Phase 2 studies of lenalidomide, subcutaneous bortezomib, and dexamethasone as induction therapy in patients with newly diagnosed multiple myeloma.

Autor: O'Gorman P; Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland.; Cancer Trials Ireland, Dublin, Ireland., Laubach JP; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, Massachusetts, USA., O'Dwyer ME; Department of Haematology, University Hospital Galway, Galway, Ireland., Krawczyk J; Department of Haematology, University Hospital Galway, Galway, Ireland., Yee AJ; Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA., Gilligan O; Department of Haematology, Cork University Hospital, Cork, Ireland., Cahill MR; Department of Haematology, Cork University Hospital, Cork, Ireland., Rosenblatt J; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA., Quinn J; Department of Haematology, Beaumont Hospital, Dublin, Ireland., Murphy PT; Department of Haematology, Beaumont Hospital, Dublin, Ireland., DiPietro H; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, Massachusetts, USA., Perera MR; Department of Haematology, Midlands Regional Hospital, Tullamore, Ireland., Crotty GM; Department of Haematology, Midlands Regional Hospital, Tullamore, Ireland., Cummings K; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, Massachusetts, USA., Hayden PJ; Department of Haematology, St James's Hospital, Dublin, Ireland., Browne P; Department of Haematology, St James's Hospital, Dublin, Ireland., Savell A; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, Massachusetts, USA., O'Leary HM; Department of Haematology, University Hospital Limerick, Limerick, Ireland., O'Keeffe D; Department of Haematology, University Hospital Limerick, Limerick, Ireland., Masone K; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, Massachusetts, USA., Hennessy BJ; Department of Haematology, University Hospital Waterford, Waterford, Ireland., Guerrero Garcia T; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, Massachusetts, USA., Scott K; Cancer Trials Ireland, Dublin, Ireland., Saeed K; Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland., Bianchi G; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, Massachusetts, USA., Dowling P; Department of Biology, Maynooth University, Maynooth, Kildare, Ireland., Tierney C; Department of Biology, Maynooth University, Maynooth, Kildare, Ireland., Richardson PG; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: American journal of hematology [Am J Hematol] 2022 May; Vol. 97 (5), pp. 562-573. Date of Electronic Publication: 2022 Feb 18.
DOI: 10.1002/ajh.26491
Abstrakt: There are limited prospective data on lenalidomide, subcutaneous bortezomib, and dexamethasone (RsqVd) in transplant-eligible/transplant-ineligible patients with newly diagnosed multiple myeloma. Reliable biomarkers for efficacy and toxicity are required to better tailor therapy. Two parallel studies were conducted by Cancer Trials Ireland (CTI; NCT02219178) and the Dana-Farber Cancer Institute (DFCI; NCT02441686). Patients received four 21-day cycles of RsqVd and could then receive either another 4 cycles of RsqVd or undergo autologous stem cell transplant. Postinduction/posttransplant, patients received lenalidomide maintenance, with bortezomib included for high-risk patients. The primary endpoint was overall response rate (ORR) after 4 cycles of RsqVd. Eighty-eight patients were enrolled and 84 treated across the two studies; median age was 64.7 (CTI study) and 60.0 years (DFCI study), and 59% and 57% had stage II-III disease. Pooled ORR after 4 cycles in evaluable patients was 93.5%, including 48.1% complete or very good partial responses (CTI study: 91.9%, 59.5%; DFCI study: 95.0%, 37.5%), and in the all-treated population was 85.7% (44.0%). Patients received a median of 4 (CTI study) and 8 (DFCI study) RsqVd cycles; 60% and 31% of patients (CTI study) and 33% and 51% of patients (DFCI study) underwent transplant or received further RsqVd induction, respectively. The most common toxicity was peripheral neuropathy (pooled: 68%, 7% grade 3-4; CTI study: 57%, 7%; DFCI study: 79%, 7%). Proteomics analyses indicated elevated kallikrein-6 in good versus poor responders, decreased midkine in good responders, and elevated macrophage inflammatory protein 1-alpha in patients who stopped treatment from neurotoxicity, suggesting predictive biomarkers warranting further investigation.
(© 2022 Wiley Periodicals LLC.)
Databáze: MEDLINE
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