Welcome to our recap of the latest findings on myeloma treatments reported at the European Hematology Association meeting that kicked off Thursday in Madrid, Spain. Clinicians and researchers gathered to present and discuss several updates in multiple myeloma relating to:
Let us break down the key findings for you…
On Thursday, a late-breaking abstract (Abstract: LBA3440) presented by researchers from Greece showed Blenrep in combination with Pomalyst (pomalidomide) and dexamethasone (Pd) lowered the risk of disease progression or death by 48% compared to Velcade (bortezomib) plus Pd. Results of the phase 3 DREAMM-8 trial, which included 302 patients who have tried at least one prior line of therapy, including Revlimid (lenalidomide), were presented a couple of weeks ago at the American Society of Clinical Oncology (ASCO) annual meeting and also published in the New England Journal of Medicine (Dimopoulos M, NEJM 2024).
Side effects of the combination of Blenrep with Pd (BPd) were consistent with previous clinical trials of Blenrep.
In a second abstract (Abstract: S214) on Blenrep , researchers from Spain presented data from the phase 3 DREAMM-7 study that showed Blenrep in combination with Velcade (bortezomib) and dexamethasone (BVd) more than doubled progression-free survival (PFS), that is the time until disease progression, compared to Darzalex (daratumumab) in combination with Vd (36 vs 13 months). Results of the trial, which included 494 patients who had received 1 or more prior lines of therapy but no prior treatment with an anti-BCMA therapy, were presented earlier at ASCO and published in the New England Journal of Medicine (Hungria V, NEJM 2024).
Side effects of the BVd were consistent with previous clinical trials of individual drugs. Most common side effects were low platelet counts, blurred vision, and dry eye. Eye problems were generally reversible and manageable with dose modifications. Despite the higher incidence of eye issues in patients who received BVd, overall patient-reported health-related quality of life did not differ substantially between the treatment groups over time.
Taken together, the results from the two clinical trials represent a second opportunity for Blenrep, which was taken off the US market in November of 2022 following the request of the U.S Food and Drug administration (FDA) as the phase 3 trial did not meet its primary endpoint. Blenrep was originally granted accelerated approval in August 2020, based on a single arm trial, by the FDA for relapsed/refractory patients who had received at least four prior treatments.
Results from these trials indicate that the original indication for Blenrep, which recommended administration once every three weeks at 2.5 milligrams per kilogram of body weight, had not been optimized for patients; these studies took a different approach, resulting in fewer side effects for patients. In DREAMM-8, the initial dose of Blenrep was the same, however subsequent doses were lowered to 1.9 milligrams per kilogram and administered every four weeks. Researchers noted that the dose reductions and the use of lubricating or moisturizing eye drops helped improve treatment outcomes in patients.
New data continue to confirm that a four-drug combination for newly diagnosed patients is a new standard of care. In the primary analysis of the phase 3 PERSEUS trial, researchers showed that subcutaneous Darzalex in combination with Revlimid, (lenalidomide), Velcade (bortezomib), and dexamethasone (D-VRd) followed by Darzalex plus Revlimid (D-R) maintenance reduced risk of progression or death by 58 percent compared to VRd in patients with newly diagnosed multiple myeloma (NDMM) who received a stem cell transplant.
Researchers from the Netherlands presented additional data from the PERSEUS trial. Their analysis (Abstract: S201) of minimal residual disease (MRD) negativity—that is no disease was detected after treatment—showed that MRD negativity rates were higher with D-VRd compared to VRd for after 3 years (65% vs 30%).
The authors conclude that these results support a D-VRd quadruplet induction and consolidation regimen and D-R maintenance regimen as the standard of care for NDMM patients deemed eligible for a stem cell transplant.
Data from 2 abstracts presented at EHA 2024 showed that adding Sarclisa (isatuximab), which is in the same class of treatments as Darzalex, to RVd improves outcomes in patients with NDMM.
The BENEFIT trial showed Sarclisa (isatuximab) in combination with VRd (Isa-VRd) significantly increased the MRD negativity to 47% compared to 24% in patients who were treated with IsaRd, according to data presented by researchers in France (Abstract S202). The phase 3 BENEFIT study included patients aged 65-79 years with NDMM who were determined to be ineligible for a stem cell transplant.
In the next abstract (Abstract S203), German researchers revealed their interim analysis of the GMMG-HD7 trial, which demonstrated that the addition of Sarclisa to VRd (Isa-VRd) and high-dose therapy (melphalan) followed by stem cell transplant improved MRD negativity rates compared to VRd alone (72% vs 57%).
Findings from both studies further support the use of Isa-VRd as a new standard of care for patients with NDMM.
The first abstract (Abstract: S205) highlighted findings from an analysis of the CARTITUDE-2 study that evaluated Carvykti with or without Revlimid maintenance in patients who achieved less than a CR after transplant ASCT and frontline therapy.
Researchers from the Netherlands noted that a single infusion of Carvykti with or without Revlimid maintenance demonstrated deep and durable responses. Of the 17 patients treated with Carvykti 94% achieved an ORR, with 94% also achieving a CR or better. The safety profile was like prior trials of Carvykti with or without Revlimid maintenance. After 22 months of follow up, the most common side effects were low white blood cell counts, cytokine release syndrome (CRS) or flu-like symptoms, neurotoxicity, and infections.
