Immunomodulating agents
Immunomodulating agents are a new class of drugs that
change the expression of various cytokines and costimulate
immune effector cells. Lenalidomide (Revlimid, Celgene) is
a second generation thalidomide analog with possible immu-
nomodulating and antiangiogenic properties, which may also
modulate cytokine activity in the tumor microenvironment.
Lenalidomide is orally available and has significant activity in
multiple myeloma and myelodysplastic syndrome, and most
recently it has been shown to be effective in the treatment of
various lymphoproliferative disorders such as CLL and NHL
[54]. A characteristic AE of treatment with lenalidomide in
CLL is tumor
flare reaction, as well as an immune-modulatory
effect which leads to a sensation of heat and burning in the
lymph nodes. Chanan-Khan et al. investigated the antileuke-
mic effects of lenalidomide in 45 CLL patients with relapsed
or refractory disease [55]. The drug was administered orally at
a dose of 25 mg once a day for 21 days on a 28-day schedule.
Due to the occurrence of tumor lysis syndrome (TLS) in two
of the
first 29 patients, the treatment protocol was revised to
allow slow dose escalation in subsequent patients, in whom
the initial dose was 5 mg, which was increased by 5 mg every
1–2 weeks to a maximum 25 mg. Twenty-nine patients were
assessable for response and all 45 patients were evaluated for
toxicity. The most common nonhematologic AEs were fatigue
(83%) and
flare reaction (58%). Grade 3–4 thrombocytopenia
a c t a h a e m a t o l o g i c a p o l o n i c a 4 5 ( 2 0 1 4 ) 1 2 2 – 1 3 1 127
was noted in 45% of the patients and grade 3–4 neutropenia
in 70% of the patients. Major responses were observed in 21
patients (41%) with 4 CRs (9%) and 17 (38%) achieving a PR in
intent-to-treat analysis. The median PFS time has not been
reached.
Ferrajoli et al. report the results of a phase II study in
which lenalidomide was administered at 10 mg per day by
continuous daily dosing with dose escalation up to 25 mg,
based on patient tolerability and response [56]. Patients who
had stable disease continued treatment until disease progression.
Forty-four patients with relapsed or refractory CLL
were included. Three patients (7%) achieved a CR, one
nodular PR and 10 patients a PR, at an OR rate of 32%. The
treatment was effective in 31% of the patients with high risk
cytogenetic abnormalities (del11q or del 17p), 24% of the
patients with un-mutated VH and 25% of the patients
refractory to
fludarabine. Thirteen patients (30%) developed
tumor
flare reaction. Despite a median dose of 10 mg daily,
significant hematologic toxicity was frequently observed.
Grade 3–4 neutropenia was noted in 41% of the courses and
grade 3–4 thrombocytopenia in 16% of the patients.
Subsequently, Andritsos et al. reported four consecutive
patients with CLL who were treated with lenalidomide and all
had serious adverse events [57]. The drug was administered
at a dose of 25 mg/day for 21 days of a 28-day cycle. Tumor
flare was observed in three patients and was characterized by
painful lymph node enlargement, with one fatal outcome.
Another patient developed sepsis and renal failure. The
efficacy of lenalidomide may be increased with the addition
of rituximab. Badoux et al. reported an OR rate of 66%
(including 12% CR) and an estimated 36-month survival of
71% in relapsed or refractory CLL patients treated with this
combination [58]. In another phase II clinical trial treatment
with lenalidomide and rituximab as the
first-line therapy
induced OR in more than 90% of the patients, including an
OR rate of 53% (CR 13%) in patients with (17p) deletion [59].
The ORIGIN trial compares the safety and efficacy of
lenalidomide with those of chlorambucil in patients with
CLL, 65 years and older (NCT00910910). Interim analysis
showed higher rates of death in patients treated with
lenalidomide compared to those treated with chlorambucil,
and the recruitment for the study was stopped. Currently,
lenalidomide is under evaluation for maintenance in phase
III study in patients with CLL following
first-line therapy
(CLLM1) (NCT01556776).
