| 1. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 2. |
- Zweegman, Sonja, et al.
(författare)
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Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma.
- 2016
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 127:9, s. 1109-1116
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Tidskriftsartikel (refereegranskat)abstract
- The combination of melphalan, prednisone and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma (NDMM) who are ineligible for stem-cell transplantation. Long term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone and lenalidomide, followed by lenalidomide maintenance therapy showed promising results, without severe neuropathy emerging. We randomly assigned 668 NDMM patients, ineligible for stem-cell transplantation, between nine 4-weekly cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomised phase 3 trial was undertaken by HOVON and the NMSG. The primary endpoint was progression-free survival (PFS). The accrual for the study was completed in October 19, 2012. 318 patients were randomly assigned to receive MPT-T and 319 MPR-R. After a median follow up of 36 months PFS with MPT-T was 20 months (95% CI 18-23 months) versus 23 months (95% CI 19-27 months) with MPR-R (HR 0.87 [0.72-1.04], p=0.12). Response rates were similar, with ≥VGPR 47% and 45% respectively. Hematological toxicity was more pronounced with MPR-R, especially grade 3 and 4 neutropenia: 64 versus 27%. Neuropathy ≥ grade 3 was significantly higher in the MPT-T arm; 16% versus 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 versus 17 months in MPR-R), irrespective of age. MPR-R has no advantage over MPT-T concerning efficacy. The toxicity profile differed with clinically significant neuropathy during thalidomide maintenance versus myelosuppression with MPR.
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| 3. |
- Lokhorst, Henk M, et al.
(författare)
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Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.
- 2015
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 373:13, s. 1207-1219
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Tidskriftsartikel (refereegranskat)abstract
- Background Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. Methods In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight. In part 2, the dose-expansion phase, 30 patients received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram, administered once weekly (8 doses), twice monthly (8 doses), and monthly for up to 24 months. End points included safety, efficacy, and pharmacokinetics. Results No maximum tolerated dose was identified in part 1. In part 2, the median time since diagnosis was 5.7 years. Patients had received a median of four prior treatments; 79% of the patients had disease that was refractory to the last therapy received (64% had disease refractory to proteasome inhibitors and immunomodulatory drugs and 64% had disease refractory to bortezomib and lenalidomide), and 76% had received autologous stem-cell transplants. Infusion-related reactions in part 2 were mild (71% of patients had an event of any grade, and 1% had an event of grade 3), with no dose-dependent adverse events. The most common adverse events of grade 3 or 4 (in ≥5% of patients) were pneumonia and thrombocytopenia. The overall response rate was 36% in the cohort that received 16 mg per kilogram (15 patients had a partial response or better, including 2 with a complete response and 2 with a very good partial response) and 10% in the cohort that received 8 mg per kilogram (3 had a partial response). In the cohort that received 16 mg per kilogram, the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. Conclusions Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen Research and Development and Genmab; ClinicalTrials.gov number, NCT00574288 .).
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