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S L Corthals,
S M Sun,
R Kuiper,
Y de Knegt,
A Broyl,
B van der Holt,
H B Beverloo,
J K Peeters,
L el Jarari,
H M Lokhorst, S Zweegman,
M Jongen-Lavrencic,
P Sonneveld
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 06/2011; 25(11):1784-9. · 8.30 Impact Factor
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Silvia G R Verelst,
F Termorshuizen,
C A Uyl-de Groot,
M R Schaafsma,
A H M Ammerlaan,
S Wittebol,
H A M Sinnige, S Zweegman,
M van Marwijk Kooy,
R van der Griend,
H M Lokhorst,
P Sonneveld,
P W Wijermans
[show abstract]
[hide abstract]
ABSTRACT: Thalidomide with melphalan/prednisone (MPT) was defined as standard treatment in elderly patients with multiple myeloma (MM) based on five randomized trials. In one of these trials, HOVON49, a prospective health-related quality-of-life (HRQoL) study was initiated in order to assess the impact of thalidomide on QoL. Patients aged >65 years with newly diagnosed MM were randomized to receive melphalan plus prednisone (MP) or MPT, followed by thalidomide maintenance in the MPT arm. Two hundred eighty-four patients were included in this side study (MP, n=149; MPT n=135). HRQoL was assessed with the EORTC Core QoL Questionnaire (QLQ-C30) and the myeloma-specific module (QLQ-MY24) at baseline and at predetermined intervals during treatment. The QLQ-C30 subscales physical function (P=0.044) and constipation (P<0.001) showed an improvement during induction in favour of the MP arm. During thalidomide maintenance, the scores for the QLQ-MY24 paraesthesia became significantly higher in the MPT arm (P<0.001). The QLQ-C30 subscales pain (P=0.12), insomnia (P=0.068), appetite loss (P=0.074) and the QLQ-MY24 item sick (P=0.086) scored marginally better during thalidomide maintenance. The overall QoL-scale QLQ-C30-HRQoL showed a significant time trend towards more favourable mean values during protocol treatment without differences between MP and MPT. For the QLQ-C30 subscales emotional function and future perspectives, difference in favour of the MPT arm from the start of treatment was observed (P=0.018 and P=0.045, respectively) with no significant 'time × arm' interaction, indicating a persistent better patient perspective with MPT treatment. This study shows that the higher frequency of toxicity associated with MPT does not translate into a negative effect on HRQoL and that MPT holds a better patient perspective.
Annals of Hematology 04/2011; 90(12):1427-39. · 2.62 Impact Factor
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M A Dimopoulos,
A Palumbo,
M Attal,
M Beksaç,
F E Davies,
M Delforge,
H Einsele,
R Hajek,
J-L Harousseau,
F Leal da Costa,
H Ludwig,
U-H Mellqvist,
G J Morgan,
J F San-Miguel, S Zweegman,
P Sonneveld
[show abstract]
[hide abstract]
ABSTRACT: An expert panel convened to reach a consensus regarding the optimal use of lenalidomide in combination with dexamethasone (Len/Dex) in patients with relapsed or refractory multiple myeloma (RRMM). On the basis of the available evidence, the panel agreed that Len/Dex is a valid and effective treatment option for most patients with RRMM. As with other therapies, using Len/Dex at first relapse is more effective regarding response rate and durability than using it after multiple salvage therapies. Len/Dex may be beneficial regardless of patient age, disease stage and renal function, although the starting dose of lenalidomide should be adjusted for renal impairment and cytopenias. Long-term treatment until there is evidence of disease progression may be recommended at the best-tolerated doses of both lenalidomide and dexamethasone. Recommendations regarding the prevention and management of adverse events, particularly venous thromboembolism and myelosuppression, were provided on the basis of the available evidence and practical experience of panel members. Ongoing trials will provide more insight into the effects of continuous lenalidomide-based therapy in myeloma.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 02/2011; 25(5):749-60. · 8.30 Impact Factor
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[show abstract]
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ABSTRACT: For relapsed multiple myeloma (MM) patients, allo-SCT is a possible treatment option, but recent data obtained using a nonmyeloablative (NMA) conditioning regimen are scarce. We retrospectively collected data from 38 relapsed MM patients who received a NMA allo-SCT from October 2001 to January 2008. In total, 18 patients (48%) were transplanted using a matched unrelated donor. The median follow-up is 2.3 years. In 16 patients (42%) the response improved and eight patients (21%) were rapidly progressive within 6 months after allo-SCT. In total, 15 patients (39%) were in CR after allo-SCT. The median PFS was 1.4 years (range, 0.1-4.9), and having a CR after allo-SCT or having chronic GVHD resulted in longer PFS. Median OS was 3.1 years (range, 0.2-7.2) and again having a CR after allo-SCT or chronic GVHD was associated with a better OS. Six patients (16%) have died from treatment-related diseases. These results indicate that NMA allo-SCT is a treatment option in relapsed MM patients and that results may be improved by strategies that enhance the CR rate after allo-SCT.
