Lenalidomide in combination with bendamustine and prednisolone in relapsed/refractory multiple myeloma: results of a phase 2 clinical trial (OSHO-#077)

Beck, Juliane; Schwarzer, Andreas; Gläser, Dietrich; Mügge, Lars-Olof; Uhlig, Jens; Heyn, Simone; Kragl, Brigitte; Mohren, Martin; Hoffmann, Franz Albert; Lange, Thoralf; Schliwa, Thomas; Zehrfeld, Thomas; Becker, Cornelia; Kreibich, Ute; Winkelmann, Cornelia; Edelmann, Thomas; Andrea, Marc; Bill, Marius; Jentzsch, Madlen; Schwind, Sebastian; Niederwieser, Dietger; Pönisch, Wolfram

doi:10.1007/s00432-017-2504-5

Cited by 12 publications

(9 citation statements)

References 25 publications

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“…This forest plot illustrates the percentage of events per 100 patient‐cycles for respective therapies. BPR indicates bendamustine, prednisone, and lenalidomide; CPR, cyclophosphamide, prednisone, and lenalidomide; HDACi, histone deacetylase inhibitor; MoAB, monoclonal antibody; MPR, melphalan, prednisone, and lenalidomide; mTORi, mammalian target of rapamycin inhibitor; PI, proteasome inhibitor; R, lenalidomide; Rd, lenalidomide and low‐dose dexamethasone …”

Section: Resultsmentioning

confidence: 99%

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Venous thromboembolism risk with contemporary lenalidomide‐based regimens despite thromboprophylaxis in multiple myeloma: A systematic review and meta‐analysis

Chakraborty

Riaz

Malik

et al. 2020

Cancer

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Background Thromboprophylaxis is routinely used with lenalidomide‐based regimens in multiple myeloma because of a substantial risk of venous thromboembolism (VTE). However, little is known about the incidence of VTE with contemporary lenalidomide‐based regimens. The objective of the current study was to estimate the incidence of VTE despite thromboprophylaxis with currently used lenalidomide‐based regimens in patients with myeloma. Methods The Ovid MEDLINE, Embase, and Cochrane databases were queried from study inception to January 2019 for keywords to cover the following concepts: “lenalidomide,” “venous thromboembolism,” and “multiple myeloma.” Phase 1, 2, and 3 clinical trials evaluating lenalidomide‐based regimens with thromboprophylaxis were included. The pooled incidence rate of VTE was estimated using a random‐effects model. Results The search generated 1372 citations, with 51 clinical trials and 9069 patients included for analysis. The most common thromboprophylaxis agents were aspirin, low‐molecular‐weight heparin or warfarin, administered either per risk‐stratification or at investigators' discretion. The pooled incidence of VTE in trials of patients who had newly diagnosed and relapsed/refractory myeloma was 6.2% (95% CI, 5.4%‐7.1%) over median treatment durations ranging from 2 to 34 cycles, which translated into 1.2 VTE events per 100 patient‐cycles (95% CI, 0.9‐1.7 VTE events per 100 patient‐cycles). Among contemporary regimens, the risk of VTE was low with combined lenalidomide and low‐dose dexamethasone (0.2 [95% CI, 0.1‐0.6] events/100 patient‐cycles) and lenalidomide maintenance (0.0 [95% CI, 0.0‐0.7] events per 100 patient‐cycles). VTE risk was higher with combined lenalidomide and low‐dose dexamethasone plus proteasome inhibitors (1.3 [95% CI, 0.7‐2.3] events per 100 patient‐cycles). Conclusions Despite adequate thromboprophylaxis, lenalidomide‐based regimens have a substantial risk of VTE in controlled clinical trial settings. Further studies are needed on new thromboprophylaxis strategies with regimens that have a high VTE risk.

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Section: Resultsmentioning

confidence: 99%

“…In total, 245 duplicate records were removed, and 1127 records were screened. Ultimately, 51 clinical trials with 61 Len‐containing treatment arms and 9069 patients were included for the analysis based on a priori selection criteria (Fig. ) …”

Section: Resultsmentioning

confidence: 99%

Venous thromboembolism risk with contemporary lenalidomide‐based regimens despite thromboprophylaxis in multiple myeloma: A systematic review and meta‐analysis

Chakraborty

Riaz

Malik

et al. 2020

Cancer

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“…Previous studies mainly used bendamustine in combination with other drugs (glucocorticoids, PIs, or IMiDs) as an alternative for patients with RRMM [ 128 ]. The triplet of bendamustine, ixazomib, and DEX (BID) was used in a phase I/II trial in patients with RRMM who previously had received a median of 4 (range 4–9) lines of therapy.…”

Section: Alkylating Agentsmentioning

confidence: 99%

Emerging agents and regimens for multiple myeloma

Yang

et al. 2020

J Hematol Oncol

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The outcomes of multiple myeloma (MM) have been improved significantly with the therapies incorporating proteasome inhibitors (PI), immunomodulatory drugs, monoclonal antibodies (MoAb) and stem cell transplantation. However, relapsed and refractory MM (RRMM) remains a major challenge. Novel agents and regimens are under active clinical development. These include new PIs such as ixazomib, marizomib, and oprozomib; new MoAbs such as isatuximab and MOR202; novel epigenetic agent ricolinostat and novel cytokines such as siltuximab. Recently, the first XPO-1 inhibitor, selinexor, was approved for RRMM. BCMA-targeted BiTE, antibody–drug conjugates and CAR-T cells have the potential to revolutionize the therapy for RRMM. In this review, we summarized the latest clinical development of these novel agents and regimens.

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“…However, they achieved a higher degree of both metastasis and tumor growth inhibition when dihydroartemisinin and cyclophosphamide were used in combination [ 54 ]. Liu and colleagues found that a combination of artesunate with lenalinomide, commonly used for the treatment of Multiple Myeloma [ 55 ], produced an impressive enhancement of antineoplastic activity in polyploid cell lines [ 56 ]. Tilaoui and colleagues also observed a synergistic effect when they used vincristine and artemisinin in combination against murin mastocytoma (P815) cells [ 37 ].…”

Section: Artemisinin As a Treatment For Cancermentioning

confidence: 99%

Artemisinin and Its Synthetic Derivatives as a Possible Therapy for Cancer

et al. 2018

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To assess the possibility of using the antimalarial drug artemisinin and its synthetic derivatives as antineoplastic drugs. A Pubmed and Google Scholar (1983–2018) search was performed using the terms artemisinin, cancer, artesunate and Artemisia annua. Case reports and original research articles, review articles, and clinical trials in both humans and animals were evaluated. Both in vitro and in vivo clinical trials and case reports have shown promising activity of the artemisinin drug derivatives in treating certain types of cancer. However, the reported articles are few, and therefore not statistically significant. The minimal toxicity shown in clinical trials and case reports, along with the selective cytotoxic activity of the compounds, make them possible cancer therapies due to the emerging evidence of the drug’s effectiveness.

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Lenalidomide in combination with bendamustine and prednisolone in relapsed/refractory multiple myeloma: results of a phase 2 clinical trial (OSHO-#077)

Cited by 12 publications

References 25 publications

Venous thromboembolism risk with contemporary lenalidomide‐based regimens despite thromboprophylaxis in multiple myeloma: A systematic review and meta‐analysis

Venous thromboembolism risk with contemporary lenalidomide‐based regimens despite thromboprophylaxis in multiple myeloma: A systematic review and meta‐analysis

Emerging agents and regimens for multiple myeloma

Artemisinin and Its Synthetic Derivatives as a Possible Therapy for Cancer

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