Lenalidomide is thought to alter the
microenvironment in ways that favor activation of the immune system
against the disease.
The immune system is complex
involving many types of special cells such as macrophages, dendritic
cells, NK cells, T cells and B cells), and humoral components
The immune system can prevent development of cancers by eliminating
or suppressing oncogenic (cancer-driving) viral infections, altering
the inflammatory factors that may support tumor growth, and by
immune surveillance: identifying and destroying abnormal cells
before they can cause harm.
Studies have shown that lenalidomide
appears to work in different ways in different blood cell cancers.
These mechanism involved direct cytotoxicity (killing of tumor cells
without help from the immune system) as well as through indirect
effects on tumor immunity -- helping the immune system to "see" or
act on the tumor by changing the profile of host immune defenses.
How effective this drug can be may
depend on the individual's immune status and the biology of the
disease, which can vary by the type of lymphoma. Because its an oral
drug with immune-modulating properties there is interest in testing
lenalidomide with other immune-mediated drugs, such as Rituxan.
Lenalidomide has been shown to alter
different parts of the immune system by changing cytokine
production, regulating T cell co stimulation and augmenting the
Natural Killer cell cytotoxicity.
The immune modulating properties of Lenalidomide are thought to
account for its clinical efficacy in multiple myeloma, CLL and
myelodysplastic syndromes; where the disease distorts the immune
system by altering cytokine profiles in the tumor microenvironment.
Adapted from J Hematol Oncol. 2009
* Brit J Haematol 2014:
Lenalidomide plus rituximab can produce durable clinical
responses in patients with relapsed or refractory, indolent
Comment: Encouraging to see
good response rates in persons with Rituxan refractory
lymphoma (n=13 at 61%) and a 44% CR rate overall.
Limitations being the small study size (n =27) and no
control group. One issue is that the protocol involves being
on treatment for a long time (daily, indefinitely until
toxicity or progression) and the impact that might have on
quality of life … and also how to interpret duration of
response when to achieve it requires continuous therapy.
Business Wire 2013:
Studies Evaluating REVLIMID® (Lenalidomide) in Lymphoma
Presented at ASH
Immune-mediated actions of
J Hematol Oncol. 2009; Mechanism of action of lenalidomide in hematological malignancies
J Hematol Oncol. 2013
Immunomodulation therapy with lenalidomide in follicular,
transformed and diffuse large B cell lymphoma: current data
on safety and efficacy
initial promising data from these small trials, a larger
international phase II, single-arm, open-label study of
lenalidomide in 217 patients with biopsy-proven relapsed or
refractory aggressive DLBCL, FLG3, TmL, or MCL was initiated
In the NHL-003 trial, 217 patients had received a median of
3 (range, 1–13) prior treatment regimens .
The ORR was 35%; the PR rate was 22% and the CR/CRu rate was
13%. The median PFS was 3.7 months, and the median follow-up
period was 9.2 months. The most common grade 3 or 4 adverse
events were neutropenia (41.0%), thrombocytopenia (19.0%),
and anemia (9.2%).
In the NHL-003 trial, eight of the 19 patients with FLG3
(42%) achieved a response, two (11%) of whom achieved CR;
the median PFS duration in this trial was 8.9 months.9
Br J Haematol. 2013
Lenalidomide efficacy in activated B-cell-like subtype
diffuse large B-cell lymphoma is dependent upon IRF4 and
PubMed TOPIC Search: Rituxan
Mechanism of action of
lenalidomide in hematological malignancies