10 research outputs found
P1685: PATIENTSâ PREFERENCES FOR MULTIPLE MYELOMA (MM) TREATMENT INITIATION AND DISCONTINUATION IN THE US
Phase 1/1b Pharmacokinetic (PK) and Safety Study of the Investigational Oral Proteasome Inhibitor (PI) Ixazomib in Relapsed/Refractory Multiple Myeloma (RRMM) Patients (Pts) with Severe Renal Impairment or End-Stage Renal Disease (ESRD) Requiring Hemodialysis
P892: ANALYSIS OF INFECTIONS AND PARAMETERS OF HUMORAL IMMUNITY IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM) TREATED WITH TALQUETAMAB (TAL) MONOTHERAPY IN MONUMENTAL-1
Selinexor-Based Triplet Regimens in Patients With Multiple Myeloma Previously Treated With Anti-CD38 Monoclonal Antibodies.
BACKGROUND: The increasing use of anti-CD38 monoclonal antibodies (αCD38 mAbs) for newly diagnosed or early relapsed multiple myeloma (MM), especially in non-transplant eligible patients, may lead to more patients developing αCD38 mAb-refractory disease earlier in the treatment course with fewer treatment options.
PATIENTS AND METHODS: We analyzed the efficacy and safety of selinexor-based triplets (selinexor+dexamethasone [Sd] plus pomalidomide [SPd, n = 23], bortezomib [SVd, n = 16] or carfilzomib (SKd, n = 23]) in a subset of STOMP (NCT02343042) and BOSTON (NCT03110562) study patients treated previously with αCD38 mAbs.
RESULTS: Sixty-two patients (median 4 prior therapies, range 1 to 11, 90.3% refractory to αCD38 mAb) were included. Overall response rates (ORR) in the SPd, SVd and SKd cohorts were 52.2%, 56.3%, and 65.2%, respectively. Overall response rate was 47.4% among patients who had MM refractory to the third drug reintroduced in the Sd-based triplet. Median progression-free survival in the SPd, SVd, and SKd cohorts was 8.7, 6.7, and 15.0 months, respectively, and median overall survival was 9.6, 16.9, and 33.0 months, respectively. Median time to discontinuation in the SPd, SVd, and SKd cohorts was 4.4, 5.9, and 10.6 months, respectively. The most common hematological adverse events were thrombocytopenia, anemia, and neutropenia. Nausea, fatigue, and diarrhea were primarily grade 1/2. Adverse events were generally manageable with standard supportive care and dose modifications.
CONCLUSION: Selinexor-based regimens may offer effective and well-tolerated therapy to patients with relapsed and/or refractory MM who had disease previously exposed or refractory to αCD38 mAb therapy and could help address the unmet clinical need in these high-risk patients
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Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients.
BackgroundProteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM).MethodsThe safety, efficacy, maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of selinexor (80 or 100âmg)â+âcarfilzomib (56 or 70âmg/m2)â+âdexamethasone (40âmg) (XKd) once weekly (QW) was evaluated in patients with relapsed refractory MM (RRMM) not refractory to carfilzomib.ResultsThirty-two patients, median prior therapies 4 (range, 1-8), were enrolled. MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and/or gain 1q. Common treatment-related adverse events (all/Grade 3) were thrombocytopenia 72%/47% (G3 and G4), nausea 72%/6%, anaemia 53%/19% and fatigue 53%/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80âmg, carfilzomib 56âmg/m2, and dexamethasone 40âmg, all QW. The overall response rate was 78% including 14 (44%)ââ„âvery good partial responses. Median progression-free survival was 15 months.ConclusionsWeekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM
Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients.
BACKGROUND: Proteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM).
METHODS: The safety, efficacy, maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of selinexor (80 or 100âmg)â+âcarfilzomib (56 or 70âmg/m
RESULTS: Thirty-two patients, median prior therapies 4 (range, 1-8), were enrolled. MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and/or gain 1q. Common treatment-related adverse events (all/Grade 3) were thrombocytopenia 72%/47% (G3 and G4), nausea 72%/6%, anaemia 53%/19% and fatigue 53%/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80âmg, carfilzomib 56âmg/m
CONCLUSIONS: Weekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM
International myeloma working group consensus recommendations on imaging in monoclonal plasma cell disorders
Recent advances in the treatment of multiple myeloma have increased the need for accurate diagnosis of the disease. The detection of bone and bone marrow lesions is crucial in the investigation of multiple myeloma and often dictates the decision to start treatment. Furthermore, detection of minimal residual disease is important for prognosis determination and treatment planning, and it has underscored an unmet need for sensitive imaging methods that accurately assess patient response to multiple myeloma treatment. Low-dose whole-body CT has increased sensitivity compared with conventional skeletal survey in the detection of bone disease, which can reveal information leading to changes in therapy and disease management that could prevent or delay the onset of clinically significant morbidity and mortality as a result of skeletal-related events. Given the multiple options available for the detection of bone and bone marrow lesions, ranging from conventional skeletal survey to whole-body CT, PET/CT, and MRI, the International Myeloma Working Group decided to establish guidelines on optimal use of imaging methods at different disease stages. These recommendations on imaging within and outside of clinical trials will help standardise imaging for monoclonal plasma cell disorders worldwide to allow the comparison of results and the unification of treatment approaches for multiple myeloma
International myeloma working group consensus recommendations on imaging in monoclonal plasma cell disorders
Recent advances in the treatment of multiple myeloma have increased the
need for accurate diagnosis of the disease. The detection of bone and
bone marrow lesions is crucial in the investigation of multiple myeloma
and often dictates the decision to start treatment. Furthermore,
detection of minimal residual disease is important for prognosis
determination and treatment planning, and it has underscored an unmet
need for sensitive imaging methods that accurately assess patient
response to multiple myeloma treatment. Low-dose whole-body CT has
increased sensitivity compared with conventional skeletal survey in the
detection of bone disease, which can reveal information leading to
changes in therapy and disease management that could prevent or delay
the onset of clinically significant morbidity and mortality as a result
of skeletal-related events. Given the multiple options available for the
detection of bone and bone marrow lesions, ranging from conventional
skeletal survey to whole-body CT, PET/CT, and MRI, the International
Myeloma Working Group decided to establish guidelines on optimal use of
imaging methods at different disease stages. These recommendations on
imaging within and outside of clinical trials will help standardise
imaging for monoclonal plasma cell disorders worldwide to allow the
comparison of results and the unification of treatment approaches for
multiple myeloma