Bortezomib-based consolidation or maintenance therapy for multiple myeloma: a meta-analysis

Zhang, Shijia; Kulkarni, Amit; Xu, Beibei; Chu, Haitao; Kourelis, Taxiarchis; Go, Ronald S.; Wang, Michael L.; Bachanová, Veronika; Wang, Yucai

doi:10.1038/s41408-020-0298-1

Cited by 26 publications

(20 citation statements)

References 35 publications

(66 reference statements)

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“…The consensus of the Mayo Clinic recommends: immunomodulators maintenance for patients with standard-risk cytogenetics and PI maintenance therapy for patients with high-risk cytogenetics ( 16 ). Data from our center revealed that compared with thalidomide and lenalidomide, PFS and OS can both benefit from bortezomib-based regimens (median PFS: 43.7 vs 38.5 months; median OS: not reached vs 78.5 months), findings consistent with the reported literature ( 18 ). It is worth noting that in the phase III HOVON-65/GMMG-HD4 trial, the early research report showed that OS was superior after bortezomib-based regimens for induction and maintenance compared to non–bortezomib-based regimen inductions and thalidomide maintenance therapy ( 19 ).…”

Section: Discussionsupporting

confidence: 90%

“…Clinic`al trial data have shown that bortezomib consolidation after ASCT only improved the PFS of patients not achieving at least VGPR, had no effect on patients who achieved at least VGPR, and did not prolong OS in both categories of patients ( 23 ). Consolidation therapy refers to the utilization of a short course of treatment to reduce the number of residual tumor cells, which can prolong PFS but not OS ( 18 ). Consolidation and maintenance therapy play a different role in patients’ outcomes.…”

Section: Discussionmentioning

confidence: 99%

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Different Patient Subgroup Different Maintenance, Proteasome Inhibitors or Immunomodulators Maintenance for Newly Diagnosed Multiple Myeloma: A 7-Year Single-Center Data in China

et al. 2021

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IntroductionWe analyzed different patient subgroups to determine optimal maintenance therapy in newly diagnosed multiple myeloma (NDMM) patients.MethodsA total of 226 NDMM patients in our center were included in the study. The characteristics, survival, and adverse reactions were compared among patients who received maintenance therapy or not, and patients who received proteasome inhibitors (PIs) or immunomodulators (IMiDs) maintenance. The survival of different maintenance durations of bortezomib-based regimens was also analyzed.ResultsThe maintenance therapy not only upgraded more patient responses (34.3 vs 13.3%, P = 0.006), but also significantly prolonged their progression-free survival (PFS) (median PFS: 41.1 vs 10.5 months, P < 0.001) and overall survival (OS) (median OS: not reached vs 38.6 months, P < 0.001). Compared with IMiDs, the PFS (median PFS: 43.7 vs 38.5 months, P = 0.034) and OS (median OS: not reached vs 78.5 months, P = 0.041) were both enhanced by PIs maintenance. Patients younger than 65 years who received PIs had a significantly prolonged OS (P = 0.032). Patients achieving only a partial response (PR) after induction and consolidation therapy had significantly longer PFS and OS after PIs maintenance compared to IMiDs (P = 0.007, 0.002). High-risk patients (ISS 2–3, DS 2–3, and RISS 2–3) given PIs maintenance benefit from a prolonged PFS (P = 0.002, 0.02, 0.06) and OS (P = 0.059, 0.047, 0.044, respectively) compared with IMiDs therapy. OS was significantly prolonged in patients who received ≥ 12 months of bortezomib-based maintenance therapy compared to those who were treated for < 12 months (P < 0.001), but no difference was observed in OS between patients who received 12 to 24 or ≥ 24 months of bortezomib-based maintenance therapy (P = 0.292).ConclusionPIs maintenance was superior to IMiDs in overall PFS and OS. The beneficial effect was most evident in patients achieving PR after induction and consolidation therapy, and in high-risk patients. Moreover, younger patients also benefited from PIs maintenance with an increased OS. A bortezomib-based maintenance therapy duration of 12 to 24 months after induction and consolidation therapy produced satisfactory OS.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Different Patient Subgroup Different Maintenance, Proteasome Inhibitors or Immunomodulators Maintenance for Newly Diagnosed Multiple Myeloma: A 7-Year Single-Center Data in China

et al. 2021

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“…As the consensus of Mayo Clinic recommends: immunomodulators maintenance is recommended for patients with standard-risk cytogenetics, meanwhile, PI maintenance for high-risk cytogenetics [16]. Data from our center revealed that compared with thalidomide and lenalidomide, the PFS and OS can both bene t from bortezomib-based regimens (median PFS: 43.7 vs. 38.5 months; median OS: not reached vs. 78.5 months), which was consistent with the literature [18]. It is worth noting that in the phase III HOVON-65/GMMG-HD4 trial the early research report showed the OS was superior in bortezomib-based regimens induction and maintenance arm to non-bortezomib-based regimens induction and thalidomide maintenance arm [19], however, after long-term follow-up, the OS was no difference between two arms, due to the majority of patients have relapsed inevitably and received multiple effective post-relapse treatments [20].…”

Section: Discussionsupporting

confidence: 88%

“…Clinal trial research showed that bortezomib consolidation after ASCT only improved the PFS of patients not achieving at least VGPR, no effect on patients who achieved at least VGPR, and did not prolong OS in both category patients [23]. Consolidation therapy refers to utilize a short course of treatment for reducing the number of residual tumor cells, which cloud prolonged the PFS but not OS [18]. Consolidation and maintenance play a different role in patients' outcomes.…”

Section: Discussionmentioning

confidence: 99%

Proteasome Inhibitor or Immunomodulators Which is The Optimal Maintenance For Newly Diagnosed Multiple Myeloma: A 7-Year Real-World Data in China.