Immunomodulating agents
Immunomodulating agents are a new class of drugs that
change the expression of various cytokines and costimulate
immune effector cells. Lenalidomide (Revlimid, Celgene) is
a second generation thalidomide analog with possible immu-
nomodulating and antiangiogenic properties, which may also
modulate cytokine activity in the tumor microenvironment.
Lenalidomide is orally available and has significant activity in
multiple myeloma and myelodysplastic syndrome, and most
recently it has been shown to be effective in the treatment of
various lymphoproliferative disorders such as CLL and NHL
[54]. A characteristic AE of treatment with lenalidomide in
CLL is tumor
flare reaction, as well as an immune-modulatory
effect which leads to a sensation of heat and burning in the
lymph nodes. Chanan-Khan et al. investigated the antileuke-
mic effects of lenalidomide in 45 CLL patients with relapsed
or refractory disease [55]. The drug was administered orally at
a dose of 25 mg once a day for 21 days on a 28-day schedule.
Due to the occurrence of tumor lysis syndrome (TLS) in two
of the
first 29 patients, the treatment protocol was revised to
allow slow dose escalation in subsequent patients, in whom
the initial dose was 5 mg, which was increased by 5 mg every
1–2 weeks to a maximum 25 mg. Twenty-nine patients were
assessable for response and all 45 patients were evaluated for
toxicity. The most common nonhematologic AEs were fatigue
(83%) and
flare reaction (58%). Grade 3–4 thrombocytopenia
a c t a h a e m a t o l o g i c a p o l o n i c a 4 5 ( 2 0 1 4 ) 1 2 2 – 1 3 1 127
was noted in 45% of the patients and grade 3–4 neutropenia
in 70% of the patients. Major responses were observed in 21
patients (41%) with 4 CRs (9%) and 17 (38%) achieving a PR in
intent-to-treat analysis. The median PFS time has not been
reached.
Ferrajoli et al. report the results of a phase II study in
which lenalidomide was administered at 10 mg per day by
continuous daily dosing with dose escalation up to 25 mg,
based on patient tolerability and response [56]. Patients who
had stable disease continued treatment until disease progression.
Forty-four patients with relapsed or refractory CLL
were included. Three patients (7%) achieved a CR, one
nodular PR and 10 patients a PR, at an OR rate of 32%. The
treatment was effective in 31% of the patients with high risk
cytogenetic abnormalities (del11q or del 17p), 24% of the
patients with un-mutated VH and 25% of the patients
refractory to
fludarabine. Thirteen patients (30%) developed
tumor
flare reaction. Despite a median dose of 10 mg daily,
significant hematologic toxicity was frequently observed.
Grade 3–4 neutropenia was noted in 41% of the courses and
grade 3–4 thrombocytopenia in 16% of the patients.
Subsequently, Andritsos et al. reported four consecutive
patients with CLL who were treated with lenalidomide and all
had serious adverse events [57]. The drug was administered
at a dose of 25 mg/day for 21 days of a 28-day cycle. Tumor
flare was observed in three patients and was characterized by
painful lymph node enlargement, with one fatal outcome.
Another patient developed sepsis and renal failure. The
efficacy of lenalidomide may be increased with the addition
of rituximab. Badoux et al. reported an OR rate of 66%
(including 12% CR) and an estimated 36-month survival of
71% in relapsed or refractory CLL patients treated with this
combination [58]. In another phase II clinical trial treatment
with lenalidomide and rituximab as the
first-line therapy
induced OR in more than 90% of the patients, including an
OR rate of 53% (CR 13%) in patients with (17p) deletion [59].
The ORIGIN trial compares the safety and efficacy of
lenalidomide with those of chlorambucil in patients with
CLL, 65 years and older (NCT00910910). Interim analysis
showed higher rates of death in patients treated with
lenalidomide compared to those treated with chlorambucil,
and the recruitment for the study was stopped. Currently,
lenalidomide is under evaluation for maintenance in phase
III study in patients with CLL following
first-line therapy
(CLLM1) (NCT01556776).
การแปล กรุณารอสักครู่..
