6 research outputs found
Phase 3 randomised study of daratumumab, bortezomib and dexamethasone (DVd) vs bortezomib and dexamethasone (Vd) in patients (pts) with relapsed or refractory multiple myeloma (RRMM): CASTOR
Pharmacokinetics (PK) and Pharmacodynamics (PD) of Subcutaneous Versus Intravenous Administration of Bortezomib in Patients with Relapsed Multiple Myeloma: Effects of Subcutaneous Injection Site and Concentration, and Patient Characteristics
Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents
B-cell maturation antigen (BCMA)–targeting therapies, including bispecific antibodies (BsAbs) and antibody-drug conjugates (ADCs), are promising treatments for multiple myeloma (MM), but disease may progress after their use. CARTITUDE-2 is a phase 2, multicohort study evaluating the safety and efficacy of cilta-cel, an anti-BCMA chimeric antigen receptor T therapy, in various myeloma patient populations. Patients in cohort C progressed despite treatment with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and noncellular anti-BCMA immunotherapy. A single cilta-cel infusion was given after lymphodepletion. The primary end point was minimal residual disease (MRD) negativity at 10−5. Overall, 20 patients were treated (13 ADC exposed; 7 BsAb exposed; 1 in the ADC group also had prior BsAb exposure). Sixteen (80%) were refractory to prior anti-BCMA therapy. At a median follow-up of 11.3 months (range, 0.6-16.0), 7 of 20 (35%) patients were MRD negative (7 of 10 [70.0%] in the MRD-evaluable subset). Overall response rate (95% confidence interval [CI]) was 60.0% (36.1-80.9). Median duration of response and progression-free survival (95% CI) were 11.5 (7.9—not estimable) and 9.1 (1.5—not estimable) months, respectively. The most common adverse events were hematologic. Cytokine release syndrome occurred in 12 (60%) patients (all grade 1-2); 4 had immune effector cell-associated neurotoxicity syndrome (2 had grade 3-4); none had parkinsonism. Seven (35%) patients died (3 of progressive disease, 4 of adverse events [1 treatment related, 3 unrelated]). Cilta-cel induced favorable responses in patients with relapsed/refractory MM and prior exposure to anti-BCMA treatment who had exhausted other therapies. This trial was registered at www.clinicaltrials.gov as NCT04133636
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