Limited efficacy of daratumumab in multiple myeloma with extramedullary disease

Jelı́nek, Tomáš; Ševčíková, Tereza; Žihala, David; Popková, Tereza; Kapustová, Veronika; Broskevičová, Lucie; Čápková, Lenka; Říhová, Lucie; Bezděková, Renata; Ševčı́ková, Sabina; Židlík, Vladimír; Havel, Martin; Plonková, Hana; Jungová, Alexandra; Minařík, Jiří; Štork, Martin; Pour, Luděk; Pavlíček, Petr; Špıčka, Ivan; Maisnar, Vladimír; Radocha, Jakub; Šimíček, Michal

doi:10.1038/s41375-021-01343-w

Cited by 32 publications

(29 citation statements)

References 14 publications

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“…Similarly, ixazomib did not show significant improvement of secondary EMD prognosis in real‐life analysis 29 . Anti‐CD38 antibodies (daratumumab, isatuximab) have not overcome poor prognosis of secondary EMD, possibly due to low expression of the CD38 surface antigen in EMD PCs 30,31 . A much lower response rate was also shown in a subset of EMD patients treated with the anti‐BCMA (B cell maturation antigen) drug conjugate belantamab 32 .…”

Section: Discussionmentioning

confidence: 99%

“… 29 Anti‐CD38 antibodies (daratumumab, isatuximab) have not overcome poor prognosis of secondary EMD, possibly due to low expression of the CD38 surface antigen in EMD PCs. 30 , 31 A much lower response rate was also shown in a subset of EMD patients treated with the anti‐BCMA (B cell maturation antigen) drug conjugate belantamab. 32 Preliminary results of the peptide–drug conjugate melphalan flufenamide (melflufen) in a heavily pretreated cohort of secondary EMD patients seem promising, but longer follow‐up is necessary.…”

Section: Discussionmentioning

confidence: 99%

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Identification of patients at high risk of secondary extramedullary multiple myeloma development

et al. 2021

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Multiple myeloma (MM) is characterized by malignant plasma cell infiltration of the bone marrow. In extramedullary multiple myeloma (EMD), a subclone of these cells migrates out of the bone marrow. Out of 4 985 MM patients diagnosed between 2005 and 2017 in the Czech Republic, we analyzed 234 secondary EMD patients to clarify risk factors of secondary EMD development. We found younger age [<65 years; odds ratio (OR) 4Á38, 95% confidence interval (CI): 2Á46-7Á80, P < 0Á0001], high lactate dehydrogenase (LDH) levels (>5 lkat/l; OR 2Á07, 95% CI: 1Á51-2Á84, P < 0Á0001), extensive osteolytic activity (OR 2Á21, 95% CI: 1Á54-3Á15, P < 0Á001), and immunoglobulin A (IgA; OR 1Á53, 95% CI: 1Á11-2Á11, P = 0Á009) or the non-secretory type of MM (OR 2Á83; 95% CI: 1Á32-6Á04, P = 0Á007) at the time of MM diagnosis to be the main risk factors for secondary EMD development. Newly diagnosed MM (NDMM) patients with subsequent EMD had inferior median progression-free (PFS) and overall (OS) survival when compared to NDMM patients without future EMD [mPFS: 13Á8 months (95% CI: 11Á4-16Á3) vs 18Á8 months (95% CI: 17Á7-19Á9), P = 0Á006; mOS: 26Á7 months (95% CI: 18Á1-35Á4) vs 58Á7 months (95% CI: 54Á8-62Á6), P < 0Á001]. We found that NDMM patients with specific risk factors associated with secondary EMD development have a more aggressive disease course before secondary EMD develops.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of patients at high risk of secondary extramedullary multiple myeloma development

et al. 2021

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“…In the context of daratumumab therapy, the CASSIOPET study, the PET/CT companion study of the CASSIOPEIA trial, showed that more patients reached PET/CT negativity in the Daratumumab-VTD (Bortezomib, Thalidomide, Dexamethasone) arm than in the VTD arm [26]. However, Daratumumab does not seem to be able to counteract the poor prognosis of the extramedullary disease [27]. Overall, to our knowledge, few studies have looked at the correlation between PET/CT and the response to anti-CD38 treatment.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of FDG-PET/CT Parameters in Patients with Relapse/Refractory Multiple Myeloma before Anti-CD38 Based Therapy

Fouquet

Dechmi

Willems

et al. 2021

Cancers

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Although anti-CD38 monoclonal antibodies have improved the prognosis of relapsed/refractory multiple myeloma (RRMM), some patients still experience early relapses with poor outcomes. This present study evaluated the predictive value of FDG PET/CT parameters for RRMM prior to initiating anti-CD38 treatment. We included 38 consecutive RRMM patients who underwent a PET/CT scan treated at our institution at relapse. The median PFS was 12.5 months and the median OS was not reached. 42% of the patients had an initial ISS score of 1, 37% of 2, and 21% of 3. The presence of >3 focal lesions (FLs, n = 19) and the ISS score were associated with inferior PFS (p = 0.0036 and p = 0.0026) and OS (p = 0.025 and p = 0.0098). Patients with >3 FLs had a higher initial ISS score (p = 0.028). In multivariable analysis, the ISS score and >3 FLs were independent prognostic factors for PFS (p = 0.010 and p = 0.025 respectively), and combined they individualized a high-risk group with a median PFS and OS of 3.1 months and 8.5 months respectively vs. not reached for the other patients. The presence of >3 FLs on PET was predictive of survival outcomes in patients with RRMM treated using CD38 targeted therapy. Combined with the initial ISS, an ultra-high-risk RRMM population can thus be identified.

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“…Daratumumab showed limited efficacy in EMD and this phenomenon can be explained by decreased CD38 expression on extramedullary PCs [38] . A real-world retrospective study revealed modest efficacy of single-agent daratumumab in 41 RRMM patients, including 32% of patients with EMD.…”

Section: Monoclonal Antibodies Targeting Cd38mentioning

confidence: 99%

Advances in the treatment of extramedullary disease in multiple myeloma

Sun

2022

Translational Oncology

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Limited efficacy of daratumumab in multiple myeloma with extramedullary disease

Cited by 32 publications

References 14 publications

Identification of patients at high risk of secondary extramedullary multiple myeloma development

Identification of patients at high risk of secondary extramedullary multiple myeloma development

Prognostic Value of FDG-PET/CT Parameters in Patients with Relapse/Refractory Multiple Myeloma before Anti-CD38 Based Therapy

Advances in the treatment of extramedullary disease in multiple myeloma

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