Welcome to our final recap of the latest research on myeloma treatments presented at the American Society of Hematology (ASH) Annual Meeting in San Diego. Highlights from the final day included:
Let’s jump into the latest findings!
Researchers from Greece demonstrated that treatment with Darzalex can significantly delay the progression from smoldering multiple myeloma (SMM) to active disease in high-risk patients. Data from this abstract, simultaneously published in the New England Journal of Medicine (Dimopoulos et al.), showed that patients receiving Darzalex had a 51% lower risk of progression (that is the time until myeloma is detected) compared to those under active monitoring, the current standard of care after a median of more than 5 years of follow-up. The most common serious side effect in both arms was hypertension, affecting approximately 5%. Approximately 5% of patients in the Darzalex arm discontinued treatment.
High-risk SMM is an asymptomatic precursor to multiple myeloma, and early treatment strategies may improve outcomes for patients with a high risk of progression to active disease. The researchers emphasized that findings from this phase 3 trial specifically apply to patients with high-risk SMM. Future research will explore whether Darzalex alone or in combination with other medications could help prevent disease progression in patients with high-risk SMM.
Two abstracts showed that Sarclisa in combination with the current standard of care demonstrated significant treatment benefits in patients with newly diagnosed multiple myeloma (NDMM). Sarclisa is an anti-CD38 antibody in the same class as Darzalex and is administered intravenously.
The first abstract showed that Sarclisa in combination with Revlimid (lenalidomide), Velcade (bortezomib), and dexamethasone (Isa-VRd) induction therapy resulted in a 30% reduction in the risk of disease progression in transplant-eligible NDMM patients compared to VRd. Half of patients treated with Isa-VRd achieved minimal residual disease (MRD) negativity, indicating no detectable cancer cells, after 18 weeks of treatment. Side effects such as infections, diarrhea, and peripheral neuropathy were consistent with previous clinical trial findings of Isa-VRd.
In the next abstract, Dr. Orlowski and colleagues from MD Anderson Cancer Center reported that Isa-VRd induction therapy followed by maintenance with Isa-Rd demonstrated higher and sustained MRD negativity rates compared with the current standard of care in NDMM patients not eligible for a transplant. This analysis of the phase 3 study included 446 patients. Side effects of Sarclisa observed in this study were consistent with prior studies of Sarclisa and VRd.
Researchers conclude that Sarclisa-based quadruplets may represent an alternative new standard of care for patients with NDMM.
For patients with relapsed or refractory multiple myeloma considering treatment with Abecma (idecabtagene vicleucel), a CAR T-cell therapy, understanding factors that influence the effectiveness and side effects is important. Currently it is available for patients who have had two or more prior lines of therapy.
In a study of 108 patients, Dr. Hansen and researchers from the H. Lee Moffitt Cancer Center found that patients with high disease burden, such as advanced disease stage, and the presence of biomarkers of inflammation like ferritin and C-reactive protein before starting Abecma treatment were more likely to develop side effects such as neurotoxicity (ICANS). Patients who had extramedullary disease (ie, the presence of myeloma cells outside of the bone marrow) and those who had received prior treatment with a BCMA-targeting agent were less likely to have durable responses.
These findings highlight the importance of pre-treatment factors in shaping outcomes with ide-cel therapy and may help guide personalized approaches to optimize benefits while managing risks.
In the next abstract, researchers in the United Kingdom reported that treatment with Carvykti led to significantly higher rates of MRD-negativity in patients with RRMM who have received at least one prior line of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), compared to standard therapies of Pomalyst (pomalidomide), Velcade, and dexamethasone (PVd) or Darzalex, Pomalyst, and dexamethasone (DPd). Carvykti is currently available for patients who have had one or more prior lines of therapy. These findings further support the use of Carvykti patients with Revlimid-refractory MM.
Dr. Dima and researchers at the Cleveland Clinic Taussig Cancer Institute looked at how effective Tecvayli, a BCMA-targeting bispecific antibody, is for patients with relapsed/refractory multiple myeloma (RRMM) who previously received other BCMA-directed therapies like CAR T-cell therapy or antibody-drug conjugates (ADC). In this abstract, researchers found that while Tecvayli is effective for these patients, outcomes were generally better for those who hadn’t received prior BCMA treatments. Currently, it is available for patients who have had four or more lines of therapy.
