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MMRF ASH 2024 Blog: Day 2

Welcome to the second day of our recap of the latest findings on myeloma treatments reported at the American Society of Hematology (ASH) meeting in San Diego.

Highlights from today included:

Let’s take a closer look!

Tecvayli (Teclistamab)

Newly diagnosed multiple myeloma

Several abstracts highlighted promising results on the use of Tecvayli (teclistamab) in combination with other drugs for patients with newly diagnosed multiple myeloma (NDMM) and those who relapse after one or more line of treatment. Currently, it is available for patients who have had four or more lines of therapy.

In the first abstract, 49 patients with transplant-eligible NDMM were treated with Tecvayli in combination with Darzalex, Revlimid, and dexamethasone with or without Velcade (Tec-DRd) or (Tec-DVRd) as induction therapy. Researchers from Germany reported that 35 of 36 patients who completed at least 3 treatment cycles achieved minimal residual disease (MRD) negativity, indicating no detectable cancer cells. The most common side effects were infections and cytokine release syndrome (CRS), which presents as flu-like symptoms and is a common side effect of the bispecific antibodies. Further analysis will evaluate these combinations in larger trials.

Maintenance therapy

Revlimid maintenance therapy after autologous stem cell transplantation (ASCT) has been the standard-of-care for transplant-eligible NDMM. However, patients eventually relapse, supporting the need for better strategies for maintenance therapy. In this abstract, researchers from Italy reported data from an early phase trial that Tecvayli with or without Revlimid could be safely given as maintenance therapy for 90 patients with transplant-eligible NDMM. Common side effects included infections, low white blood cell counts, CRS, cough, diarrhea, and fatigue. All patients enrolled in the study who received Tecvayli with or without Revlimid as maintenance therapy achieved MRD negativity. These findings support the ongoing study of Tecvayli alone or in combination with Revlimid as maintenance therapy.

Relapsed/refractory multiple myeloma

In the next abstract, Dr. D’Souza and colleagues at the Medical College of Wisconsin showed that Tecvayli in combination with Darzalex and Pomalyst may lead to better responses, especially in patients with relapsed or refractory multiple myeloma (RRMM) who had one or more lines of therapy. Common side effects reported in this early phase trial of 27 patients with RRMM were infections, low white blood cell, red blood cell, and low platelet counts. The researchers concluded that, pending the results of a larger study, Tecvayli in combination with Darzalex and Pomalyst may be a new triplet therapy for early relapsed myeloma.

New Bispecific Antibody

Etentamig (formerly ABBV-383) is a new bispecific antibody that targets B-cell maturation antigen (BCMA) that is being evaluated with monthly dosing from the beginning of treatment, unlike Tecvali and Elrexfio which are administered weekly through 24 weeks after initial step-up.

Dr. Rodriguez and colleagues at Mount Sinai presented results from an early phase trial of ABBV-383 combined with Darzalx and dexamethasone in this abstract. The study, which aimed to identify the best dosage of ABBV-383, included 60 patients who received 3 or more prior lines of therapy including a proteasome inhibitor and an immunomodulatory drug. Of this group 70% had received anti-CD38 mAb therapy. Most common side effects included low platelet, white blood cell, and red blood cell counts, CRS and fatigue. Their findings suggest that ABBV-383 in combination with Darzalx and dexamethasone is tolerable and early response rates were promising. Ongoing trials will offer more information on the potential use of ABBV-383 in RRMM.

Antibody Drug Conjugate Belantamab Mafodotin

In this abstract, Dr. Usmani and colleagues from Memorial Sloan Kettering Cancer Center showed belantamab mafodotin combined with VRd led to good response rates in patients with NDMM who are ineligible for transplant. Vision problems were the most common side effect. These side effects were managed by briefly stopping treatment or reducing the dose of belantamab mafodotin, allowing most patients to continue treatment. With these promising results, future studies will continue to evaluate the potential of belantamab mafodotin in patients with newly diagnosed disease.

Maintenance Therapy

In the final abstract, Dr. Foster colleagues at the University of Virginia reported that Darzalex in combination with Revlimid maintenance therapy resulted in better remission rates (MRD-negative) and longer disease control compared to Revlimid alone. The researchers evaluated data from the phase 3 AURIGA study that included 200 transplant-eligible NDMM patients who were MRD-positive after ASCT regardless of age, race, or risk profile. Findings from this trial revealed that maintenance therapy with Darzalex combined with Revlimid prolonged the time to disease progression across all subgroups of patients, including those with high-risk disease. Low white blood cell counts and infections were the most common side effects observed in this phase 3 trial of 200 patients with NDMM.

The researchers conclude that these results further support adding Darzalex to Revlimid maintenance therapy for patients with NDMM following stem cell transplant.

Be sure to come back tomorrow for our final day of updates in the treatment of myeloma at ASH 2024.