Transplant-ineligible newly diagnosed multiple myeloma: Current and future approaches to clinical care: A Young International Society of Geriatric Oncology Review Paper

Grant, Shakira J.; Mian, Hira; Giri, Smith; Boutin, Melina; Dottorini, Lorenzo; Neuendorff, Nina Rosa; Krok‐Schoen, Jessica L.; Nikita, Nikita; Rosko, Ashley; Wildes, Tanya M.

doi:10.1016/j.jgo.2020.12.001

Cited by 8 publications

(7 citation statements)

References 73 publications

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“…The patients' other demographic and laboratory details are described in Table 1 (additional details are given in Supporting Information S1: Table S5 ). Of 141, 45 patients were transplant‐ineligible as per standard criteria, 40 , 41 and the remaining 96 patients were planned for therapy without ASCT due to patient preference or resource constraints, or logistic issues. Ninety‐eight of 141 patients received VCd (bortezomib, cyclophosphamide, dexamethasone)‐based therapy and 43 of 141 received VRd (bortezomib, lenalidomide, dexamethasone)‐based therapy depending on patients' clinical status and financial conditions.…”

Section: Resultsmentioning

confidence: 99%

Circulating tumor plasma cells and peripheral blood measurable residual disease assessment in multiple myeloma patients not planned for upfront transplant

Tembhare,

Sriram,

Khanka

et al. 2024

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Circulating tumor plasma cells (CTPCs) provide a noninvasive alternative for measuring tumor burden in newly diagnosed multiple myeloma (NDMM). Moreover, measurable residual disease (MRD) assessment in peripheral blood (PBMRD) can provide an ideal alternative to bone marrow MRD, which is limited by its painful nature and technical challenges. However, the clinical significance of PBMRD in NDMM still remains uncertain. Additionally, data on CTPC in NDMM patients not treated with transplant are scarce. We prospectively studied CTPC and PBMRD in 141 NDMM patients using highly sensitive multicolor flow cytometry (HS‐MFC). PBMRD was monitored at the end of three cycles (PBMRD1) and six cycles (PBMRD2) of chemotherapy in patients with detectable baseline CTPC. Patients received bortezomib‐based triplet therapy and were not planned for an upfront transplant. Among baseline risk factors, CTPC ≥ 0.01% was independently associated with poor progression‐free survival (PFS) (hazard ratio [HR] = 2.77; p = 0.0047) and overall survival (OS) (HR = 2.9; p = 0.023) on multivariate analysis. In patients with detectable baseline CTPC, undetectable PBMRD at both subsequent time points was associated with longer PFS (HR = 0.46; p = 0.0037), whereas detectable PBMRD at any time point was associated with short OS (HR = 3.25; p = 0.004). Undetectable combined PBMRD (PBMRD1 and PBMRD2) outperformed the serum‐immunofixation‐based response. On multivariate analysis, detectable PBMRD at any time point was independently associated with poor PFS (HR = 2.0; p = 0.025) and OS (HR = 3.97; p = 0.013). Thus, our findings showed that CTPC and PBMRD assessment using HS‐MFC provides a robust, noninvasive biomarker for NDMM patients not planned for an upfront transplant. Sequential PBMRD monitoring has great potential to improve the impact of the existing risk stratification and response assessment models.

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Section: Resultsmentioning

confidence: 99%

Circulating tumor plasma cells and peripheral blood measurable residual disease assessment in multiple myeloma patients not planned for upfront transplant

Tembhare,

Sriram,

Khanka

et al. 2024

HemaSphere

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“…Recommendations for lon gi tu di nal assessments of ft ness and frailty have been based on con sen sus expert opin ion. [17][18][19] Although these ft ness/frailty scores have shaped our under stand ing of the het ero ge ne ity among older adults with mye loma, the appli ca tion of such scores in the clin i cal set ting requires con sid er ation of other fac tors such as patient pref erences, life expec tancy, and dis ease biol ogy.…”

Section: Rationale For Con Sid Er Ing Nontransplant Strat E Gies In O...mentioning

confidence: 99%

“…The lat est update of the MAIA study reported an esti mated 48-month PFS of 60%. 22 There are numer ous nontransplant reg i mens 19,23,24 ; other alter na tives could include daratumumab, bortezomib, melphalan, prednisone (D-VMP); borezomib, lenalidomide, dexamethasone (VRD); cyclophosphadmide, bortezomib, dexamethasone (CyborD). The most com mon induc tion strat egy for those aged less than 65 to 74 years, in the United States, is VRD front line ther apy.…”

