The third day of presentations at the International Myeloma Society (IMS) meeting in Brazil offered a glimpse into the potential of new treatment strategies for patients with relapsed/refractory multiple myeloma (RRMM) and provided additional updates on quadruplet regiments for newly diagnosed multiple myeloma (NDMM).
Talvey (talquetamab), a GPRC5D-directed bispecific antibody, showed high response rates when used in different combinations, according to data from a pair of abstracts involving patients with RRMM who had received 1 or more prior lines of therapy.
An early phase trial (Abstract OA–01) that evaluated 77 patients who Talvey, Darzalex (daratumumab), Pomalyst (pomalidomide) led to high response rates. The most common side effects included loss of taste and dry mouth, as well as low white blood cell counts, and cytokine release syndrome (CRS), which presents as flu-like symptoms. This trial was notable for the fact that most patients had received an anti-CD38 antibody (94%) (Darzalex or Sarclisa) and Pomalyst (83%) prior to receiving this new triplet regimen. The findings suggest that combination Talvey, Darzalex and Pomalyst may be a potential treatment option even for those patients who had received Darzalex and/or Pomalyst and whose disease had eventually progressed.
In the next abstract (Abstract OA–03), researchers reported that Talvey combined with Tecvayli (teclistamab), a bispecific B-cell maturation antigen (BCMA)-targeted antibody, was safe and associated with high response rates in 94 patients with RRMM who received 3 or more prior lines of therapy. Infections, CRS, low white blood cell counts, and taste changes were the most common adverse effects; they were consistent with the side effects of each treatment and were manageable. Most notably, the combination treatment was very effective in treating extramedullary disease (EMD) which occurs when there are myeloma cells growing outside of the bone marrow. EMD has traditionally been difficult to treat with available therapies. Over 80 percent of patients still responded after 18 months, including patients with EMD. The combination is being studied in a larger trial to validate the results.
Researchers from Spain shared updates from CARTITUDE-4, the first randomized phase 3 study evaluating the efficacy and safety of Carvykti in 419 patients with RRMM that no longer responded to treatment with Revlimid (Abstract OA-65). Findings showed that treatment with Carvykti when compared to the standard of care (either Darzalex or Velcade combined with Pomalyst and dexamethasone) reduced the risk of death by 45%. These data continue to support the overall benefit-risk profile of Carvykti in patients with RRMM as early as after first relapse.
CAR T-cell therapy can be hampered by long production times that lead to significant delays in treatment. Thus, shortening CAR T-cell manufacturing time will enable patients with aggressive disease to receive treatment sooner. Several abstracts offered updates on recent advances in CAR T-cell therapy for RRMM.
Results from two new BCMA-directed (the same target as Abecma and Carvykti were presented:
P-BCMA- ALLO1, an off-the-shelf (meaning there is no waiting for the T-cells to be engineered and reinfused), BCMA-directed CAR T-cell therapy for RRMM was shown to have manageable side effects predominantly low white blood cell counts; CRS and neurologic side effects were lower grade than have been observed with the available CAR T-cell products in an early phase trial of 34 patients (Abstract OA-04). At the highest dose, 91% of patients responded. Ongoing studies will compare the response rates of this potential off-the-shelf CAR T-cell therapy for RRMM.
CAR T-cell therapies with mechanisms of action are also needed for patients who relapse following BCMA-directed therapy. An early phase clinical trial of 31 patients treated with BMS-986393, a GPRC5D CAR T-cell therapy, led to impressive response rates (96%) and side effects typical of GPRC5D-directed therapy (Abstract OA–08). Longer follow-up is needed as the median progression-free survival (PFS) – the time before the disease returned – had not been reached after almost 14 months of follow-up.
HDP-101, a new BCMA-directed antibody-drug conjugate (ADC) that has a different mechanism of action than Blenrep. Researchers reported that HDP-101 demonstrated encouraging safety and effectiveness in a small, early phase clinical trial of 18 patients with RRMM (Abstract OA–60). Future trials will evaluate the potential of this novel ADC for RRMM.
In the final abstract (Abstract OA-45), Dr Ashraf Badros from the University of Maryland and colleagues reported that minimal residual disease (MRD)-negativity rate more than doubled by 12 months when Darazlex was combined with Revlimid (D-R) in maintenance therapy compared to Revlimid alone, resulting in improvement in 30-month progression-free survival in patients with newly diagnosed multiple myeloma (NDMM) following stem cell transplant. 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 IMS 2024.
