Preparing for the EHA25 — Highlights from 2019 and abstracts to watch in 2020

The Multiple Myeloma (MM) Hub is looking forward to attending the 25th European Hematology Association (EHA) annual congress (EHA25), which will take place in a virtual format June 11–21, 2020. Here, we provide a recap of two major topics from last year, and how we hope to explore them further at the 2020 meeting.

Ensure that you stay up to date with EHA25 by following our Twitter and #EHA25Virtual. The MM Hub will be providing live coverage, articles on key sessions, and interviews with leaders in the myeloma field.

 How to improve frontline treatment in MM?

Firstly, we present to you an interview from the 24th EHA annual congress, where we spoke with the MM Hub Steering Committee (SC) member, Mohamad Mohty, Hôpital Saint-Antoine, Paris, FR. Here, Professor Mohty outlines the positive shift in survival outcomes in the transplant-eligible patient population in recent years, and discusses emerging novel agents, quadruplet induction regimens, and optimal maintenance strategies. Undoubtably, the enhanced understanding of disease pathophysiology has contributed to the refinement of treatment approaches in MM.

This year, we anticipate further information regarding advances in treatment options for both high-risk patients, and those eligible for autologous hematopoietic stem cell transplant. The abstracts to watch out for can be found below.

Quadruplet induction regimens

Elo-VRd

At this year’s meeting, two abstracts will outline the progress surrounding the anti-SLAMF7 monoclonal antibody (mAb), elotuzumab (Elo), and its incorporation into earlier therapeutic intervention. Elo has exhibited favorable clinical activity and safety profiles when combined with immunomodulatory drugs (IMiDs®) or proteasome inhibitors (PIs) in patients with relapsed or refractory MM (RRMM), and has already received approval as a constituent of a number of triplet regimens. The combination of Elo with lenalidomide + dexamethasone (Elo-Rd) and with pomalidamide + dexamethasone (Elo-Pd), for example, have both been approved for the treatment of patients with RRMM. 

However, ongoing studies aim to extend the use of Elo further, consolidating the agent as part of quadruplet induction regimens.

Abstract #S201

Saad Usmani, will be discussing data from the primary analysis of the phase II SWOG-1211 trial (NCT01668719), evaluating bortezomib + Rd (VRd) ± Elo for the treatment of patients with high-risk, newly diagnosed MM (NDMM).

Although this analysis did not uncover a progression-free survival (PFS) benefit of Elo-VRd over VRd, the data support the combination of a PI + IMiD as maintenance therapy for patients with high-risk MM.

Abstract #S203

The second abstract, presented by Hartmut Goldschmidt, University Hospital Heidelberg, DE, illustrates data from the German-speaking Myeloma Multicenter Group HD6 trial (NCT02495922). This study is also evaluating Elo-VRd, but for the treatment of transplant-eligible patients with NDMM.

To date, incorporation of Elo into a VRd induction regimen was not found to improve ≥ very good partial response rates following four cycles of induction therapy in transplant-eligible patients with NDMM. However, in previous studies evaluating Elo, major benefits have been seen at much later follow-ups, and therefore, a final analysis is compulsory to determine the impact of Elo-VRd on PFS and overall survival rates in this setting.

Isa-KRd

Addition of the anti-CD38 mAb, isatuximab (isa), to existing treatment regimens has generated positive clinical outcomes. The phase III ICARIA-MM trial (NCT02990338), for example, reported a clinical activity of isa in combination with Pd vs Pd alone, and the regimen was approved by the U.S. Food and Drug Administration in March 2020, and later by the European Commission in June 2020, for the treatment of RRMM.¹

Abstract #S204

At this year’s EHA meeting, Katja Weisel, is set to present data from the interim analysis of the GMMG-CONCEPT trial (NCT03104842), evaluating the depth of response to isa + carfilzomib + Rd (isa-KRd) in the front-line treatment of high-risk MM. Isa-KRd induction was shown to induce deep responses in patients with high-risk MM; additionally, high rates of measurable residual disease negativity were observed. No new safety concerns were associated with isa-KRd with regard to other anti-CD38 mAbs combined with standard of care regimens.

Isa will also be a highlight in the relapsed setting: the IKEMA interim analysis was selected as a late-breaking abstract for EHA25 (#LB2603), and will be presented by the MM Hub SC member Philippe Moreau. Data from this interim analysis suggest that isa + carfilzomib + dex (isa-Kd) is tolerable in patients with RRMM, and the addition of isa to Kd elicited a greater improvement in PFS and depth of response in these patients. Could isa-Kd represent an emerging standard of care for patients with RRMM?

