The 2023 American Society of Clinical Oncology (ASCO) annual meeting was held from June 2 to 6 in Chicago! Clinicians and researchers gathered to present and discuss several updates in multiple myeloma relating to:
Let us break down the key findings for you…
New data on both Carvykti and Abecma, which are FDA approved CAR T-cell therapies that target BCMA on myeloma cells, was reported.
Carvykti is approved for patients with multiple myeloma (MM) after at least four previous treatments. Given the success of CAR T-cell therapy in patients who have failed many different treatments and have relapsed/refractory MM (RRMM), there is an interest in testing CAR T-cell therapy for patients who have received fewer prior therapies.
In a late-breaking abstract presentation, Dr. Binod Dhakal and colleagues reported their findings 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 LBA106). Findings from CARTITUDE-4 were simultaneously published in the New England Journal of Medicine. The study compared Carvykti with standard of care treatments (Pomalyst, Velcade, and dexamethasone [PVd] or Darzalex, Pomalyst, and dexamethasone [DPd]) in Revlimid-refractory patients who received one to three prior lines of therapy, including a proteasome inhibitor and an IMiD. The results showed:
These findings demonstrate the dramatic benefit of Carvykti over the standard of care in 1 to 3 prior lines of therapy and highlight the potential for Carvykti to be a promising new treatment option for patients in this setting.
In a separate presentation, Dr. Yi Lin and colleagues from the Mayo Clinic reported final results from CARTITUDE-1, which was a phase 1/2 study of Carvykti in heavily pretreated patients with RRMM—in individuals who received 3 prior lines of therapy or were double refractory to a proteasome inhibitor (PI) such as Velcade, Kyprolis or NInlaro and immunomodulatory drug (IMiD) such as Revlimid or Pomalyst; and had received prior PI, IMiD, and anti-CD38 antibody therapy (ie, Darzalex or Sarclisa). (ABSTRACT 8009). A previous publication by Dr. Thomas Martin and researchers from the University of California, San Francisco reported an overall response rate (ORR) of 98%. These updated results, including analyses of high-risk patient subgroups, showed heavily pretreated patients with RRMM were able to live an average of 35 months before their myeloma progressed.
A longer median progression free survival (PFS)—that is, the length of time during and after treatment in which a patient is living with a disease that does not get worse—was observed after a single infusion of Carvykti than any previously reported therapy in heavily pretreated patients with RRMM. Patients continue to be followed for safety and survival in the CARTITUDE long-term study.
A pair of presentations highlighting recent findings on Abecma, the first CAR T-cell therapy approved for RRMM, were presented. Researchers presented patient-reported outcomes on health-related quality of life from the phase 3 KarMMa-3 trial (ABSTRACT 8032). Health-related quality of life captures 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. The results from the patient-reported outcomes showed statistically significant and clinically meaningful improvements in health-related quality of life including cognitive functioning, fatigue, and pain reduction for patients with RRMM who received Abecma compared with standard treatment regimens.
Adam Sperling and colleagues from Dana-Farber Cancer Institute reported updated results from a phase 1 study of BCMA-targeting CAR T PHE885 (ABSTRACT 8004), which uses a new development process that shortens the manufacturing time from several weeks to less than two days. The results showed an ORR of 100% in patients who received the highest dosage of PHE885 and 98% in all 49 patients. CRS was observed in 96% of patients, which is a similar rate seen in patients receiving CAR T-cell therapy. Only 28% of patients required bridging chemotherapy. A phase 2 study is underway in patients with RRMM, and evaluation in earlier lines of therapy is about to begin.
Tecvayli was the first approved off-the-shelf BCMA-directed bispecific antibody for the treatment of patients with RRMM. The approval was based on data from the pivotal phase 1/2 MajesTEC-1 study, which showed an ORR of 63% in patients who received Tecvayli. In this presentation, Dr Niels van de Donk and colleagues from the Netherlands presented updated findings. Patients had a median of 5 prior treatments (92% Darzalex exposed; 78% triple-class refractory; 81% Darzalex-refractory).The results showed:
These long-term follow-up data support Tecvayli as a safe and effective off-the-shelf BCMA bispecific therapy for patients with RRMM.
Dr. Yael Cohen and researchers from Israel reported initial results from the phase 1 RedirecTT-1 trial that examined the combination of Tecvayli with talquetamab, an investigational bispecific antibody targeting GPRC5D, an immunotherapeutic target like BCMA on myeloma cells (ABSTRACT 8002). This trial is the first to test the combination of two bispecific antibodies with two different myeloma cell targets (that is, BCMA and GPRC5D) with the hope of overcoming resistance to single agent bispecific antibody therapy. The goals of this study were to evaluate safety and identify an optimal dosage of the combination of bispecific antibodies. The results showed:
Combining BCMA-targeted Tecvayli with GPRC5D-targeted talquetamab yielded high response rates in patients with RRMM and support the continued evaluation of this combination therapy.
