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      Multiagent therapy with pomalidomide, bortezomib, doxorubicin, dexamethasone, and daratumumab (“Pom‐PAD‐Dara”) in relapsed/refractory multiple myeloma

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          Abstract

          Background

          Even in the era of novel immunotherapies for multiple myeloma (MM), treatment of late‐stage relapsed/refractory (RR) patients remains challenging. The aim of our study was to analyze the efficacy and safety of the five‐drug combination pomalidomide, bortezomib, doxorubicin, dexamethasone, and daratumumab (“Pom‐PAD‐Dara”) in RRMM.

          Methods

          We retrospectively analyzed data of 56 patients with RRMM who received Pom‐PAD‐Dara between September 2016 and May 2019.

          Results

          Patients were heavily pretreated with a median of four prior lines of therapy, including autologous and allogenic stem cell transplant in 50 (89%) and six (11%) patients, respectively. The overall response rate (ORR) was 78% and we observed partial remission, very good partial remission, and complete remission in 27 (48%), 13 (23%) and four (7%) patients, respectively. Median progression‐free survival was 7 months (95% CI, 3.3‐10.7) and the median overall survival was not reached at 24 months. Adverse events grade ≥ 3 were observed 41 (73%) patients and included neutropenia (n = 28, 50%), anemia (n = 22, 39%), thrombocytopenia (n = 21, 38%), and pneumonia (n = 6, 11%).

          Conclusion

          Pom‐PAD‐Dara represents a promising multiagent regimen in heavily pretreated RRMM patients with high ORR and an acceptable safety profile.

          Abstract

          We report on our single‐center experience with a novel five drug combination pomalidomide, bortezomib, doxorubicin, dexamethasone, and daratumumab (“Pom‐PAD‐Dara”). The retrospective analysis of 56 patients showed an impressive overall response rate of 78%, including penta‐refractory patients.

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          Most cited references9

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          Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013.

          Multiple myeloma remains an incurable neoplasm of plasma cells that affects more than 20,000 people annually in the United States. There has been a veritable revolution in this disease during the past decade, with dramatic improvements in our understanding of its pathogenesis, the development of several novel agents, and a concomitant doubling in overall survival. Because multiple myeloma is a complex and wide-ranging disorder, its management must be guided by disease- and patient-related factors; emerging as one of the most influential factors is risk stratification, primarily based on cytogenetic features. A risk-adapted approach provides optimal therapy to patients, ensuring intense therapy for aggressive disease and minimizing toxic effects, providing sufficient but less intense therapy for low-risk disease. This consensus statement reflects recommendations from more than 20 Mayo Clinic myeloma physicians, providing a practical approach for newly diagnosed patients with myeloma who are not enrolled in a clinical trial. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
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            Guidelines for determination of the number of prior lines of therapy in multiple myeloma

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              Bortezomib, doxorubicin and dexamethasone in advanced multiple myeloma.

              Bortezomib has shown significant activity in myeloma. In this multicenter trial, we assessed for the first time the combination of bortezomib, doxorubicin and low-dose dexamethasone (PAd) in the treatment of relapsed/refractory myeloma. Sixty-four patients were treated for a median of four 28-day cycles (1-6). Bortezomib was given at 1.3 mg/m(2) (days 1, 4, 8, 11) and dexamethasone at 40 mg (days 1-4); 34 patients receive doxorubicin at 20 mg/m(2) (days 1, 4) while 30 patients pegylated liposomal doxorubicin at 30 mg/m(2) (day 1). Fifty-eight percent of patients had undergone prior autologous transplantation, 70% prior anthracycline and 27% prior bortezomib-based regimens. Forty-three patients (67%) achieved at least a partial response including 16 (25%) with at least a very good partial response. One-year event-free survival was 34% after PAd and 31% after the previous line of therapy (hazard ratio 1.20, 95% confidence interval 0.76-1.90, P = 0.43). One-year overall survival from the start of PAd was 66%. Grade 3-4 toxic effects included thrombocytopenia (48%), neutropenia (36%), infections (15%), anemia (13%), gastrointestinal disturbances (11%) and peripheral neuropathy (10%). Two patients had grade 3-4 cardiac heart failure. PAd is an active salvage therapy with manageable toxicity in patients with relapsed/refractory myeloma.
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                Author and article information

                Contributors
                rasche_l@ukw.de
                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                01 July 2020
                August 2020
                : 9
                : 16 ( doiID: 10.1002/cam4.v9.16 )
                : 5819-5826
                Affiliations
                [ 1 ] Department of Internal Medicine II University Hospital of Würzburg Würzburg Germany
                Author notes
                [*] [* ] Correspondence

                Leo Rasche, Department of Internal Medicine II, Würzburg University Hospital, Oberdürrbacher Street 6, D‐97080 Würzburg, Germany.

                Email: rasche_l@ 123456ukw.de

                Author information
                https://orcid.org/0000-0002-9536-9649
                Article
                CAM43209
                10.1002/cam4.3209
                7433809
                32608149
                abe6cc47-1b2f-45e3-bc4f-763e3ed40807
                © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 November 2019
                : 03 May 2020
                : 16 May 2020
                Page count
                Figures: 1, Tables: 3, Pages: 8, Words: 4828
                Funding
                Funded by: IZKF Würzburg , open-funder-registry 10.13039/501100009379;
                Award ID: Z‐3R/
                Award ID: 2
                Funded by: German Cancer Aid , open-funder-registry 10.13039/501100005972;
                Funded by: Bayerisch‐Tschechische Hochschulagentur (BTHA)
                Categories
                Original Research
                Clinical Cancer Research
                Original Research
                Custom metadata
                2.0
                August 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.6 mode:remove_FC converted:18.08.2020

                Oncology & Radiotherapy
                multiple myeloma,pom‐pad‐dara,refractory,relapse
                Oncology & Radiotherapy
                multiple myeloma, pom‐pad‐dara, refractory, relapse

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