The MM Hub has been focusing on the ongoing potential of mAbs in MM as an editorial theme, find more information on the agents discussed here.

Maintenance strategies

Prolonged lower-intensity maintenance is an extended strategy that has shown to deepen responses and delay disease progression in patients with MM. Several studies focused on variable induction therapies and embedding maintenance strategies compared with non-maintenance strategies, resulting in improved PFS using the maintenance approach. During the EHA25, studies evaluating the impact of maintenance therapies will be discussed. In particular, ixazomib has demonstrated promising outcomes in patients with MM.

Ixazomib: #S200

The latest results from the phase III TOURMALINE-MM4 study (NCT02312258), led by Meletios A. Dimopoulos, National and Kapodistrian University of Athens, School of Medicine, Athens, GR, will be presented at the EHA25. The randomized, double-blind study was designed to compare the single agent ixazomib maintenance to placebo in patients with NDMM who were not treated with stem cell transplantion. In November 2019, it was announced that the TOURMALINE-MM4 trial had met its primary endpoint of prolonging PFS compared to placebo. Since, it has been declared that ixazomib induces a 34% reduction in the risk of disease progression or death and is well tolerated in patients with NDMM. Expect more data at the EHA25 virtual meeting!

How to overcome resistance to IMiDs in RRMM?

The MM Hub was pleased to talk to Enrique Ocio, Marqués de Valdecilla University Hospital, Santander, ES, at the 24th EHA congress in 2019. Here, the issue of resistance to IMiDs was discussed. While the involvement of cereblon in resistance to IMiDs was highlighted, it was made clear that there are other factors for consideration.

Some of the therapeutic strategies being investigated with the aim to overcome resistance to IMiD-based therapy are to be discussed at the EHA25.

CC-92480: #S208

The MM Hub SC member, Paul Richardson will be presenting data from the first-in-human phase I study (NCT03374085) evaluating the novel cereblon E3 ligase modulator, CC-92480, plus dex for the treatment of RRMM. The phase I portion of this study investigated the safety, tolerability, and pharmacokinetic profile of CC-92480 while also seeking a maximum tolerated dose and recommended phase II dose of CC-92480 + dex, in patients with RRMM.

CC-93269: #S205

The B-cell maturation antigen (BCMA) 2 + 1 T-cell engager, CC-93269, facilitates interaction between T cells and BCMA-expressing MM cells, helping to reinstate immune-mediated tumor destruction.² Results from the interim analysis of a phase I trial (NCT03486067), assessing CC-93269 in patients with RRMM, will be illustrated by Luciano Costa, University of Alabama Comprehensive Cancer Center, Birmingham, US, at this year’s online congress. The MM Hub previously provided a summary of this analysis as presented at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition, read it here. Although ongoing, results from this trial suggest that CC-93269 exhibits a manageable safety profile and promising efficacy.

Teclistamab: #S206

Teclistamab is a humanized BCMA × CD3 bispecific antibody that assists T cell-mediated MM cell cytotoxicity. Teclistamab has demonstrated anti-MM effects in xenograft models, inhibiting tumor growth while also inducing cytokine-mediated T-cell activation.³ At the EHA25, the MM Hub co-chair, María-Victoria Mateos, University Hospital of Salamanca, Salamanca, ES, will present results from the phase I portion of a first-in-human study of teclistamab in patients with RRMM (NCT03145181). At the data cutoff of January 31, 2020, teclistamab exhibited a tolerable safety profile, warranting further evaluation of teclistamab in expansion cohorts.

Ide-cel: #S209

The chimeric antigen receptor (CAR) T-cell therapy stands as a promising treatment option for heavily pretreated patients with MM, with the potential to move into earlier lines of therapy. The BCMA-directed CAR T-cell therapy, idecabtagene vicleucel (ide-cel; BB2121), has demonstrated encouraging tolerability and efficacy in patients with RRMM who have received ≥ 3 prior lines of therapy including an IMiD and a PI, and were refractory to the last line of therapy. At the EHA25, Jesús San Miguel, Universidad de Navarra, Pamplona, ES, will present results from the initial analysis of the pivotal phase II KarMMa study (NCT03361748), investigating ide-cel for the treatment of patients with RRMM. On December 6, 2019, it was announced that the KarMMa study met its primary endpoint of overall response rate and key secondary endpoint of complete response rate; read more on the MM Hub here.

For a comprehensive overview of the status of CAR T-cell therapy in MM, click here.

The MM Hub looks forward to providing further information from the EHA25, ensure that you stay up to date with the latest in MM by following our Twitter!