Section: Rationale For Con Sid Er Ing Nontransplant Strat E Gies In O...mentioning

confidence: 99%

Treatment of older adult or frail patients with multiple myeloma

2021

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Older adults with multiple myeloma (MM) are a growing population, and personalizing treatment based on disease and health status is imperative. Similar to MM staging systems that provide disease-related prognostic information, myeloma-specific frailty tools can better identify subgroups at greatest risk for treatment-related toxicity and early treatment discontinuation, as well as predict overall survival. Several myeloma-specific validated tools are well studied. Although these fitness/frailty scores have shaped our understanding of the heterogeneity among older adults with myeloma, the application of such scores in treatment decision making (ie, transplant considerations, relapse) is an unmet need. Here we outline how to incorporate frailty assessments in the evaluation of older adults with MM in the clinical setting with consideration of other factors such as patient preferences, treatment risks/benefits, life expectancy, and disease biology.

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“…Patients who are not candidates for transplant are treated with 8-12 cycles of VRd, followed by lenalidomide maintenance. Alternative regimens include daratumumab, lenalidomide, dexamethasone (DRd) or daratumumab, bortezomib, melphalan, and prednisolone (D-VMP) [3,[14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Introductory Chapter: Update on Multiple Myeloma

Al-Anazi¹

2023

Recent Updates on Multiple Myeloma

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extra-hematological toxicity, and the brief period of neutropenia [24,25]. Outpatient HSCT has certain inclusion criteria and exclusion criteria as well as several advantages that include: significant reduction in costs; saving hospital beds; lower rate of infections; and lower morbidity and treatment-related mortality [24,[26][27][28].In patients with MM, maintenance therapy after autologous HSCT has been shown to deepen and prolong responses and increase OS and progression-free survival (PFS) [29]. Lenalidomide maintenance given after autologous HSCT till disease progression is the standard of care in patients with SR MM while bortezomib maintenance therapy after autologous HSCT is preferable in MM patients having: HR cytogenetics, renal insufficiency, inability to tolerate lenalidomide, and previous history of another cancer [30][31][32]. Continuous therapy has been shown to significantly improve OS and PFS [33,34]. Continuous therapy till disease progression has become a key strategy in the treatment of patients with MM as it has been shown to improve duration of remission and it represents the standard approach for patients with MM both at diagnosis and at relapse [35,36].Unfortunately, nearly all MM patients ultimately relapse, even those who experience a complete response (CR) to initial therapy [19]. Management of the relapsed disease remains a critical aspect of MM care and an important area of ongoing research [19]. New treatment strategies and therapeutic modalities are needed to treat MM in relapse, particularly in case of triple-refractory disease [1]. Treatment of relapsed MM should depend on: the number of relapses encountered; the previous anti-myeloma treatment; the presence of de novo or acquired drug resistance; aggressiveness of disease relapse particularly in case of extramedullary disease, plasma cell leukemia, or clonal evolution [3,37].Minimal residual disease (MRD) is an important factor that can independently predict the prognosis of MM during treatment as undetectable MRD has been shown to improve PFS and OS regardless: disease status, prior transplant, or cytogenetic risk [38]. Flow cytometry has become a valuable tool to monitor MRD and evaluate the depth of CR. However, next-generation flow cytometry is more sensitive than the standard flow cytometry in detecting MRD in patients with MM [39]. Finally, the development of novel targeting therapies with different mechanisms of action is needed to achieve deep and durable responses in an attempt to cure MM while identification of tumor intrinsic and extrinsic resistance mechanisms may direct the design of combinations of novel drugs that prevent or overcome drug resistance so as to improve patient survival [40,41].

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Transplant-ineligible newly diagnosed multiple myeloma: Current and future approaches to clinical care: A Young International Society of Geriatric Oncology Review Paper

Cited by 8 publications

References 73 publications

Circulating tumor plasma cells and peripheral blood measurable residual disease assessment in multiple myeloma patients not planned for upfront transplant

Circulating tumor plasma cells and peripheral blood measurable residual disease assessment in multiple myeloma patients not planned for upfront transplant

Treatment of older adult or frail patients with multiple myeloma

Introductory Chapter: Update on Multiple Myeloma

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