The clinical course and life expectancy of patients with multiple myeloma who discontinue their first daratumumab‐containing line of therapy

Szabo, Agoston Gyula; Thorsen, Jonathan; Iversen, Katrine Fladeland; Levring, Mette Bøegh; Preiss, Birgitte; Helleberg, Carsten; Breinholt, Marie Fredslund; Hermansen, Emil; Gjerdrum, Lise Mette Rahbek; Bønløkke, Søren Thorgaard; Nielsen, Katrine; Kjeldsen, Eigil; Teodorescu, Elena Manuela; Dokhi, Marveh; Kurt, Eva; Strandholdt, Casper Nørgaard; Andersen, Mette Klarskov; Vangsted, Annette Juul

doi:10.1002/ajh.26449

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…The methods of data generation for this project have been previously described [19,20]. In short, we conducted a nationwide retrospective review of the clinical course of all patients treated with a daratumumab-containing regimen prior to January antibodies were used).…”

Section: Methodsmentioning

confidence: 99%

“…However, none of the above studies were performed specifically in patients with previous CD38 antibody exposure, and the clinical performance of pomalidomide in the era of CD38 antibodies is unknown. We have previously reported results from a complete Danish, nationwide cohort of daratumumab‐exposed patients [19, 20]. The aim of this current study was to describe the real‐world use and efficacy of pomalidomide in this cohort.…”

Section: Introductionmentioning

confidence: 99%

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The real‐world use and efficacy of pomalidomide for relapsed and refractory multiple myeloma in the era of CD38 antibodies

Szabo,

Thorsen,

Iversen

et al. 2023

eJHaem

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Pomalidomide‐dexamethasone (Pd) has been a standard care treatment for relapsed and refractory multiple myeloma since 2013. However, the outcomes of Pd after exposure to CD38 antibodies are not known. Here we describe the real‐world use and efficacy of pomalidomide in a Danish, nationwide cohort of daratumumab‐exposed patients. We identified 328 patients that were treated with pomalidomide. Of these, 137 received Pd, 65 daratumumab‐pomalidomide‐dexamethasone (DPd), 43 pomalidomide‐cyclophosphamide‐dexamethasone (PCd), 19 carfilzomib‐pomalidomide‐dexamethasone (KPD), 11 pomalidomide‐bortezomib‐dexamethasone (PVd), and 52 pomalidomide in other combinations. Patients treated with Pd in this cohort had a partial response or better (≥ PR) rate of 35.8% and median time to next treatment (mTNT) of 4.9 months, almost identical to the results of previous prospective clinical trials. Although treatment with the various pomalidomide‐containing triplet regimens resulted in higher ≥ PR rates (PCd: 46.5%, PVd: 63.6%, DPd: 55.4%, KPd: 63.2%), the mTNT achieved was not significantly better than with Pd in most cases (PCD: 5.4, PVD: 5.3, DPD: 4.7 months). The exception to this was KPd (mTNT 7.4 months), but this regimen was mainly used earlier in the course of the disease (median time from diagnosis 2.3 years vs. 3.7–4.3 years). The most important predictor of outcomes was not the choice of index regimen (p = 0.72), but prior exposure (p = 0.0116). Compared to CD38 antibody‐naïve patients, triple‐class‐exposed patients achieved reduced ≥ PR rate (38.0% vs. 47.3%), shorter mTNT (4.0 vs. 5.9 months), and shorter median overall survival (12.4 vs. 24.2 months) with pomalidomide treatment.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The real‐world use and efficacy of pomalidomide for relapsed and refractory multiple myeloma in the era of CD38 antibodies

Szabo,

Thorsen,

Iversen

et al. 2023

eJHaem

Self Cite

View full text Add to dashboard Cite

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Role of daratumumab in the frontline management of multiple myeloma: a narrative review

Yadav,

Gundeti,

Bhave

et al. 2023

Expert Review of Hematology

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Extracellular Vesicles Isolated from Plasma of Multiple Myeloma Patients Treated with Daratumumab Express CD38, PD-L1, and the Complement Inhibitory Proteins CD55 and CD59

Brennan

Iversen

Blanco-Fernández

et al. 2022

Cells

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Daratumumab (DARA) has improved the outcome of treatment of multiple myeloma (MM). DARA acts via complement-dependent and -independent mechanisms. Resistance to DARA may result from upregulation of the complement inhibitory proteins CD55 and CD59, downregulation of the DARA target CD38 on myeloma cells or altered expression of the checkpoint inhibitor ligand programmed death ligand-1 (PD-L1) or other mechanisms. In this study, EVs were isolated from peripheral blood (PB) and bone marrow (BM) from multiple myeloma (MM) patients treated with DARA and PB of healthy controls. EV size and number and the expression of CD38, CD55, CD59 and PD-L1 as well as the EV markers CD9, CD63, CD81, CD147 were determined by flow cytometry. Results reveal that all patient EV samples express CD38, PD-L1, CD55 and CD59. The level of CD55 and CD59 are elevated on MM PB EVs compared with healthy controls, and the level of PD-L1 on MM PB EVs is higher in patients responding to treatment with DARA. CD147, a marker of various aspects of malignant behaviour of cancer cells and a potential target for therapy, was significantly elevated on MM EVs compared with healthy controls. Furthermore, mass spectrometry data suggests that MM PB EVs bind DARA. This study reveals a MM PB and BM EV protein signatures that may have diagnostic and prognostic value.

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The clinical course and life expectancy of patients with multiple myeloma who discontinue their first daratumumab‐containing line of therapy

Cited by 3 publications

References 6 publications

The real‐world use and efficacy of pomalidomide for relapsed and refractory multiple myeloma in the era of CD38 antibodies

The real‐world use and efficacy of pomalidomide for relapsed and refractory multiple myeloma in the era of CD38 antibodies

Role of daratumumab in the frontline management of multiple myeloma: a narrative review

Extracellular Vesicles Isolated from Plasma of Multiple Myeloma Patients Treated with Daratumumab Express CD38, PD-L1, and the Complement Inhibitory Proteins CD55 and CD59

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