The ASH annual meeting is the highlight of the year for myeloma specialists, shining a spotlight on the groundbreaking advances and innovations in diagnosing and treating myeloma, AL amyloidosis, and related conditions.

Myeloma UK will share their contributions as Dr Sandra Quinn, Myeloma UK, and Dr Martin Kaiser, Principal Investigator of Myeloma UK-funded OPTIMUM / MUK nine trial, present fantastic papers which will be highlighted elsewhere as Myeloma UK’s ASH coverage continues.

As the anticipation for ASH 2023 builds, Professor Graham Jackson, consultant haematologist and Myeloma UK’s Chief Clinical and Scientific Advisor, sheds light on the other top abstracts to watch, offering a curated glimpse into the forefront of myeloma research. Here, in no particular order, are his ‘Top 5’:

1. Iberdomide maintenance boosts post-ASCT response in newly diagnosed myeloma patients (Abstract 208)

In this phase II study, iberdomide, a CELMoD derived from the immunomodulatory agents lenalidomide (Revlimid®) and pomalidomide (Imnovid®), shows promise in enhancing post-autologous stem cell transplant (ASCT) responses. Early data indicate that 45–48% of patients treated with iberdomide maintenance experience an improved post-autologous stem cell transplant (ASCT) response. However, adverse effects such as haematological toxicity, fatigue, and infections are observed. The study, building on the efficacy of lenalidomide maintenance, presents an effective post-ASCT treatment, advancing remission-prolonging therapeutic strategy.

2. Newly diagnosed transplant-eligible myeloma patients with high-risk cytogenetics benefit from intensive treatment (Abstract 207)

A new treatment for newly diagnosed transplant-eligible patients with genetically high-risk disease is explored in this phase II trial. Consisting of six cycles of daratumumab (Darzalex®) in addition to KRD (carfilzomib (Kyprolis®), lenalidomide and dexamethasone) triplet combination (Dara-KRD), ASCT, Dara-KRD consolidation, second ASCT followed by two years of dara-lenalidomide maintenance, outcomes include progression-free survival (PFS) of 87% and an overall survival (OS) of 94% at two years. This reinforces the benefits of continuous therapy for patients with genetically high-risk myeloma and the importance of considering individuals’ cytogenetic profiles when determining optimal treatment.

3. Response and survival outcomes amplified by simple addition of cyclophosphamide to pomalidomide and dexamethasone treatment (PCD) (Abstract 1009)

Many novel innovations in myeloma are very expensive and not readily available. This phase III trial looks at the benefits of adding oral cyclophosphamide to pomalidomide and dexamethasone combination treatment (PCD) in heavily pre-treated myeloma patients. This simple and cheap addition to existing treatment increases overall response from 32% to over 55% and PFS from 5.8 to 10.9 months. Although some increase in haematological toxicity was experienced, in general the PCD triplet was well tolerated and provides a cost-effective and accessible option for this patient group.

4. Understanding the burden of infections experienced by patients with myeloma treated with bispecific antibodies (Abstract 1005)

Investigating infection burden in patients treated with anti-BCMA and anti-GPRC5D bispecific antibodies, this study observed 234 infections in 142 patients over a median follow-up of seven months. More than half of infectious events were grade 3 or above, and infections were responsible for an 8% mortality rate. Hospitalisation was required in 57% of cases, 13% resulting in ITU admission. Bacterial and viral infections were most common, despite prophylaxis. The study highlights that infections remain the critical long-term concern of these effective, novel anti-myeloma agents.

5. Daratumumab monotherapy could offer relatively non-toxic treatment option for newly diagnosed AL amyloidosis patients (Abstract 539)

This study examines the treatment of 40 AL amyloidosis patients (median age 70 years) with extensive cardiac involvement; a group typically very difficult to treat. Daratumumab monotherapy was investigated, allowing addition of bortezomib (Velcade®) and dexamethasone after cycle four if a very good partial response (VGPR) was not achieved (required by 25% of patients). At six months, over 77% had achieved a partial response (PR) or better; 37% in VGPR and 12% achieving complete response (CR). A cardiac response was observed in 27% of patients (6 months). OS was good at 73% (3 months) and 65% (6 months). Clearly, earlier diagnosis of cardiac amyloid is vitally important, but to date, this is one of the largest and most critical studies in the progression of viable treatment opportunities in this patient group.

This selective list is far from exhaustive. Amongst the packed programme, look out for other abstracts revealing breakthroughs on novel tri-specific agents, assessment of the immune status of teclistamab (Tecvayli®) responders and non-responders as well as trials exploring adaptations to induction and consolidation phases of ASCT.

The line-up demonstrates just how much world-class work is being put into tackling the problems of myeloma and related conditions and I’m looking forward to keeping abreast of all the latest findings.

Abstract references

Cellerin E, Jourdes A, Brousse X, et al. (2023). Cumulative Incidence and Characteristics of Infections Requiring Treatment, Delay in Treatment Administration or Hospitalisation in Patients with Relapsed or Refractory Multiple Myeloma Treated with Anti BCMA or Anti GPRC5D Bispecific Antibodies. Online Abstract: Accessed November 2023.

van de Donk N, Touzeau C, Terpos E, Perrot A, et al. (2023). Iberdomide Maintenance after Autologous Stem-Cell Transplantation in Newly Diagnosed MM: First Results of the Phase 2 EMN26 Study. Online Abstract: Accessed November 2023.

Kastritis E, Minnema M, Dimopoulos M, et al. (2023). Efficacy and Safety of Daratumumab Monotherapy in Newly Diagnosed Patients with Stage 3B Light-Chain Amyloidosis: A Phase 2 Study By the European Myeloma Network.
Online Abstract: Accessed November 2023.

Song Y, Kim J, Chim C, et al. (2023). Randomized Phase 3 Study of Pomalidomide Cyclophosphamide Dexamethasone (PCD) Versus Pomalidomide Dexamethasone (PD) in Relapse or Refractory Myeloma: An Asian Myeloma Network (AMN) Study. Online Abstract: Accessed November 2023.

Touzeau C, Perrot A, Hulin C, et al. (2023). Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone Induction and Consolidation with Tandem Transplant in High-Risk Newly Diagnosed Myeloma Patients: Final Results of the Phase 2 Study IFM 2018-04. Online Abstract: Accessed November 2023.