ASH 2023 Highlight 2
Dr Rutger Callens, a haematologist at AZ Delta in Roeselare, graciously provided key insights into multiple myeloma.
The IsKia EMN24 trial, presented in the plenary session, evaluated the efficacy and safety of isatuximab-carfilzomib-lenalidomide-dexamethasone (IsaKRd) as a pre-autologous stem-cell transplant (ASCT) induction and post-ASCT consolidation compared to KRd in newly diagnosed multiple myeloma patients. The addition of isatuxamab to KRd exhibited significantly higher MRD negativity rates, both post-induction and post-consolidation. Particularly noteworthy was the comparable MRD rates in both the standard risk and very high-risk groups within the ISA-KRd arm, in contrast with the KRd arm.
Given the distinctive mechanisms of action of CAR T cells and T-cell engagers (TCE) in multiple myeloma treatment, a reassessment of conventional prognostic factors, such as MRD, is imperative. A study conducted by a Spanish group revealed that BCMA-directed CAR T yielded approximately twice the MRD negativity rates compared to BCMA-directed TCE. However, once MRD negativity was achieved, the PFS was approximately 20 months in both groups, with MRD-positive patients exhibiting a markedly shorter median PFS of only 3 months.
Several BCMA-directed T-cell engagers are currently under investigation, with two, teclistamab (recently reimbursed in Belgium) and elranatamab, advancing furthest in clinical development. Although no direct comparisons exist, an unanchored matching-adjusted indirect comparison showcased elranatamab’s superior overall response rate and PFS compared to teclistamab in patients with relapsed/refractory multiple myeloma (RRMM).
T-cell engagers, such as talquetamab, present the potential for combination therapies. Talquetamab, a T-cell redirecting bispecific antibody targeting GPRC5D and CD3, combined with the established immunomodulatory drug (IMiD) pomalidomide, demonstrated synergistic antimyeloma effects in the phase 1b MonumenTAL-2 study. Encouragingly, responses were achieved rapidly, with deep and enduring effects. At 6 months, 100% of responders maintained their response, and the median duration of response and PFS were not reached, with 6-month PFS rates hovering around 90%.
Additionally, a phase 1, multicenter, open-label, dose-finding study explored a GPRC5D-targeted autologous CAR T-cell therapy in heavily pretreated and BCMA-exposed RRMM patients. The outcomes revealed profound and persistent responses, including MRD negativity.
In conclusion, the field of multiple myeloma is witnessing ongoing development with the introduction of novel drugs and combinations. MRD negativity rates are on an upward trajectory, and the understanding of when and how to measure MRD negativity is deepening.
References:
Gay F, ASH 2023, #4
Zabaleta A, ASH 2023, #94
Mol I, ASH 2023, #2015
Matous JV, ASH 2023, #1014 Bal S, ASH 2023, #219
With the educational support of:
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