloma

Dr. Siegel on Distinguishing Between Classes of Drugs in Myeloma