11 research outputs found
Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial
[EN]The purpose of this study was to confirm overall survival (OS) and other clinical benefits with bortezomib, melphalan, and prednisone (VMP) versus melphalan and prednisone (MP) in the phase III VISTA (Velcade as Initial Standard Therapy in Multiple Myeloma) trial after prolonged follow-up, and evaluate the impact of subsequent therapies.
Previously untreated symptomatic patients with myeloma ineligible for high-dose therapy received up to nine 6-week cycles of VMP (n = 344) or MP (n = 338).
With a median follow-up of 36.7 months, there was a 35% reduced risk of death with VMP versus MP (hazard ratio, 0.653; P < .001); median OS was not reached with VMP versus 43 months with MP; 3-year OS rates were 68.5% versus 54.0%. Response rates to subsequent thalidomide- (41% v 53%) and lenalidomide-based therapies (59% v 52%) appeared similar after VMP or MP; response rates to subsequent bortezomib-based therapy were 47% versus 59%. Among patients treated with VMP (n = 178) and MP (n = 233), median survival from start of subsequent therapy was 30.2 and 21.9 months, respectively, and there was no difference in survival from salvage among patients who received subsequent bortezomib, thalidomide, or lenalidomide. Rates of adverse events were higher with VMP versus MP during cycles 1 to 4, but similar during cycles 5 to 9. With VMP, 79% of peripheral neuropathy events improved within a median of 1.9 months; 60% completely resolved within a median of 5.7 months.
VMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent antimyeloma therapy. First-line bortezomib use does not induce more resistant relapse. VMP used upfront appears more beneficial than first treating with conventional agents and saving bortezomib- and other novel agent-based treatment until relapse
A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia
Sotatercept in patients with osteolytic lesions of multiple myeloma
This phase IIa study evaluated the safety and tolerability of
sotatercept, and its effects on bone metabolism and haematopoiesis in
newly diagnosed and relapsed multiple myeloma (MM) patients. Patients
were randomized (4:1) to receive four 28-d cycles of sotatercept (01,
03, or 05mg/kg) or placebo. Patients also received six cycles of
combination oral melphalan, prednisolone, and thalidomide (MPT). Thirty
patients were enrolled; six received placebo and 24 received
sotatercept. Overall, 25% of patients received all four sotatercept
doses; 71% of sotatercept-treated patients had 1 dose interruption
mainly due to increases in haemoglobin levels. Grade 3 adverse events
(AEs) were reported in 17% of patients receiving placebo and 58%
receiving sotatercept. Grade 4 AEs in sotatercept-treated patients were
neutropenia, granulocytopenia, and atrial fibrillation (one patient
each). In patients without bisphosphonate use, anabolic improvements in
bone mineral density and in bone formation relative to placebo occurred,
whereas bone resorption was minimally affected. Increases in haemoglobin
levels, versus baseline, and the duration of the increases, were higher
in the sotatercept-treated patients, with a trend suggesting a
dose-related effect. Multiple doses of sotatercept plus MPT appear to be
safe and generally well-tolerated in MM patients
Characterization of Patients with Multiple Myeloma Achieving Complete Response to Bortezomib: An Interim Report From An International Electronic Observational Study.
Characterization of Patients with Multiple Myeloma Achieving Complete Response to Bortezomib: An Interim Report From An International Electronic Observational Study.
Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.
Bortezomib plus melphalan-prednisone was superior to melphalan-prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy. (ClinicalTrials.gov number, NCT00111319.
Bortezomib Plus Melphalan and Prednisone Compared With Melphalan and Prednisone in Previously Untreated Multiple Myeloma: Updated Follow-Up and Impact of Subsequent Therapy in the Phase III VISTA Trial
Purpose
The purpose of this study was to confirm overall survival (OS) and other
clinical benefits with bortezomib, melphalan, and prednisone (VMP)
versus melphalan and prednisone (MP) in the phase III VISTA (Velcade as
Initial Standard Therapy in Multiple Myeloma) trial after prolonged
follow-up, and evaluate the impact of subsequent therapies.
