5 research outputs found
Does low-molecular-weight heparin influence the antimyeloma effects of thalidomide? A retrospective analysis of data from the GIMEMA, nordic and turkish myeloma study groups
Background/Aim: Low-molecular-weight heparin (LMWH) has been shown to prolong survival among patients with solid tumors, but its role among myeloma patients is unknown. Patients: Data from the GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto), Nordic and Turkish myeloma study groups comparing melphalan and prednisolone with (MPT, n: 404) or without thalidomide (MP, n: 393) are analyzed for effects of LMWH. Forty percent (159/394) of the patients on MPT and 7.4% (29/390) in the MP arm received LMWH. Results: Thalidomide improved response and progression-free survival (PFS). Regardless of thalidomide treatment, response rate was higher among those receiving LMWH vs. none vs. other anticoagulants (58.1 vs. 44.9 vs. 50.4%, p = 0.01). PFS was significantly longer (median 32 vs. 21 and 17 vs. 17 months, p = 0.004) only among international scoring system (ISS) I patients receiving MPT +/- LMWH vs. MP +/- LMWH. The group of MPT patients who also received LMWH had a better OS compared to those who did not [45 months, 95% confidence interval (CI) 27.7-62.3, vs. 32 months, 95% CI 26.1-37.9; p = 0.034]. When multivariate analysis was repeated in subgroups, thalidomide was no longer a significant factor (response, PFS) among those receiving LMWH. Conclusion: Addition of LMWH to MPT, in particular in patients with low ISS, suggests additive effects, but the results are limited by the retrospective design of our study. (C) 2015 S. Karger AG, Base
Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data
Background Lenalidomide has been linked to second primary malignancies
in myeloma. We aimed to pool and analyse available data to compare the
incidence of second primary malignancies in patients with and without
lenalidomide exposure.
Methods We identified relevant studies through a search of PubMed and
abstracts from the American Society of Clinical Oncology, American
Society of Hematology, and the International Myeloma Workshop.
Randomised, controlled, phase 3 trials that recruited patients with
newly diagnosed multiple myeloma between Jan 1, 2000, and Dec 15, 2012,
and in which at least one group received lenalidomide were eligible for
inclusion. We obtained individual patient data (age, sex, date of
diagnosis, allocated treatment and received treatment, duration of
treatment and cause of discontinuation, maintenance treatment, date of
first relapse, date of second primary malignancy diagnosis, type of
second primary malignancy, date of death or last contact, and cause of
death) by direct collaboration with the principal investigators of
eligible trials. Primary outcomes of interest were cumulative incidence
of all second primary malignancies, solid second primary malignancies,
and haematological second primary malignancies, and were analysed by a
one-step meta-analysis.
Findings We found nine eligible trials, of which seven had available
data for 3254 patients. 3218 of these patients received treatment (2620
had received lenalidomide and 598 had not), and were included in our
analyses. Cumulative incidences of all second primary malignancies at 5
years were 6.9% (95% CI 5.3-8.5) in patients who received lenalidomide
and 4.8% (2.0-7.6) in those who did not (hazard ratio [HR] 1.55
[95% CI 1.03-2.34]; p=0.037). Cumulative 5-year incidences of solid
second primary malignancies were 3.8% (95% CI 2.7-4.9) in patients who
received lenalidomide and 3.4% (1.6-5.2) in those that did not (HR 1.1
[95% CI 0.62-2.00]; p=0.72), and of haematological second primary
malignancies were 3.1% (95% CI 1.9-4.3) and 1.4% (0.0-3.6),
respectively (HR 3.8 [95% CI 1.15-12.62]; p=0.029). Exposure to
lenalidomide plus oral melphalan significantly increased haematological
second primary malignancy risk versus melphalan alone (HR 4.86 [95%
CI 2.79-8.46]; p<0.0001). Exposure to lenalidomide plus cyclophosphamide
(HR 1.26 [95% CI 0.30-5.38]; p=0.75) or lenalidomide plus
dexamethasone (HR 0.86 [95% CI 0.33-2.24]; p=0.76) did not increase
haematological second primary malignancy risk versus melphalan alone.
Interpretation Patients with newly diagnosed myeloma who received
lenalidomide had an increased risk of developing haematological second
primary malignancies, driven mainly by treatment strategies that
included a combination of lenalidomide and oral melphalan. These results
suggest that alternatives, such as cyclophosphamide or alkylating-free
combinations, should be considered instead of oral melphalan in
combination with lenalidomide for myeloma