Immunomodulating agents
Immunomodulating agents are a new class of drugs that
change the expression of various cytokines and costimulate
immune effector cells. Lenalidomide (Revlimid, Celgene) is
a second generation thalidomide analog with possible immu-
nomodulating and antiangiogenic properties, which may also
modulate cytokine activity in the tumor microenvironment.
Lenalidomide is orally available and has significant activity in
multiple myeloma and myelodysplastic syndrome, and most
recently it has been shown to be effective in the treatment of
various lymphoproliferative disorders such as CLL and NHL
[54]. A characteristic AE of treatment with lenalidomide in
CLL is tumor
flare reaction, as well as an immune-modulatory
effect which leads to a sensation of heat and burning in the
lymph nodes. Chanan-Khan et al. investigated the antileuke-
mic effects of lenalidomide in 45 CLL patients with relapsed
or refractory disease [55]. The drug was administered orally at
a dose of 25 mg once a day for 21 days on a 28-day schedule.
Due to the occurrence of tumor lysis syndrome (TLS) in two
of the
first 29 patients, the treatment protocol was revised to
allow slow dose escalation in subsequent patients, in whom
the initial dose was 5 mg, which was increased by 5 mg every
1–2 weeks to a maximum 25 mg. Twenty-nine patients were
assessable for response and all 45 patients were evaluated for
toxicity. The most common nonhematologic AEs were fatigue
(83%) and
flare reaction (58%). Grade 3–4 thrombocytopenia
a c t a h a e m a t o l o g i c a p o l o n i c a 4 5 ( 2 0 1 4 ) 1 2 2 – 1 3 1 127
was noted in 45% of the patients and grade 3–4 neutropenia
in 70% of the patients. Major responses were observed in 21
patients (41%) with 4 CRs (9%) and 17 (38%) achieving a PR in
intent-to-treat analysis. The median PFS time has not been
reached.
Ferrajoli et al. report the results of a phase II study in
which lenalidomide was administered at 10 mg per day by
continuous daily dosing with dose escalation up to 25 mg,
based on patient tolerability and response [56]. Patients who
had stable disease continued treatment until disease progression.
Forty-four patients with relapsed or refractory CLL
were included. Three patients (7%) achieved a CR, one
nodular PR and 10 patients a PR, at an OR rate of 32%. The
treatment was effective in 31% of the patients with high risk
cytogenetic abnormalities (del11q or del 17p), 24% of the
patients with un-mutated VH and 25% of the patients
refractory to
fludarabine. Thirteen patients (30%) developed
tumor
flare reaction. Despite a median dose of 10 mg daily,
significant hematologic toxicity was frequently observed.
Grade 3–4 neutropenia was noted in 41% of the courses and
grade 3–4 thrombocytopenia in 16% of the patients.
Subsequently, Andritsos et al. reported four consecutive
patients with CLL who were treated with lenalidomide and all
had serious adverse events [57]. The drug was administered
at a dose of 25 mg/day for 21 days of a 28-day cycle. Tumor
flare was observed in three patients and was characterized by
painful lymph node enlargement, with one fatal outcome.
Another patient developed sepsis and renal failure. The
efficacy of lenalidomide may be increased with the addition
of rituximab. Badoux et al. reported an OR rate of 66%
(including 12% CR) and an estimated 36-month survival of
71% in relapsed or refractory CLL patients treated with this
combination [58]. In another phase II clinical trial treatment
with lenalidomide and rituximab as the
first-line therapy
induced OR in more than 90% of the patients, including an
OR rate of 53% (CR 13%) in patients with (17p) deletion [59].
The ORIGIN trial compares the safety and efficacy of
lenalidomide with those of chlorambucil in patients with
CLL, 65 years and older (NCT00910910). Interim analysis
showed higher rates of death in patients treated with
lenalidomide compared to those treated with chlorambucil,
and the recruitment for the study was stopped. Currently,
lenalidomide is under evaluation for maintenance in phase
III study in patients with CLL following
first-line therapy
(CLLM1) (NCT01556776).
การแปล กรุณารอสักครู่..