Patients and Methods
Previously untreated symptomatic patients with myeloma ineligible for
high-dose therapy received up to nine 6-week cycles of VMP (n = 344) or
MP (n = 338).
Results
With a median follow-up of 36.7 months, there was a 35% reduced risk of
death with VMP versus MP (hazard ratio, 0.653; P < .001); median OS was
not reached with VMP versus 43 months with MP; 3-year OS rates were
68.5% versus 54.0%. Response rates to subsequent thalidomide( 41% v
53%) and lenalidomide-based therapies (59% v 52%) appeared similar
after VMP or MP; response rates to subsequent bortezomib-based therapy
were 47% versus 59%. Among patients treated with VMP (n = 178) and MP
(n = 233), median survival from start of subsequent therapy was 30.2 and
21.9 months, respectively, and there was no difference in survival from
salvage among patients who received subsequent bortezomib, thalidomide,
or lenalidomide. Rates of adverse events were higher with VMP versus MP
during cycles 1 to 4, but similar during cycles 5 to 9. With VMP, 79%
of peripheral neuropathy events improved within a median of 1.9 months;
60% completely resolved within a median of 5.7 months.
Conclusion
VMP significantly prolongs OS versus MP after lengthy follow-up and
extensive subsequent antimyeloma therapy. First-line bortezomib use does
not induce more resistant relapse. VMP used upfront appears more
beneficial than first treating with conventional agents and saving
bortezomib- and other novel agent-based treatment until relapse
Ofatumumab plus fludarabine and cyclophosphamide in relapsed chronic lymphocytic leukemia: results from the COMPLEMENT 2 trial
Persistent Overall Survival Benefit and No Increased Risk of Second Malignancies With Bortezomib-Melphalan-Prednisone Versus Melphalan-Prednisone in Patients With Previously Untreated Multiple Myeloma
Purpose
This final analysis of the phase III VISTA trial (Velcade As Initial
Standard Therapy in Multiple Myeloma: Assessment With Melphalan and
Prednisone) was conducted to determine whether the overall survival (OS)
benefit with bortezomib-melphalan-prednisone (VMP) versus
melphalan-prednisone (MP) in patients with myeloma who were ineligible
for transplantation was maintained after 5 years of follow-up and to
explore the risk of second primary malignancies.
Patients and Methods
In all, 682 patients received up to nine 6-week cycles of VMP or MP and
were then observed every 12 weeks or less. Data on second primary
malignancies were collected by individual patient inquiries at all sites
from 655 patients.
Results
After median follow-up of 60.1 months (range, 0 to 74 months), there was
a 31% reduced risk of death with VMP versus MP (hazard ratio [HR],
0.695; P < .001; median OS 56.4 v 43.1 months). OS benefit with VMP was
seen across prespecified patient subgroups (age >= 75 years, stage III
myeloma, creatinine clearance < 60 mL/min). Sixty-three percent of VMP
patients and 73% of MP patients had received subsequent therapy. Time
to next therapy (median, 30.7 v 20.5 months; HR, 0.557; P < .001) was
longer with VMP than with MP. Among patients who received subsequent
therapies, survival from start of subsequent therapy was similar
following VMP (median, 28.1 months) or MP (median, 26.8 months; HR,
0.914). Following VMP/MP, incidence proportions of hematologic
malignancies (1%/1%) and solid tumors (5%/3%) and exposure-adjusted
incidence rates (0.017/0.013 per patient-year) were similar and were
consistent with background rates.
Conclusion
VMP resulted in a significant reduction in risk of death versus MP that
was maintained after 5 years’ follow-up and despite substantial use of
novel-agent-based salvage therapies. There is no emerging safety signal
for second primary malignancies following VMP. J Clin Oncol 31:448-455.
(C) 2012 by American Society of Clinical Oncolog