Han

Jin

Zheng

et al. 2021

Preprint

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Background: According to different patients’ subgroups choose optimal maintenance therapy. Methods: 226 Newly Diagnosed Multiple Myeloma (NDMM) patients in our center were included, the patients’ characteristics, survival, response, subgroup analysis, adverse reactions were compared between the patients with or without maintenance, proteasome inhibitor (PI) or immunomodulators (IMiDs) maintenance. And the survival of different maintenance duration of bortezomib-based regimens was also analyzed.Results: The maintenance therapy not only upgraded more patients’ response (34.3 vs. 13.3%, p= 0.006), but also significantly prolonged the patients’ PFS (median PFS: 41.1 vs. 10.5 months, p < 0.001) and OS (median OS: not reached vs. 38.6 months, p < 0.001). Compared with IMiDs, the PFS (median PFS: 43.7 vs. 38.5 months, p = 0.034) and OS (median OS: not reached vs. 78.5 months, p = 0.041) can both benefit from bortezomib-based maintenance. The patients younger than 65 years old with bortezomib-based maintenance significantly prolonged the OS (p= 0.032). Patients achieving the only partial response (PR) after induction and consolidation therapy experienced a significantly longer PFS and OS with bortezomib-based maintenance compared to IMiDs (p= 0.007, 0.002). Besides, the high-risk patients (ISS 2-3, DS 2-3 and RISS 2-3) with bortezomib-based maintenance can benefit PFS (p= 0.002, 0.02, 0.06, respectively) and OS (p=0.059, 0.047, 0.044, respectively) compared with IMiDs. The OS was significantly prolonged in the patients who received ≥12 months of bortezomib-based maintenance than those with maintenance < 12 months (p< 0.001), but no difference was observed in OS between the patients who received the 12-24 or ≥ 24months of bortezomib-based maintenance (p= 0.292).Conclusion: Maintenance therapy can significantly improve the survival of NDMM patients. Bortezomib-based regimens maintenance was more superior to IMiDs in overall PFS and OS. The beneficial effect is most evident in patients achieving the only PR after induction and consolidation therapy, and the high-risk patients. Moreover, younger patients also could benefit from bortezomib-based maintenance in OS. The bortezomib-based maintenance duration lasting 12-24 months after induction and consolidation therapy can reach a satisfactory OS.

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“…Three drug regimens utilising bortezomib, dexamethasone and an additional agent, such as cyclophosphamide (VCd), thalidomide (VTd) or lenalidomide (RVd), are the standard of care prior to autologous stem cell transplantation (ASCT), which utilises a melphalan-based conditioning regimen [ 23 ]. Following ASCT, bortezomib- or lenalidomide-based maintenance therapy is commenced to prolong response, slow progression and improve overall survival [ 24 , 25 , 26 ]. Patients ineligible for an ASCT are still evaluated for induction with bortezomib, lenalidomide or an alkylating-agent based regimen.…”

Section: Standard-of-care Therapy For Multiple Myelomamentioning

confidence: 99%

Targeted Therapies for Multiple Myeloma

Leow

Löw

2021

JPM

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Multiple myeloma continues to be a challenging disorder to treat despite improved therapies and the widespread use of proteasome inhibitors and immunomodulatory drugs. Although patient outcomes have improved, the disease continues to invariably relapse, and in the majority of cases, a cure remains elusive. In the last decade, there has been an explosion of novel drugs targeting cellular proteins essential for malignant plasma cell proliferation and survival. In this review, we focus on novel druggable targets leading to the development of monoclonal antibodies and cellular therapies against surface antigens (CD38, CD47, CD138, BCMA, SLAMF7, GPRC5D, FcRH5), inhibitors of epigenetic regulators such as histone deacetylase (HDAC), and agents targeting anti-apoptotic (BCL-2), ribosomal (eEF1A2) and nuclear export (XPO1) proteins.

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Bortezomib-based consolidation or maintenance therapy for multiple myeloma: a meta-analysis

Cited by 26 publications

References 35 publications

Different Patient Subgroup Different Maintenance, Proteasome Inhibitors or Immunomodulators Maintenance for Newly Diagnosed Multiple Myeloma: A 7-Year Single-Center Data in China

Different Patient Subgroup Different Maintenance, Proteasome Inhibitors or Immunomodulators Maintenance for Newly Diagnosed Multiple Myeloma: A 7-Year Single-Center Data in China

Proteasome Inhibitor or Immunomodulators Which is The Optimal Maintenance For Newly Diagnosed Multiple Myeloma: A 7-Year Real-World Data in China.

Targeted Therapies for Multiple Myeloma

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