High dose (conditioning) regimens used prior to autologous stem cell transplantation in multiple myeloma

Ali, Mohammad; Hadidi, Samer Al

doi:10.1016/j.jtct.2022.06.013

Cited by 9 publications

(3 citation statements)

References 57 publications

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“…Melphalan at 200 mg/m 2 is currently the standard HDCT regimen for younger MM patients [24,25]. For patients over the age of 65 or with renal impairment, a dose reduction in melphalan to 140 mg/m 2 is recommended [24]. A randomized phase III study compared the efficacy and safety of melphalan 200 mg/m 2 to BuMel.…”

Section: Discussionmentioning

confidence: 99%

“…Conditioning with BuMel led to improvement in PFS (64.7 vs. 43.5 months, p = 0.022) but was associated with a significantly higher mucositis rate (74% vs. 14%) [23]. Further combinations with other drugs, including BCNU, cyclophosphamide, mitoxantrone, topotecan, and bortezomib, have been explored within small patient cohorts in several phase I/II studies, as well as retrospective studies [24]. Moreover, another phase III study compared tandem high-dose melphalan with total-marrow irradiation, busulfan, and cyclophosphamide (TMI/Bu/Cy).…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and Safety of High-Dose Chemotherapy with Treosulfan and Melphalan in Multiple Myeloma

Gillich,

Akhoundova,

Hayoz

et al. 2023

Cancers

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(1) Background: Upfront treatment consolidation with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) has relevantly contributed to achieving durable remissions following induction treatment in multiple myeloma (MM) patients. The optimization of HDCT regimens can, therefore, essentially contribute to improving the depth and duration of tumor remissions. To date, melphalan at 200 mg/m2 is the standard HDCT regimen for fit MM patients. In our previous work, we showed promising efficacy and safety results for treosulfan (14 g/m2) and melphalan (200 mg/m2) (TreoMel) in acute myeloid leukemia (AML) patients receiving ASCT. Based on these data, TreoMel became the standard of care for fit MM patients at our institution. (2) Methods: We identified 115 consecutive MM patients who underwent consolidation with TreoMel between 01/2020 and 08/2022 at the University Hospital of Bern. We analyzed the safety and efficacy data, as well as the treosulfan pharmacokinetics, correlating them with tumor responses. (3) Results: A complete response (CR) rate of 84% was achieved, which is comparable to the CR rate reported for the quadruplet combination. The median PFS was 30 months (95% CI: 20.4—not reached), and the 31-month OS rate was 83%. The median area under the curve (AUC) for treosulfan was 952.5 mg*h/L (range: 527.4–1781.4), and the median peak level was 332.3 mg/L (range: 168–554). The treosulfan pharmacokinetics showed no significant correlation with MM responses after HDCT and ASCT. However, female patients had a significantly higher AUC (p = 0.007) and peak value (p = 0.001), and the higher values were associated with longer hospitalizations. (4) Conclusions: Treatment consolidation with TreoMel HDCT demonstrated a promising efficacy and safety profile in our cohort of MM patients and deserves further investigation in prospective studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of High-Dose Chemotherapy with Treosulfan and Melphalan in Multiple Myeloma

Gillich,

Akhoundova,

Hayoz

et al. 2023

Cancers

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“…Older patients often presented with poor prognostic factors and had several comorbidities which limited the selection of treatment. At present, ASCT remains the standard treatment after induction therapy for eligible patients with newly diagnosed MM [15]. Barlogie B et al [16] randomly enrolled 516 MM patients, 261 of whom received ASCT and 255 of whom received standard dose chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Characteristics and Risk Factors of Ultra-High-Risk Patients with Newly Diagnosed Multiple Myeloma

Geng

Yang

Zhou

et al. 2023

JPM

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Objective: To investigate the clinical characteristics and risk factors of ultra-high-risk (UHR) patients with newly diagnosed multiple myeloma (MM). Methods: We screened UHR patients with a survival of less than 24 months and we selected patients with a concurrent survival of more than 24 months as a control group. We retrospectively analyzed the clinical characteristics of UHR patients with newly diagnosed MM and screened related risk factors. Results: In total we analyzed 477 patients, which included 121 (25.4%) UHR patients and 356 (74.6%) control patients. Median overall survival (OS) and progression-free survival (PFS) of UHR patients was 10.5 months (7.5–13.5 months) and 6.3 months (5.4–7.2 months), respectively. Univariate logistic regression analysis showed that age > 65 years, hemoglobin (HGB) < 100 g/L, lactate dehydrogenase (LDH) > 250 U/L, serum creatinine (SCr) > 2 mg/dL, corrected serum calcium (CsCa) > 2.75 mmol/L, B-type natriuretic peptide (BNP) or N-terminal prohormone BNP (NT-proBNP) > 2 upper limit of normal (ULN), high-risk cytogenetics, Barthel index score, and International Staging System (ISS) stage III were associated with UHR MM. In a multivariate analysis, age > 65 years, LDH > 250 U/L, CsCa > 2.75 mmol/L, BNP or NT-proBNP > 2 ULN, high-risk cytogenetics, and Barthel index score were independent risk factors for UHR MM. Moreover, UHR patients had a worse response rate than control patients. Conclusion: Our study highlighted the characteristics of UHR MM patients and suggested that the combination of organ insufficiency and highly malignant myeloma cells resulted in poor outcomes of patients with UHR MM.

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Assessing Outcomes in Patients With Multiple Myeloma Postautologous Stem Cell Transplantation: Contrasting the Effects of Melphalan Dosages at 200 mg/m2 versus 140 mg/m2

Brown,

Scott,

Zhang

et al. 2024

Clinical Lymphoma Myeloma and Leukemia

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High dose (conditioning) regimens used prior to autologous stem cell transplantation in multiple myeloma

Cited by 9 publications

References 57 publications

Efficacy and Safety of High-Dose Chemotherapy with Treosulfan and Melphalan in Multiple Myeloma

Efficacy and Safety of High-Dose Chemotherapy with Treosulfan and Melphalan in Multiple Myeloma

Characteristics and Risk Factors of Ultra-High-Risk Patients with Newly Diagnosed Multiple Myeloma

Assessing Outcomes in Patients With Multiple Myeloma Postautologous Stem Cell Transplantation: Contrasting the Effects of Melphalan Dosages at 200 mg/m2 versus 140 mg/m2

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