More than 40,000 people attended the American Society of Clinical Oncology (ASCO) Annual Meeting (ASCO 2019) which was held in Chicago from 31 May until 4 June. This meeting brings together oncology and haematology professionals from across the globe to discuss the latest scientific and treatment developments in the field.
A number of myeloma topics were presented in this important scientific meeting. The most important updates are outlined below.
Smoldering myeloma
- A new risk stratification model was presented at ASCO 2019 to identify smoldering multiple myeloma (SMM) patients with high risk to progress to myeloma. 2004 patients were included if they had no disease progression within 6 months, had baseline data from diagnosis (+/- 3 months), had a follow up of ≥1 year, and did not participate in a therapeutic trial of SMM. Various clinical and laboratory factors were explored to identify factors that predicted progression at 2 years. The researchers developed a risk stratification model for SMM that incorporates revised cut-offs for previously used parameters that can be universally applied. Additional analysis is being conducted to develop models that utilise common cytogenetic abnormalities, as well as those without free light chain tests given lack of availability of all tests across the world.
Read the full abstract here.
- In the last few years, a lot of clinical trials have suggested the benefit of treating smoldering myeloma patients to prevent the progression to myeloma. Dr Sagar Lonial, MD, Chief Medical Officer at Winship Cancer Institute of Emory University, Atlanta, US, presented a phase II/III E3A06 randomised clinical trial to show that lenalidomide significantly reduces the risk of smoldering multiple myeloma (SMM) from progressing to cancer in patients at moderate or high risk. This treatment could become a standard of care for high-risk smoldering myeloma patients.
Read more information about this research here.
Transplant-eligible newly diagnosed myeloma patients
- The Phase 3 randomised study CASSIOPEIA compares the standard of care VTD (bortezomib, thalidomide and dexamethasone) with this standard plus daratumumab (D-VTD) as an induction prior to and consolidation treatment after autologous stem-cell transplantation (ASCT). According to the results adding daratumumab to VTD improved depth of response – stringent complete response (sCR) ≥ complete response (CR) and minimal residual disease (MRD) negativity – and progression free survival (PFS) with acceptable safety. The favourable benefit-risk profile supports the use of D-VTd in this group of patients. CASSIOPEIA is the first study to demonstrate the clinical benefit of dartumumab + the standard of care in transplant-eligible newly diagnosed myeloma patients.
Read the full abstract here.
- Autologous stem-cell transplantation (ASCT) is a standard of care for transplant-eligible newly diagnosed myeloma patients. However, this procedure has side effects and might be a difficult process for patients. According to a clinical trial presented at ASCO 2019, high and comparable rates of minimal residual disease (MRD) negativity were seen with the combination of carfilzomib, lenalidomide and dexamethasone (KRd) with or without transplantation in newly diagnosed myeloma. That would mean to avoid ASCT at least in a group of patients. According to results from the FORTE trial, KRd-ASCT-KRd and 12 KRd cycles (KRd12) were equally effective in inducing high-quality responses, with about 50% of high-risk patients achieving MRD negativity.
Read the full abstract here.
Relapsed or Refractory Myeloma (RRMM)
- A non-inferiority phase 3 study compared efficacy and safety of subcutaneous (SC) versus intravenous (IV) daratumumab. 522 patients were randomized (n=263 SC; n=259 IV) with median age of 67 years old. Efficacy and pharmacokinetics (PK), co-primary endpoints, were met demonstrating non-inferiority of daratumumab SC to IV. Additionally, daratumumab SC significantly decreased infusion-related reactions (IRR) rate and administration time, with a comparable safety profile to DARA IV. This route of administration is significantly better from the patient perspective as the duration of injection was 5 minutes for daratumumab SC compared with 421/255/205 minutes for the first/second/subsequent daratumumab IV infusions.
Read the full abstract here.
- Pomalidomide and low-dose dexamethasone is the standard of care for relapsed or refractory myeloma patients who received two or more prior lines, including lenalidomide and a proteasome inhibitor (PI). Pivotal Phase 3 ICARIA-MM trial shows that isatuximab in combination with pomalidomide and dexamethasone resulted in an impressive 40% reduction in the risk of progression or death compared to pomalidomide and dexamethasone alone. According to the results, this new combination significantly improved progression free survival (PFS) and overall response rate (ORR) vs Pd, with a manageable safety profile. IsaPd is an important new treatment option for the management of RRMM.
Read more information about this research here.
New drugs
- Iberdomide is a novel cereblon E3 ligase modulator (CELMoD) with enhanced tumoricidal and immunostimulatory activities. Preclinically, this drug overcomes immunomodulatory drug (IMiD) resistance and has synergy with daratumumab, bortezomib and dexamethasone. First clinical (phase 1b/2a) study was presented at ASCO 2019 to evaluate the maximum tolerated dose (MTD), safety, and preliminary efficacy of iberdomide. According to the results presented, iberdomide plus dexamethasone showed favourable efficacy and safety in heavily pre-treated patients with RRMM who did not respondto prior therapies. This study is ongoing, including combinations of iberdomide with daratumumab or bortezomib.
Read the full abstract here.
- Data about another new drug was presented in this important scientific congress. The updated results of a first-in-human (FIH) phase I dose escalation study which evaluate AMG 420, an anti-BCMA bispecific T-cell engager (BiTE) immunotherapy, in relapsed or refractory myeloma (RRMM). In this FIH study of AMG 420 there was a 70% response rate (7/10) with 5 out of 7 responders achieving a stringent complete response (sCR) at 400 µg/d, a recommended dose for further investigation.
Read more information about this research here.