Bone marrow transplantation 02/2011; 46(2):244-9. · 3.00 Impact Factor
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Henk M Lokhorst,
Bronno van der Holt, Sonja Zweegman,
Edo Vellenga,
Sandra Croockewit,
Marinus H van Oers,
Peter von dem Borne,
Pierre Wijermans,
Ron Schaafsma,
Okke de Weerdt, [......],
Michel Delforge,
Henriëtte Berenschot,
Gerard M Bos,
Kon-Siong G Jie,
Harm Sinnige,
Marinus van Marwijk-Kooy,
Peter Joosten,
Monique C Minnema,
Rianne van Ammerlaan,
Pieter Sonneveld
[show abstract]
[hide abstract]
ABSTRACT: The phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and dexamethasone, or to arm B: thalidomide 200 mg orally, days 1 to 28 plus adriamycin and dexamethasone. After induction therapy and stem cell mobilization, patients were to receive high-dose melphalan, 200 mg/m(2), followed by maintenance with alpha-interferon (arm A) or thalidomide 50 mg daily (arm B). Thalidomide significantly improved overall response rate as well as quality of the response before and after high dose melphalan. Best overall response rate on protocol was 88% and 79% (P = .005), at least very good partial remission 66% and 54% (P = .005), and complete remission 31% and 23% (P = .04), respectively, in favor of the thalidomide arm. Thalidomide also significantly improved event-free survival from median 22 months to 34 months (P < .001), and prolonged progression free from median 25 months to 34 months (P < .001). Median survival was longer in the thalidomide arm, 73 versus 60 months; however, this difference was not significant (P = .77). Patients randomized to thalidomide had strongly reduced survival after relapse. This trial was registered on www.controlled-trials.com as ISRCTN06413384.
Blood 10/2009; 115(6):1113-20. · 9.90 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Recent literature suggests that after non-myeloablative allogeneic (NMA) stem cell transplantation (SCT), the incidence of extramedullary (EM) relapse in multiple myeloma (MM) patients is increased and that these relapses have a poor prognosis. However, numbers on incidence and treatment outcome are scarce. We collected data from 54 relapsed MM patients from a total group of 172 treated with sequential autologous and allogeneic NMA SCT at seven transplantation centres. There were 43 (79.6%) systemic relapses, including 6 with concurrent EM localisation. Five patients had a local EM relapse only. Six patients relapsed with only bone involvement. Patients with deletion of chromosome 13 had a higher incidence of EM relapse (30.8 versus 5.6%, P=0.06). EM relapses were treated with donor lymphocyte infusion, radiotherapy, or chemotherapy, especially with novel agents. The response rate was 45.5%, which was not different when compared to patients without EM disease (54.1%). Overall survival and progression-free survival were not significantly different in patients with EM disease, when compared to those without EM disease. In conclusion, the incidence of relapse with EM disease following allogeneic NMA SCT was 20.4%. There was no negative impact of EM relapse on response rate, overall survival and progression-free survival.
Bone Marrow Transplantation 06/2008; 41(9):779-84. · 3.75 Impact Factor
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H.M. Lokhorst,
B van der Holt, S Zweegman,
E Vellenga,
S. Croockewit,
M.H. Oers,
P. von dem Borne,
P Wijermans,
R. Schaafsma,
O de Weerdt, [......],
H. Berenschot,
G M Bos,
K-S.G. Jie,
H. Sinnige,
M van Marwijk Kooy,
P Joosten,
M C Minnema,
R. van Ammerlaan,
x HOVON Dutch-Belgian Hematology-Oncology Group,
P Sonneveld
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E. Kneppers,
H.M. Lokhorst,
C.M. Eeltink,
G Huls,
M J Kersten,
J. Koedam,
M C Minnema,
M.H.J. van Oers,
R.A.P. Raymakers,
M R Schaafsma,
E Vellenga,
P W Wijermans,
S. Wittebol,
P Sonneveld, S Zweegman
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A. Broyl,
D Hose,
H.M. Lokhorst,
Y. de Knegt,
J. Peeters,
A Jauch,
U. Bertsch,
A. Buijs,
M. Stevens-Kroef,
H B Beverloo,
E Vellenga, S Zweegman,
M J Kersten,
B van der Holt,
L. el Jarari,
G. Mulligan,
H Goldschmidt,
M. van Duin,
P Sonneveld
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H.M. Lokhorst,
I G Schmidt-Wolf,
P Sonneveld,
B van der Holt,
H Martin,
R.M. Barge,
U. Bertsch,
J. Schlenzka,
G.M.J. Bos,
S. Croockewit, [......],
H. Sinnige,
I. Blau,
M Delforge,
O de Weerdt,
P Wijermans,
S. Wittebol,
U. Duersen,
E Vellenga,
H Goldschmidt,
Ducht-Belgian HOVON German GMMG
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M Engelhardt,
J Udi,
M Kleber,
A. Spencer,
A Rocci,
S Knop,
B Bruno,
S Bringhen,
J A Pérez-Simón, S Zweegman, [......],
H.M. Lokhorst,
R. Hájek,
G Morgan,
M Boccadoro,
H Ludwig,
M Cavo,
A Polliack,
P Sonneveld,
H Einsele,
A Palumbo
