Impact of daratumumab-based induction on stem cell collection parameters in Swedish myeloma patients

Lemonakis, Konstantinos; Tatting, Love; Lisak, Mikael; Carlson, Kristina; Crafoord, Jacob; Blimark, Cecilie; Santamaria, Antonio Izarra; Wichert, Stina; Lenhoff, Stig; Hansson, Markus

doi:10.3324/haematol.2022.281610

Cited by 16 publications

(19 citation statements)

References 14 publications

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“…The mean CD34+ yields after the daratumumab‐containing induction therapy in the CASSIOPEIA trial were significantly lower at 6.7 × 10 6 /kg body weight compared to 10.0 × 10 6 /kg in the VTd arm, 27 thus confirming a previously reported negative effect of anti‐CD38 mAb on stem cells 28 . Both lower CD34+ yields and an increased use of plerixafor in patients undergoing induction with anti‐CD38 mAb were also reported by Lemonakis et al Likewise, in this analysis, most of the patients (88%) underwent chemomobilization with cyclophosphamide 16 . The phase‐II MASTER and GRIFFIN trials also analyzed the use of Daratumumab‐based induction treatment in newly diagnosed and transplant‐eligible MM patients.…”

Section: Discussionsupporting

confidence: 88%

“…12,14,15 However, in this context, the role of prior use of anti-CD38 mAb has not been fully elucidated. The limited data available from the first randomized trials and real-world cohorts describe the efficacy of anti-CD38 mAb in induction therapy and suggest an impaired stem cell yield requiring more frequent need of plerixafor to achieve sufficient stem cell mobilization and collection efficacy, [16][17][18] but in this context, the mobilization modalities have not yet been comparatively analyzed.…”

Section: Introductionmentioning

confidence: 99%

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Steady‐state versus chemotherapy‐based hematopoietic cell mobilization after anti‐CD38‐based induction therapy in newly diagnosed multiple myeloma

Teipel,

Rieprecht,

Trautmann‐Grill

et al. 2023

Transfusion

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BackgroundThe incorporation of anti‐CD38 monoclonal antibodies (mAb) in induction regimens of newly diagnosed transplant‐eligible multiple myeloma (MM) patients has been established as a new standard. However, the optimal strategy of stem cell mobilization in this context is not yet clear.Study Design and MethodsFrom May 2020 till September 2022, we retrospectively reviewed patients receiving anti‐CD38 mAb‐based induction therapy followed by stem cell mobilization either in a steady‐state protocol (SSM) using 10 μg/kg granulocyte colony‐stimulating factor (G‐CSF) for 5 days or in a chemotherapy‐based protocol (CM) using 1–4 g/m2 cyclophosphamide and G‐CSF.ResultsOverall, 85 patients (median age 61 years) were included in the analysis. In total, 90 mobilization attempts were performed, 42 with SSM and 48 with CM. There was no significant difference in the median concentration of CD34+ cells in peripheral blood (PB) prior to apheresis between SSM and CM (61/μL vs. 55.4/μL; p = .60). Cumulative CD34+ yields did not differ between the groups with median of 6.68 and 6.75 × 106/kg body weight, respectively (p = .35). The target yield (≥4 × 106 CD34+ cells/kg body weight) was reached in 88% (CM) and 86% (SSM), with a high proportion even after a single apheresis session (76% vs. 75%).Plerixafor was found to be more frequently used in SSM (52%) than in CM (23%; p < .01). A total of 83 patients underwent autologous transplantation and all were engrafted.ConclusionsStem cell collection in patients undergoing anti‐CD38‐based induction therapy is feasible with either CM or SSM, although SSM more frequently requires plerixafor.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Steady‐state versus chemotherapy‐based hematopoietic cell mobilization after anti‐CD38‐based induction therapy in newly diagnosed multiple myeloma

