Patients with relapsed and/or refractory multiple myeloma (RRMM) have poor prognosis. The STRATUS study assessed safety and efficacy of pomalidomide plus low-dose dexamethasone in the largest cohort ...to date of patients with RRMM. Patients who failed treatment with bortezomib and lenalidomide and had adequate prior alkylator therapy were eligible. Pomalidomide 4 mg was given on days 1-21 of 28-day cycles with low-dose dexamethasone 40 mg (20 mg for patients aged >75 years) on days 1, 8, 15, and 22 until progressive disease or unacceptable toxicity. Safety was the primary end point; secondary end points included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Among 682 patients enrolled, median age was 66 years, and median time since diagnosis was 5.3 years. Median number of prior regimens was 5. Most patients were refractory to both lenalidomide and bortezomib (80.2%). Median follow-up was 16.8 months; median duration of treatment was 4.9 months. Most frequent grade 3/4 treatment-emergent adverse events were hematologic (neutropenia 49.7%, anemia 33.0%, and thrombocytopenia 24.1%). Most common grade 3/4 nonhematologic toxicities were pneumonia (10.9%) and fatigue (5.9%). Grade 3/4 venous thromboembolism and peripheral neuropathy were rare (1.6% each). The ORR was 32.6%, and the median DOR was 7.4 months. Median PFS and OS were 4.6 months and 11.9 months, respectively. We present the largest trial to date evaluating pomalidomide plus low-dose dexamethasone in patients with RRMM, further confirming that this regimen offers clinically meaningful benefit and is generally well tolerated. www.Clinicaltrials.gov identifier NCT01712789.
•STRATUS (MM-010), the largest POM + LoDEX trial, confirms the regimen offers clinically meaningful benefit and is generally well tolerated.•STRATUS supports POM + LoDEX as a standard of care for patients with RRMM who have poor prognosis and high need for effective treatments.
Lenalidomide plus dexamethasone is effective in the treatment of multiple myeloma (MM) but is associated with an increased risk of venous thromboembolism (VTE). This prospective, open-label, ...randomized substudy of a phase 3 trial compared the efficacy and safety of thromboprophylaxis with low-dose aspirin (ASA) or low-molecular-weight heparin (LMWH) in patients with newly diagnosed MM, treated with lenalidomide and low-dose dexamethasone induction and melphalan-prednisone-lenalidomide consolidation. Overall, 342 patients who did not have clinical indications or contraindications to antiplatelet or anticoagulant therapy were randomly assigned to receive ASA 100 mg/d (n = 176) or LMWH enoxaparin 40 mg/d (n = 166). The incidence of VTE was 2.27% in the ASA group and 1.20% in the LMWH group. Compared with LMWH, the absolute difference in the proportion of VTE was 1.07% (95% confidence interval, −1.69-3.83; P = .452) in the ASA group. Pulmonary embolism was observed in 1.70% of patients in the ASA group and none in the LMWH group. No arterial thrombosis, acute cardiovascular events, or sudden deaths were reported. No major hemorrhagic complications were reported. In previously untreated patients with MM receiving lenalidomide with a low thromboembolic risk, ASA could be an effective and less-expensive alternative to LMWH thromboprophylaxis. This study was registered at www.clinicaltrials.gov as #NCT00551928.
Serum electrophoresis performed on admission as part of routine blood chemistry showed a monoclonal component (MC) in the gamma range which led to further investigation for suspected multiple ...myeloma. Most commonly, immunoglobulin aggregates are observed in vesicular structures derived from the dilated rough endoplasmic reticulum, the so-called Mott cells, named after F.W. Mott, a surgeon who described this peculiar feature in the brains of monkeys affected by trypanosomiasis 1. CONFLICT OF INTEREST STATEMENT No conflicts of interest to disclose.
Introduction
Ixazomib, lenalidomide, and dexamethasone (IRd) have been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) based on the results of the TOURMALINE‐MM1.
Objectives ...and Methods
We conducted a retrospective–prospective analysis of 106 RRMM patients (pts) treated with IRd in 21 centers in Northern Italy, with the aim to evaluate the efficacy and safety of IRd in real life.
Results
At IRd initiation, 34% of pts were aged ≥75 (median 72.5), 8.5% had an ECOG performance status ≥2, 54.7% of evaluable pts carried high‐risk cytogenetic abnormalities del17p and/or t(4;14) and/or t(14;16) and/or 1 g gain/amp, 60.2% had received ≥2 prior lines of therapy (pLoT), 57.5% were lenalidomide (Len)‐exposed (including both Len‐sensitive and Len‐refractory pts), and 22% were Len‐refractory. Main G ≥3 adverse events (AEs) were thrombocytopenia (16%) and neutropenia (12.3%). G ≥3 non‐hematologic AEs included infections (9.4%) and GI toxicity (diarrhea 5.7%, hepatotoxicity 2.8%), VTE, skin rash, and peripheral neuropathy were mainly G1‐2. The overall response rate was 56.4% (≥VGPR 30%). With a median follow‐up of 38 m, median PFS (mPFS) was 16 m and the 1‐year OS rate was 73%. By subgroup analysis, an extended PFS was observed for pts achieving ≥VGPR (mPFS 21.2 m), time from diagnosis to IRd ≥5 years (26.2 m), 1 pLoT (34.4 m), Len‐naïve (NR), age ≥70 (20 m). In pts exposed to Len, non‐refractory in any prior line and immediately prior to IRd, mPFS was 16 and 18 m, respectively. An inferior PFS was seen in Len‐refractory pts (4.6 m). By multivariate analysis, independent predictors of PFS were age ≥70 (HR 0.6), time from diagnosis ≥5 years (HR 0.32), refractoriness to Len in any prior line (HR 3.33), and immediately prior (HR 4.31).
Conclusion
IRd might be effective and safe in RRMM pts with an indolent disease, in early lines of treatment, and who proved Len‐sensitive, independent of age, and cytogenetic risk.
We conducted a pooled analysis of two phase III trials, RV-MM-EMN-441 and EMN01, to compare maintenance with lenalidomide-prednisone vs. lenalidomide in newly diagnosed transplant-eligible and ...-ineligible myeloma patients. Primary endpoints were progression-free survival, progression-free survival 2 and overall survival with both regimens. A secondary aim was to evaluate the impact of duration of maintenance on overall survival and on outcome after relapse. A total of 625 patients (lenalidomide-prednisone arm,
= 315; lenalidomide arm,
= 310) were analyzed. The median follow-up was 58 months. Median progression-free survival (25 vs. 19 months;
= 0.08), progression-free survival 2 (56 vs. 49 months;
= 0.9) and overall survival (73 months vs. NR;
= 0.08) were not significantly different between the two arms. Toxicity profiles of lenalidomide-prednisone and lenalidomide were similar, with the exception of neutropenia that was higher in the lenalidomide arm (grade ≥ 3: 9% vs. 19%,
< 0.001), without an increase in the rate of infections. Overall survival (median NR vs. 49 months,
< 0.001), progression-free survival from relapse (median 35 vs. 24 months,
= 0.004) and overall survival from relapse (median not reached vs. 41 months,
= 0.002) were significantly longer in patients continuing maintenance for ≥2 years. We showed that the addition of prednisone at 25 or 50 mg every other day (eod) to lenalidomide maintenance did not induce any significant advantage.
PDF