Further studies, with a median follow up greater than 2 years, will continue to examine the potential role of CAR T-cell therapy in frontline treatment of patients.
Patients with MM who relapse early after induction therapy and stem cell transplant have a poor prognosis. In the pivotal phase 2 KarMMa study, treatment with Abecma resulted in frequent, deep, and durable responses in patients who were had received all major classes of treatments and no longer responded to their last treatment. Ongoing studies are evaluating the potential use of CAR T-cell therapy in earlier lines of therapy.
In the next abstract (Abstract: S208), French researchers reported that 94% of NDMM transplant-eligible patients whose disease progressed less than 18 months after receiving first line therapy achieved a response following a single infusion of Abecma. Of the 31 patients who received Abecma, low white blood cell counts, low platelet counts, CRS, and infections were the most common side effects.
CAR T cell therapies targeting B‑cell maturation antigen (BCMA) have resulted in unprecedented responses in RRMM; however, relapses are frequent, and the development of new approaches is needed. Four abstracts presented at EHA 2024 highlighted results from early phase clinical trials on investigational CAR T-cell therapies for NDMM and RRMM.
GC012F is a new, dual-targeting CAR-T cell therapy that binds to BCMA and CD19 on myeloma cells and is manufactured within 24 hours of removal of plasma from a patient. Researchers from China colleagues reported their findings from an early phase trial that included 22 patients with high-risk NDMM who were eligible for a stem cell transplant-eligible (Abstract S200). Patients were considered high-risk if they had one or more of the following features: R-ISS-2 or-3; del17p, t(4;14), t(14;16), or 1q21amp; or extramedullary disease.
Following 23 months of follow up, the results showed all patients achieved a response and MRD negativity with GC012F. Low-grade CRS was the main side effect reported in this early phase study. The authors conclude that these promising preliminary results require further assessment of GC012F for NDMM with more patients and longer follow-up.
Chinese researchers reported their findings from an early phase clinical trial that evaluated a single infusion of equecabtagene autoleucel in high-risk NDMM patients who were deemed ineligible for a stem cell transplant. Findings from their abstract (Abstract S206) showed that all 16 patients who received equecabtagene autoleucel achieved a response and were MRD negative 7 months after treatment. High-risk features were defined as one or more of the following: R-ISS-3; del17p, t(4;14), t(14;16), or 1q21amp; or extramedullary disease. The most common side effects were infections, CRS, and low white blood cell counts.
Findings from an early phase trial showed that all patients achieved a response and 89% achieved MRD negativity after one-year of receiving a single dose of anitocabtagene autoleucel. The abstract (Abstract S207), presented by Dr. Matthew Frigault and colleagues from Massachusetts General Hospital Cancer Center, included data from 38 patients with RRMM who had received 3 or more lines of prior therapy. Anitocabtagene autoleucel has a unique protein, called a D-Domain, that is designed to bind more firmly to BCMA and reduce the risk of side effects such as CRS. Researchers reported that CRS and neurotoxicity as the most common side effects observed with anitocabtagene autoleucel therapy.
In this abstract (Abstract S209), researchers from China showed that 92% of patients with RRMM who received a single infusion of zevorcabtagene autoleucel achieved a response. The early phase study included 102 patients with RRMM who had received at least 3 prior lines of therapy. Researchers noted that CRS, neurotoxicity, and infections were the most common side effect observed.
Salvage therapies for patients who are refractory or relapse following BCMA-targeted therapy remains an urgent unmet need. Cevostamab, a bispecific antibody that targets the antigen FcRH5, has shown promising activity in heavily pretreated patients with RRMM in early phase clinical trials.
In this abstract (Abstract S210), Dr. Shaji Kumar and colleagues from the Mayo Clinic reported their findings from an early phase CAMMA 2 STUDY in 21 patients with RRMM whose disease no longer responds to the major classes of drugs and have received a prior BCMA-targeted agent, such as Blenrep or CAR T-cell therapy. The preliminary results showed that 67% of patients achieved a response with cevostamab.
Linvoseltamab is another investigational BCMA-targeting bispecific antibody for patients with RRMM who previously received 3 or more prior treatments. With 14 months follow-up, Dr Suzanne Lentzsch and colleagues from Columbia University showed an overall response rate of 71% for patients receiving linvoseltamab.
Additional results from this abstract (Abstract S212) revealed that 67% of patients with high-risk cytogenetics achieved a response. Infections, CRS, and low white and red blood cells counts were the most common side effects observed in patients receiving linvoseltamab. The phase 3 trial, LINKER-MM3, will be initiated in patients with RRMM and could provide some insight on the clinical role of linvoseltamab.
In the final abstract (Abstract S211) researchers from Germany reported that 60mg once weekly ABBV-383 monotherapy was the optimal therapeutic dose for patients with RRMM who received
3 or more prior lines of therapy, including All major classes of drugs. 65% of patients who received 60mg once weekly ABBV-383 monotherapy achieved a response. CRS, low white and red blood cells counts, as well as low platelet counts were the most common side effects observed in patients receiving ABBV-383.
The Phase 3 trial CERVINO was recently started and will evaluate the efficacy, safety, and tolerability of ABBV-383 monotherapy compared with standard available therapies in patients with RRMM who have received at least two lines of prior therapy.
Keep an eye out for MMRF updates from the 21st International Myeloma Society annual meeting in September!