Patients previously treated with BCMA-directed therapy had slightly lower response rates to and shorter median progression-free survival (PFS, time before the disease worsened) compared to for those without prior BCMA-directed therapies. The study also highlighted the importance of timing between BCMA-directed therapies. Patients who waited more than 9 months after their last BCMA-directed therapy before starting Tecvayli had better outcomes. Side effects like CRS and neurotoxicity (ICANS) were similar regardless of prior BCMA therapy; however, patients with prior BCMA-directed therapy were more likely to experience low platelet counts early in treatment. These findings suggest that Tecvayli is a valuable option for patients previously treated with BCMA therapies, and patients and caregivers should discuss the timing of starting Tecvayli with their healthcare team.
Dr. Tomasson and colleagues from the University of Iowa reported that Elrexfio, a bispecific antibody targeting BCMA, in combination with Kyprolis (carfilzomib) and dexamethasone shows promise for treating patients with RRMM. Currently, Elrexfio is available for patients who have had four or more lines of therapy.
In this abstract, researchers data from an early-phase study involving 12 patients, all of whom had received at least one or more prior lines of therapy. The most common side effects included fatigue, mild cytokine release syndrome (CRS), and low blood counts. Further studies ongoing will evaluate the benefits of Elrexfio combined with Kryprolis and dexamethasone in a larger population.
Researchers from Brazil reported that belantamab mafodotin combined with Velcade and dexamethasone (BVd) shows significant overall survival benefit, reducing the risk of death by 42% in multiple myeloma at or after first relapse compared to Darzalex with Velcade and dexamethasone (DVd). In this abstract, data was analyzed from 494 patients, of which 51% of patients had received 1 previous line of therapy, 52% had received prior Revlimid, while 34% of patients no longer responded to Revlimid; 28% had high-risk chromosomal abnormalities. The researchers note that additional studies will shed light on if BVd may be a potential new standard of care in MM at first relapse or later.
Cevostamab is an investigational bispecific antibody that targets FcRH5, a new target on myeloma cells. In this study of 167 heavily pretreated patients (between 2 and 18, with a median of 6), Dr. Richter and researchers at Mount Sinai found that cevostamab demonstrated good response rates. Patients who had not previously received BCMA-targeted therapies responded better than those who had. Almost all patients (96%) were resistant to all three standard treatment classes: proteasome inhibitors, immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies. A majority (57%) of patients had received one or more prior BCMA-targeted therapy. Common side effects included CRS, low white blood cell counts, and fatigue. Further analysis will evaluate the use of cevostamab in larger trials.
CELMoDs are a new class of oral myeloma drugs that work like immunomodulators such as Revlimid and Pomalyst. They also stimulate the immune system and kill myeloma cells directly, even for myeloma that has become resistant to certain treatment. Researchers from Canada presented their findings from an early phase trial evaluating mezigdomide, an oral CELMoD, in combination with dexamethasone and either Velcade (Mezi-Vd) or Kyprolis (Mezi-Kd). In this study, 77 patients who have had one or more prior lines of therapy received Mezi-Vd and 27 patients received Mezi-Kd. The authors reported that Mezi-Vd and Mezi-Kd demonstrated high response rates and side effects such as low white blood cell counts, infections, and low platelet counts.
Researchers from Israel reported data from an early phase clinical study of HBI0101, an anti-BCMA CAR T-cell therapy. Their study included 84 patients, most of whom were triple class refractory, showed high response rates and MRD negativity rates in patients treated with HBI0101. Common side effects included CRS, low white blood cell, low red blood cell, and low platelet counts.
Dr. Freeman and researchers at the H. Lee Moffitt Cancer Center reported their findings from an early phase trial evaluating anitocabtagene autoleucel, another anti-BCMA CAR T-cell therapy. The trial included 58 patients with RRMM who have received at least three prior lines of treatment. Patients treated with anitocabtagene autoleucel achieved high response rates and MRD negativity rates. Common side effects observed were CRS, low white blood cell, low red blood cell, and low platelet counts.
Further analysis will evaluate the use of these new therapies in larger trials.
We hope you enjoyed our daily recap of the latest advances in myeloma treatment. Keep an eye on themmrf.org for future updates!
