Gupta et al Journal of Drug Delivery & Therapeutics; 2014, 4(3), 87-90 87
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MINI REVIEW
LENALIDOMIDE: RECENT ARMAMENTARIUM IN MANAGEMENT OF MULTIPLE
MYELOMA
*Dr Gupta Ajay K, Dr Sharma Ashok K, Dr Khadka Anjan, Dr Sharma Sushil, Dr Dahiya Navdeep, Dr Brashier DB
Armed Forces Medical College (AFMC), Department of Pharmacology, Pune-40, India
*Corresponding author: Dr AK Gupta, Associate Professor, Department of Pharmacology, AFMC, Wanworie, Pune-
40, Postal code- 411040 ajayneera2007@rediffmail.com +919765090428
INTRODUCTION
Lenalidomide is a novel oral immunomodulatory
derivative of thalidomide with potent activity and with a
much improved toxicity profile to the parent compound.
Thalidomide has a potential to treat inflammatory and
neoplastic condition like multiple myeloma but was
withdrawn from the market after its teratogenic effects
were established.
1
Lenalidomide, a potent analogue of
thalidomide was developed with improvement in safety
and efficacy than the parent drug, thalidomide.It was
created using thalidomide as a template by adding an
amino group to the 4th carbon of the phthaloyl ring and
removal of a carbonyl group.
Lenalidomide possesses immunomodulatory, anti-
angiogenic, antineoplastic and anti-inflammatory
activities. Lenalidomide has been extensively studied and
approved for refractory / relapsing multiple myeloma
(MM), mantle cell lymphoma (MCL) and
myelodysplastic syndromes (MDS).
2
Multiple myeloma is a B cell malignancy characterized
by accumulation of plasma cell clone in the bone
marrow, monoclonal protein in serum and/or urine,
reduced immunoglobulin levels and lytic bone
disease.
3
Alkylating agents, anthracyclines and
corticosteroids were commonly used drugs in multiple
myeloma which extended patient’s survival to median 3-
4 yearsas compared to median survival of 4-5 years with
high dose of these drugs followed by autologous
transplantation.
4
Due to the development of tumor cell
resistance to all therapies, multiple myeloma still
remains incurable, requiring further study on novel
treatment strategies.
5
The survival in MM patients has
improved significantly in the past decade due to the
introduction of novel agents including
immunomodulatory drugs
(thalidomide, lenalidomide and pomalidomide),
proteasome inhibitors (bortezomib, carfilzomib,
marizomib and ixazomib citrate), monoclonal antibodies
(elotuzumab, siltuximab, daratumumab and BT-062),
and drugs affecting an interaction with the tumor
microenvironment (anti-VLA4 monoclonal antibody,
chemokine CXCR4 inhibitor AMD-3100 and selectin
inhibitor GMI-1070).
6-8
Lenalidomide has been found to be more potent in the
stimulation of T-cell proliferation and INF gamma and
IL-2 production than thalidomide, whereas both
thalidomide and pomalidomide, another thalidomide
analogue, have been found to be more potent at
inhibiting sprout formation than lenalidomide when
antiangiogenic properties were assessed in a human
umbilical explant model. Thalidomide was associated
with dose-limiting toxicities including somnolence,
constipation, neuropathy, and increased incidence of
venothromboembolism (VTE), especially when
combined with dexamethasone
9
.No clinical trials directly
comparing these agents have been performed,
lenalidomide appears to have a lower incidence of
constipation, peripheral neuropathy, and somnolence
than thalidomide.
2
Structure
(RS)-3-(4-Amino-1-oxo 1,3-dihydro-2H-isoindol- 2-
yl)piperidine-2,6-dione
ABSTRACT
Lenalidomide is an analogue of thalidomide. It is an oral immunomodulatory compound with potent activity and different
toxicity profile than thalidomide. Lenalidomide is one of the novel drug agents used to treat multiple myeloma. Multiple
myeloma (MM) is a B cell malignancy characterized by excess monotypic plasma cells in the bone marrow. Lenalidomide in
combination with dexamethasone is one of the most promising MM novel treatment options. It induces at least additive direct
cytotoxicity in multiple myeloma cells.The lenalidomide has possibility of being used as an adjuvant in support of more
specific immunotherapeutic interventions including cancer chemotherapy, anticancer vaccines and adoptively transferred cells
which warrants further investigation.
Key words: Dexamethasone, Immunomodulation, Lenalidomide, Multiple myeloma