Dataset Information

Pulmonary Vein Thrombosis in a Patient With Multiple Myeloma on Treatment With Lenalidomide.

ABSTRACT: Multiple myeloma (MM) poses inherent risk of thrombosis that can be amplified by the use of immunomodulator therapy. We present a patient with MM who was being treated with lenalidomide and dexamethasone when he developed progressive dyspnea on exertion consistent with a left lower pulmonary vein thrombosis (PVT) despite use of prophylactic aspirin. The PVT was not initially seen on standard computed tomography angiogram pulmonary embolism protocol but was seen on 192-slice multidetector computed tomography angiogram for assessment of coronary calcifications 8 months later. Subsequent treatment with full dose rivaroxaban resulted in full clot resolution and symptom improvement. PVT has not been previously reported with lenalidomide therapy and may not be a forefront differential diagnosis. In such cases, a multi-modality diagnostic approach may be beneficial. Consideration should be given to escalating venous thromboembolism prophylaxis to full dose anticoagulation during increased prothrombotic windows, such as the time of treatment initiation or dose adjustments, in low bleeding risk patients.

SUBMITTER: Stawiarski KM

PROVIDER: S-EPMC8139738 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Pulmonary Vein Thrombosis in a Patient With Multiple Myeloma on Treatment With Lenalidomide.

Stawiarski Kristin M KM Patil Gourav G Witt David D Pollack Ari A

World journal of oncology 20210514 2-3

Multiple myeloma (MM) poses inherent risk of thrombosis that can be amplified by the use of immunomodulator therapy. We present a patient with MM who was being treated with lenalidomide and dexamethasone when he developed progressive dyspnea on exertion consistent with a left lower pulmonary vein thrombosis (PVT) despite use of prophylactic aspirin. The PVT was not initially seen on standard computed tomography angiogram pulmonary embolism protocol but was seen on 192-slice multidetector compute ...[more]

PMID: 34046102

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Project description:Lenalidomide (Len) plus dexamethasone (Dex) is approved for the treatment of relapsed or refractory multiple myeloma (RRMM). It is possible that single-agent Len may be effective as prolonged treatment regimen in RRMM once patients demonstrate an initial response to Len+Dex induction. Patients with RRMM who responded to first-line Len+Dex in an observational study (NCT01430546) received up to 24 cycles of either Len (25 mg/day) or Len+Dex (25 mg/day and 40 mg/week) as prolonged treatment in a subsequent phase 2 clinical trial (NCT01450215). In the observational study (N = 133), median time to response was 1.7 (range 0.6-9.6) months. A complete response to all treatments received in both studies was observed in 11% of patients; very good partial response and partial response rates were 31% and 38%, respectively. Corresponding response rates in the subgroup of patients who did not enter the phase 2 trial (n = 71) were 3%, 18%, and 39%, respectively. Rates of disease progression at 2 years in the phase 2 trial were 47% versus 31% for Len versus Len+Dex (P = 0.14). After 36 months median follow-up in surviving patients, median time to progression was not reached with Len+Dex and was 24.9 months (95% confidence interval 12.5-not calculable, P < 0.001) with Len. Three-year OS among the total observational study population was 61% (95% CI, 52-69%). The corresponding rate among patients who entered the phase 2 clinical trial was 73% (95% CI, 60-83%) and was significantly lower among those patients who achieved ≥PR but did not proceed into the phase 2 trial (55%; P = 0.01). In the phase 2 trial, OS was 73% in both treatment arms (P = 0.70). Neutropenia and thrombocytopenia were more common with prolonged (phase 2 trial) versus short-term (observational study) Len administration but remained manageable. Prolonged treatment with Len with or without Dex provides sustained, clinically relevant responses and demonstrates an acceptable safety profile.

Project description:ImportanceCarfilzomib-lenalidomide-dexamethasone therapy yields deep responses in patients with newly diagnosed multiple myeloma (NDMM). It is important to gain an understanding of this combination's tolerability and impact on minimal residual disease (MRD) negativity because this end point has been associated with improved survival.ObjectiveTo assess the safety and efficacy of carfilzomib-lenalidomide-dexamethasone therapy in NDMM and high-risk smoldering multiple myeloma (SMM).Design, setting, and participantsClinical and correlative pilot study at the National Institutes of Health Clinical Center. Patients with NDMM or high-risk SMM were enrolled between July 11, 2011, and October 9, 2013. Median follow-up was 17.3 (NDMM) and 15.9 months (SMM).InterventionsEight 28-day cycles were composed of carfilzomib 20/36 mg/m2 on days 1, 2, 8, 9, 15, and 16; lenalidomide 25 mg on days 1 through 21; and dexamethasone 20/10 mg (cycles 1-4/5-8) on days 1, 2, 8, 9, 15, 16, 22, and 23. Patients who achieved at least stable disease subsequently received 24 cycles of lenalidomide extended dosing.Main outcomes and measuresPrimary end points were neuropathy of grade 3 or greater (NDMM) and at least very good partial response rates (SMM). Minimal residual disease was also assessed.ResultsOf 45 patients with NDMM, none had neuropathy of grade 3 or greater. Of 12 patients with high-risk SMM, the most common of any-grade adverse events were lymphopenia (12 [100%]) and gastrointestinal disorders (11 [92%]). All patients with SMM achieved at least a very good partial response during the study period. Among the 28 patients with NDMM and the 12 with SMM achieving at least a near-complete response, MRD negativity was found in 28 of 28 (100% [95% CI, 88%-100%]), 11 of 12 (92% [95% CI, 62%-100%]) (multiparametric flow cytometry), 14 of 21 (67% [95% CI, 43%-85%]), and 9 of 12 (75% [95% CI, 43%-94%]) (next-generation sequencing), respectively. In patients with NDMM, 12-month progression-free survival for MRD-negative vs MRD-positive status by flow cytometry and next-generation sequencing was 100% vs 79% (95% CI, 47%-94%; P < .001) and 100% vs 95% (95% CI, 75%-99%; P = .02), respectively.Conclusions and relevanceCarfilzomib-lenalidomide-dexamethasone therapy is tolerable and demonstrates high rates of MRD negativity in NDMM, translating into longer progression-free survival in patients achieving MRD negativity. Carfilzomib-lenalidomide-dexamethasone therapy also demonstrates efficacy in high-risk SMM.

Dataset Information

Pulmonary Vein Thrombosis in a Patient With Multiple Myeloma on Treatment With Lenalidomide.

Publications

Pulmonary Vein Thrombosis in a Patient With Multiple Myeloma on Treatment With Lenalidomide.

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