Recent Advances in Multiple Myeloma (ASH 2021)

Recent Advances in Multiple Myeloma (ASH 2021)

Data that was released during the American Society of Hematology (ASH) 2021 meeting represents significant progress in the field and will have a positive impact on patients’ lives. Below are a few of the key trials generating excitement and representing advances in the treatment of multiple myeloma (MM).

[FERMA.AI facilitated the analysis of the over 4,800 abstracts presented at this year’s ASH meeting as well as the identification of key data in MM.]

What is generating excitement in multiple myeloma?

Highlights include the expanding body of evidence supporting both allogeneic and autologous CAR T-cell therapy, preliminary results from a trial assessing a first-in-class bispecific antibody directed against a novel MM target, and key data supporting the use of three new BCMAxCD3 bispecific antibodies.

Allogeneic CAR T-cell therapy

ALLO-715 is an allogeneic anti-B cell maturation antigen (BCMA) CAR T-cell therapy being developed by Allogene Therapeutics. Donor-derived allogeneic CAR T-cell therapies like ALLO-715 that are available off-the-shelf hold a key advantage over autologous CAR T-cell therapies that need to be manufactured from each individual patient’s T-cells in a costly and time-consuming process. However, autologous CAR T-cell therapies have historically shown greater efficacy in clinical trials for MM. In results read out from its Phase 1 trial, ALLO-715 was the first allogeneic anti-BCMA CAR T-cell therapy to demonstrate substantial efficacy in MM, with a 71% overall response rate (ORR) comparable to approved autologous CAR-T cell therapies. It has the potential to address significant unmet need, especially in patients with rapidly progressive disease who would benefit from an off-the-shelf therapy.

Autologous CAR T-cell therapy

Janssen’s ciltacabtagene autoleceul (cilta-cel) is a BCMA-directed autologous CAR T-cell therapy administered as a single infusion. At a median follow-up of 2 years, a Phase 1/2 study of cilta-cel reported deep and durable responses along with a survival benefit (ORR: 98%; PFS: 60.5%; OS: 74.0%), supporting the further development of cilta-cel as an important treatment option for MM.

Efficacy response of ciltacabtagene autoleceul. Source: ASH21

A first-in-class bispecific antibody

Janssen announced results from its first-in-human Phase 1b investigation of talquetamab, the only off-the-shelf T-cell redirecting bispecific antibody in development targeting GPRC5D (a novel target in MM) and CD3 on T-cells, in combination with Darzalex (daratumumab). The preliminary data suggested a promising ORR of 77-85% in heavily pretreated relapsed/refractory MM patients, providing evidence for this novel immunotherapy-based treatment approach.

ORR from TRIMM-2 for talquetamab in combination with daratumumab. Source: ASH21

BCMAxCD3 bispecific antibodies

Three key studies highlighted early data from clinical trials for BCMAxCD3 bispecific antibodies, with encouraging results supporting further development.

Regeneron presented data supporting REGN-5458 which is currently in Phase 1/2 development. In its first-in-human study, investigators found an ORR of 75% in a patient population that had previously received a median of 5 lines of therapy.

In its first-in-human Phase 1 study, AbbVie’s TNB-383B demonstrated promising efficacy with an 81% ORR in relapsed/refractory MM patients who had received at least 3 prior lines of therapy.

Finally, Janssen shared results from its Phase 1/2 trial for teclistamab in triple-class exposed relapsed/refractory MM. Preliminary data showed a 62% ORR with responses that were durable and that deepened over time.

Phase 1 efficacy of REGN-5458. Source: ASH21

Moving forward

Over the next few years, a number of revolutionary treatment options are likely to be approved for the highly concentrated multiple myeloma market. The preliminary data released at ASH 2021 suggests encouraging efficacy for a variety of CAR T-cell therapies and distinct MOAs.

We will be watching the market to better understand how physicians will utilize these valuable therapies and the benefits they will bring to a patient population with high unmet need.

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