IMS 2024 Myeloma Oral Sessions Day 4

The final day of presentations at the International Myeloma Society (IMS) meeting in Brazil provided updates on the use of various treatments for patients with relapsed and refractory multiple myeloma. Let us break down the key findings for you…

Antibody Drug Conjugate Therapy

Blenrep (belanatamab mafodotin)

Results of a large trial of Blenrep (belanatamab mafodotin), a treatment called an antibody-drug conjugate, included 302 patients who had tried at least one prior line of therapy, showed Blenrep in combination with Pomalyst and dexamethasone (B-Pd) lowered the risk of disease progression or death by 48% compared to Velcade (bortezomib), Pomalyst, and dexamethasone (VPd) (Dimopoulos M, NEJM 2024). Results from from this study were presented in two abstracts on Saturday:

• Researchers reported a positive trend favored B-Pd for overall survival (OS) – the length of time a patient survives. Longer follow-up is needed as OS had not been reached after almost 22 months of follow-up (Abstract OA-62). Eye toxicity such as blurred vision and dry eye were the most common side effects with B-Pd treatment. Patients who experienced these side effects were given a lower dose of Blenrep and the side effects tended to resolve quickly, while patients continued to respond to treatment.
• In another abstract (Abstract OA-13), no difference in health-related quality of life – information on the physical and mental health status of individuals, and on the impact of disease and treatment on a patient’s quality of life – was observed in patients who received either B-Pd or VPd. These findings further support the use of Blenrep as a treatment option for patients once available.
• Additionally, an early phase trial of 18 patients with RRMM who received one prior line of therapy showed that the addition of Blenrep when combined with Kyprolis, Revlimid, and dexamethasone (B-KRd) led to impressive response rates and the commonly seen eye-related side effects, such as blurred vision, were low-grade and reported to be manageable (Abstract OA-57). In this study, Blenrep was given once every 8 weeks instead of every 4 weeks, and more than half the patients enrolled had high-risk cytogenetics. Additional results will be presented at future meetings.

Maintenance Therapy

Revlimid (lenalidomide)

Maintenance therapy with Revlimid (lenalidomide) is the standard of care following induction therapy and stem cell transplantation; however, Revlimid maintenance therapy can have side effects when given over a long period of time. In this study of 43 patients (Abstract OA-15), researchers evaluated if maintenance therapy can be stopped if patients are in minimal residual disease (MRD)-negative remission – that means doctors are not detecting cancer cells in the bone marrow or blood and patients don’t have any signs or symptoms of myeloma – after 3 years of Revlimid maintenance therapy. Researchers reported that 84% of patients maintained MRD-negative remission after 1 year of stopping Revlimid maintenance therapy. Ongoing studies are underway to better guide the decision to stop maintenance therapy in patients with MRD-negative remission.

Small Molecules for RRMM

Mezigdomide, tazemetostat, and dexamethasone

CELMoDs are a new class of myeloma drugs that work like immunomodulators such as Revlimid and Pomalyst and are orally administered. They also stimulate the immune system and kill myeloma cells directly, even for patients whose myeloma has become resistant to certain treatment. This abstract (Abstract OA-29) evaluated the combination of mezigdomide, an oral CELMoD, tazemetostat, a small molecule that blocks a protein called EZH2 to kill myeloma cells, and dexamethasone in RRMM. Researchers hope that when mezigdomide and tazemetostat work together, they attack the cancer from different angles, making the treatment more powerful. Results from an early phase trial that included 13 patients treated with mezigdomide, tazemetostat, and dexamethasone responded to therapy. Additional results will be presented at future meetings.

Sonrotoclax and dexamethasone

Finally, results from a small trial of a new treatment for relapsed/refractory patients who have a chromosomal rearrangement called t(11;14) – sonrotoclax, similar to venetoclax, showed more than 75% of patients responded to the treatment in combination with dexamethasone. More than 20% had a complete response with two patients achieving MRD negativity, meaning no myeloma was detected even with the most sensitive tools. The most common side effects were fatigue and insomnia (28% of patients each) followed by gastrointestinal side effects (less than 20% of patients). Side effects were low-grade in more than 90% of patients, suggesting this may be a promising option for patients with this disease characteristic.

Please be sure to tune into our 2-hour webinar on Wednesday, October 9^th from 10:00 AM–12:00 PM (ET) as myeloma experts recap each day’s clinical research and discuss what these findings mean for myeloma patients.

We look forward to more clinical updates in the months ahead!