Teipel,

Rieprecht,

Trautmann‐Grill

et al. 2023

Transfusion

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“…Following cyclophosphamide 2-3 g/m 2 and G-CSF in CASSIOPEIA trial, patients experienced greater use of plerixafor, lower collection of CD34 + cells/kg, and longer intervals to hematologic engraftment after ASCT [4]. Similar results are reported in real-life reports with cyclophosphamide and with chemo-free mobilization approach [5][6][7]. In our experience, higher cyclophosphamide dose 4 g/m 2 together with plerixafor granted optimal stem-cell TA B L E 1 Summary of main reports on patients with multiple myeloma and chronic myeloid leukemia.…”

supporting

confidence: 67%

Daratumumab‐based induction and autologous transplantation in concomitant multiple myeloma and chronic myeloid leukemia

Liberatore,

Fioritoni,

Natale

et al. 2023

eJHaem

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The coexistence of chronic myeloid leukemia (CML) and multiple myeloma (MM) is a rare clinical condition. By means of FISH and molecular analysis on both sorted CD138 plasma cells and cryopreserved CD34 stem cells, a distinct clonal origin of the hematological malignancies was demonstrated in our case. We report on the first patient diagnosed with CML and MM treated with daratumumab, bortezomib, thalidomide, and dexamethasone (Dara‐VTd) induction, stem‐cell collection, and autologous stem cell transplantation (ASCT). The co‐administration of Dara‐VTd and imatinib proved feasible and highly effective in the management of both CML and MM. Despite concerns with stem cell mobilization and collection in patients exposed to daratumumab, in our experience the use of higher cyclophosphamide dose 4 g/m2 together with plerixafor granted optimal stem cell mobilization and collection, irrespective of daratumumab, concomitant myeloid neoplasm, and imatinib. Moreover, ASCT was easily performed with a rapid hematological reconstitution.

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“…132 A real-world analysis in Sweden of NDMM patients found the presence of amp(1q) was independently associated with a shorter OS. 133 In RRMM, subgroup analyses of patients with 1q21+ have been reported for the ICARIA-MM and IKEMA studies investigating isatuximab. 128 In ICARIA-MM, the mPFS in patients with 1q21+ was 9.5 months versus 3.8 months in the Isa-Pd versus Pd arms, respectively (HR = 0.40; 95% CI: 0.25-0.63).…”

Section: Newly Diagnosed MMmentioning

confidence: 99%

Immunomodulatory properties of CD38 antibodies and their effect on anticancer efficacy in multiple myeloma

Bisht,

Fukao,

Chiron

et al. 2023

Cancer Medicine

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BackgroundCD38 has been established as an important therapeutic target for multiple myeloma (MM), for which two CD38 antibodies are currently approved—daratumumab and isatuximab. CD38 is an ectoenzyme that degrades NAD and its precursors and is involved in the production of adenosine and other metabolites.AimAmong the various mechanisms by which CD38 antibodies can induce MM cell death is immunomodulation, including multiple pathways for CD38‐mediated T‐cell activation. Patients who respond to anti‐CD38 targeting treatment experience more marked changes in T‐cell expansion, activity, and clonality than nonresponders.ImplicationsResistance mechanisms that undermine the immunomodulatory effects of CD38‐targeting therapies can be tumor intrinsic, such as the downregulation of CD38 surface expression and expression of complement inhibitor proteins, and immune microenvironment‐related, such as changes to the natural killer (NK) cell numbers and function in the bone marrow niche. There are numerous strategies to overcome this resistance, which include identifying and targeting other therapeutic targets involved in, for example, adenosine production, the activation of NK cells or monocytes through immunomodulatory drugs and their combination with elotuzumab, or with bispecific T‐cell engagers.

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Impact of daratumumab-based induction on stem cell collection parameters in Swedish myeloma patients

Abstract: Not available.

Cited by 16 publications

References 14 publications

Steady‐state versus chemotherapy‐based hematopoietic cell mobilization after anti‐CD38‐based induction therapy in newly diagnosed multiple myeloma

Steady‐state versus chemotherapy‐based hematopoietic cell mobilization after anti‐CD38‐based induction therapy in newly diagnosed multiple myeloma

Daratumumab‐based induction and autologous transplantation in concomitant multiple myeloma and chronic myeloid leukemia

Immunomodulatory properties of CD38 antibodies and their effect on anticancer efficacy in multiple myeloma

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