Lenalidomide in multiple myeloma: an evidence-based review of its role in therapy

Abstract

Introduction: Multiple myeloma (MM) is a relatively common and incurable hematological malignancy. Currently, there is no single standard therapy, with choice of treatment dependent on individual patient factors. Lenalidomide is an immunomodulatory drug with potent antitumor, antiangiogenic, immunomodulatory, and proapoptotic activity in MM. Aims: To evaluate the evidence for the use of lenalidomide in its current indication in relapsed or refractory MM, and additionally its investigational use for the treatment of newly diagnosed MM. Evidence review: In patients with relapsed and refractory MM, adding lenalidomide to high-dose dexamethasone significantly improves response rates and time-to-progression, relative to high-dose dexamethasone alone. This translates into a significant extension of overall survival (with a median extension of 9.1 months in a pivotal phase III study). Outcome is independent of patient age, number of previous therapies, type of previous therapy (including thalidomide or autologous stem cell transplantation), renal impairment, and β 2 -microglobulin level. Evidence suggests that combining lenalidomide with low-dose dexamethasone improves outcomes in patients with newly diagnosed disease and is superior to lenalidomide combined with highdose dexamethasone. Myelosuppression is the predominant toxicity observed, although some studies have shown high incidences of venous thromboembolism in the absence of prophylactic antithrombotic anticoagulation therapy. There is currently only limited evidence regarding the health economics of lenalidomide. Role in therapy:The encouraging results obtained with lenalidomide alone and in combination with dexamethasone in patients with relapsed or refractory MM have led to its adoption as a recommended therapy in patients who have received at least one prior treatment. Emerging evidence supports the ongoing investigation of lenalidomide in combination with low-dose dexamethasone, and in other combinations including bortezomib, for use both in relapsed, refractory, and newly diagnosed MM.

In vitro effects of perifosine, bortezomib and lenalidomide against hematopoietic progenitor cells from healthy donors

“…In line with our observations, a previous study found that perifosine (2 μM) tended to reduce the clonogenic activity of normal CD34 + cells [31]. The immunomodulatory substance lenalidomide is highly effective in the treatment of multiple myeloma and MDS, but an important side effect is hematotoxicity [13,[20][21][22][23]. If combined with dexamethasone as initial multiple myeloma therapy, it increases thrombocytopenia and neutropenia significantly, but anemia only slightly, in comparison to dexamethasone alone [32].…”

“…The immunomodulatory substance lenalidomide showed promising results in the treatment of different hematological malignancies such as multiple myeloma, myelodysplastic syndrome (MDS) and chronic lymphocytic leukemia (CLL) [13][14][15]. Immunomodulation, antiangiogenic effects and direct induction of cytotoxicity may contribute to the clinically documented efficacy of this agent [15][16][17][18][19][20].…”

CPS49‐induced neurotoxicity does not cause limb patterning anomalies in developing chicken embryos

“…This has begun to be addressed recently through studying the pharmacological properties of analogs or breakdown products of the drug experimentally and clinically (Richardson et al. ; Mahony et al. ; Beedie et al.…”

“…Further understanding of the molecular and morphological action of this drug will aid in uncovering newer, safer alternatives. This has begun to be addressed recently through studying the pharmacological properties of analogs or breakdown products of the drug experimentally and clinically (Richardson et al 2010;Mahony et al 2013;Beedie et al 2015Beedie et al , 2016. Our previous studies of an anti-angiogenic thalidomide analog, CPS49, demonstrated the drug leads to widespread loss of blood vessels throughout the limb, when applied at the time of rapid limb growth [Hamburger and Hamilton (HH) St 17-19 in the chicken embryo], and disrupts the actin cytoskeleton of endothelial cells in vitro (Therapontos et al 2009).…”

Lenalidomide in Multiple Myeloma—A Practice Guideline

“…After full text screening, fifty-two publications were included: two practice guidelines 4,5 ; three systematic reviews [6][7][8] ; ten unique primary studies, of which five were full-text publications 1,2,9-11 and five were conference abstracts [12][13][14][15][16] . Forty-two publications were ancillary to the ten unique primary studies, including secondary analyses or follow-up data from the main publications (Table i).…”