Dr. Bhagirathbhai Dholaria and colleagues from Vanderbilt University Medical Center reported findings from the phase 2 TRiMM-2 study in patients with heavily pretreated RRMM who received investigational talquetamab in combination with Darzalex (ABSTRACT 8003). The study included some patients who were previously exposed to anti-CD38 (88%) inhibitors like Darzalex or Sarclisa, BCMA-targeted therapy (54%), and CAR-T therapy (17%). Patients in the TRiMM-2 study were treated with talquetamab at a dose of either 0.8 mg/kg every two weeks or 0.4 mg/kg weekly in addition to Darzalex. The ORR was 84% for patients who received the higher dose of talquetamab and 71% for those who were treated with the lower dose. Ongoing studies will continue to examine the clinical potential of this combination of therapy.
Dr. Carolina Schinke from University of Arkansas for Medical Sciences presented updated findings from the phase 1/2 MonumenTAL-1 study of talquetamab in patients with RRMM (ABSTRACT 8036). Patients were treated with talquetamab at the recommended phase 2 dose (RP2D) of 0.8 mg/kg biweekly or 0.4 mg/kg weekly with step-up doses. The results showed:
Elranatamab is an investigational off-the-shelf BCMA-directed bispecific antibody in the same class as Tecvayli, being evaluated as monotherapy in patients with RRMM. In this presentation, Dr. Mohamad Mohty and colleagues from France reported findings from the MagnetisMM-3 study that showed 61% patients who have not been exposed to a prior BCMA-directed therapy achieved a response to elranatamab monotherapy (ABSTRACT 8039). The most common side effects were CRS (66%) and low red blood cell counts (59%).
In a separate presentation, Dr. Ajay Nooka and colleagues from Emory University reported their findings from a pooled analysis of patients treated with prior BCMA-directed therapies enrolled in the MagnetisMM program (ABSTRACT 8008). The results showed:
These results support elranatamab monotherapy as a treatment option for patients with RRMM who have been pre-treated with another BCMA-targeting agent.
Linvoseltamab is another investigational BCMA-targeting bispecific antibody for patients with RRMM who previously received 3 or more prior treatments. Dr Hans Lee and researchers presented findings from the phase 2 LINKER-MM1 trial that tested 50 mg and 200mg dosages of linvoseltamab (ABSTRACT 8006). The results showed an overall response rate of 71% for patients who received the 200 mg dose and 50% for those who were treated with 50 mg of linvoseltamab. Cytokine release syndrome was the most common side effect observed in patients receiving either dosage. A phase 3 trial, LINKER-MM3, will be initiated in patients with RRMM.
In patients with newly diagnosed multiple myeloma (NDMM), triplet or quadruplet induction regimens, high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) remain a standard of care. Empliciti is approved in combination with other medications such as Revlimid or Pomalyst and dexamethasone for patients with RRMM, but its role in NDMM has not been studied. In this clinical trial (ABSTRACT 8000), Dr. Stefan Krop and researchers from Germany compared Empliciti plus Kyprolis, Revlimid, and dexamethasone (KRd) to KRd in transplant-eligible NDMM patients up to 70 years. The results showed the addition of Empliciti to KRd significantly improved the rate of early, deep minimal residual disease (MRD)-negative remission (50% Empliciti-KRd vs 35% KRd) in transplant-eligible NDMM. Future studies will explore the potential role of Empliciti in NDMM.
While maintenance or continuous therapy with Revlimid is the current standard of care for patients with standard-risk myeloma following induction therapy and ASCT, current data suggest those with high-risk myeloma should receive a proteasome inhibitor such as Velcade, either as a single agent or combined with Revlimid, or even a triplet like Velcade, Revlimid, and dexamethasone (VRd).
Dr. Ajay Nooka and colleagues from Emory reported their findings of a phase 2 trial that assessed KPd as maintenance therapy patients with high-risk myeloma (ABSTRACT 8001). More than half of patients (59%) enrolled in the single arm trial were Black. High-risk myeloma was defined by the presence of certain changes in a patient’s DNA such as translocation of (4;14) or (14;16), deletion of 17p, gain of 1q, or greater than 20% circulating tumor cells. Double-hit myeloma (as defined by the presence of 2 or more high-risk genetic mutations was seen in 59% of patients in this study. The results showed:
In patients with high-risk myeloma, KPd maintenance deepened responses and may be able to fill an unmet treatment need in this patient population. Be sure to hear what myeloma experts have to say about the meeting’s presentations here.
