New All-Oral Triplet for Older Myeloma Patients on the Horizon

Posted: Sep 24, 2024

For multiple myeloma patients over the age of 65 and those who struggle with a high risk of falls, hospital admissions, or the need for long-term care, effective treatments that are easily administered can significantly improve quality of life. This is why it is important to research new, easily administered treatments that promise better outcomes.

Treatments like the triplet combinations of daratumumab, lenalidomide, and dexamethasone (DRd) or bortezomib, lenalidomide, and dexamethasone (VRd) are commonly used in newly diagnosed myeloma patients who cannot receive a transplant. Some patients may develop resistance to these therapies after their first relapse, making it difficult to select the next treatment option. This challenge is particularly significant for those who are refractory (unresponsive) to lenalidomide and daratumumab.

In response to these challenges, an all-oral triplet combination involving iberdomide, ixazomib, and dexamethasone is currently in a phase II study. This combination is administered orally (via mouth), making it a better option for patients who may struggle with frequent hospital visits and more intensive therapies. You can read more about this study and the benefits of its design below.

What Are the Benefits of All-Oral Treatments?

Convenience and quality of life: Oral treatments allow patients to manage their therapy from the comfort of their homes, reducing the need for hospital visits. This is an advantage for elderly patients who may face mobility issues or live far from treatment centers.
Fewer hospital-based infections: By reducing the intravenous or subcutaneous therapies, patients are less exposed to potential infections, which can be a serious concern for patients with a weakened immune system.
Consistency in dosing: Oral therapies help maintain consistent drug levels in the body, which may improve treatment outcomes in some cases. This also empowers patients to adhere to their treatment plans more effectively.

What is the Iberdomide-Ixazomib-Dexamethasone Study?

A phase II study led by the Intergroupe Francophone du Myélome (IFM) focused on testing the safety and effectiveness of the oral combination of iberdomide, ixazomib, and dexamethasone (referred to as I2D) in patients aged over 70 years who had experienced a first relapse of multiple myeloma.

Treatment Regimen

Iberdomide: 1.6 mg (oral) on days 1 to 21 of a 28-day cycle.
Ixazomib: 3 mg (oral) on days 1, 8, and 15 of each cycle.
Dexamethasone: Initially 20 mg (oral) on days 1, 8, 15, and 22 during the first two cycles, and then 10 mg for subsequent cycles.

Patients received this regimen until their disease progressed or they experienced intolerable side effects.

The primary goal of the study was to determine the percentage of patients who achieved a very good partial response (VGPR) or better on this therapy combination.

Who Participated in the Study?

The study enrolled 70 patients between December 2021 and May 2023.

The participants were older adults more prone to adverse events such as falls, disability, hospital admission, or the need for long-term care. The median age was 76, and half of them had a frailty score above 2, as per the International Myeloma Working Group (IMWG) standards.

What are the Study Results?

After a median follow-up of 12 months, the key findings were as follows:

Overall response rate (ORR): 64% overall, with 33% of patients achieving VGPR.
Progression-free survival (PFS): Median PFS was 13 months
Overall Survival (OS): 12-month overall survival (OS) rate of 85%.
Refractory multiple myeloma patients: In refractory patients to both lenalidomide and daratumumab, the median progression-free survival was 10 months, showcasing the potential of iberdomide, ixazomib, and dexamethasone even in patients whose myeloma didn’t respond to previous therapies.

How Safe is this Combination?

The combination of iberdomide, ixazomib, and dexamethasone was generally well-tolerated. The most common side effects included:

Infections: Occurred in 30% of patients, but most were mild.
Peripheral neuropathy: Affected 20% of patients.
Diarrhea: Reported in 19% of patients.

Severe side effects (Grade 3-4) were: low neutrophil counts (neutropenia) (46%), low platelet counts (thrombocytopenia) (9%), and infections (8%). Four patients discontinued treatment due to side effects, including low blood cell counts (cytopenia) and skin rash.

Conclusion

The phase II study of iberdomide, ixazomib, and dexamethasone in elderly multiple myeloma patients at first relapse demonstrated that this all-oral regimen is both effective and well-tolerated, even in patients with refractory disease.

With a very good partial response rate of 33% and a progression-free of 13 months, this triplet offers an alternative for patients prone to hospitalizations, falls, and other physical disabilities who may not tolerate more aggressive therapies.

As this combination progresses through further trials, it could represent a crucial step forward in the management of multiple myeloma in transplant-ineligible patients over the age of 65, providing them with a more convenient, effective, and safer treatment option.

Continue Learning about Treatment Advances for Older Myeloma Patients

Dr. Mateos, a myeloma expert from Spain, shares recent advancements that might allow older myeloma patients to access even more effective therapy- a treatment combining four medications. For more information, watch the video below.

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