Sara Bringhen1, Massimo Offidani2, Salvatore Palmieri3, Francesco Pisani4, Rita Rizzi5, Stefano Spada1, Andrea Evangelista6, Nicola Di Renzo7, Pellegrino Musto8, Magda Marcatti9, Roberto Vallone10, Sergio Storti11, Annalisa Bernardini1, Riccardo Centurioni12, Enrico Aitini13, Angelo Palmas14, Ombretta Annibali15, Emanuele Angelucci16, Paola Ferrando17, Anna Baraldi18, Stefano Rocco19, Alessandro Andriani20, Agostina Siniscalchi21, Valerio De Stefano22, Vittorio Meneghini23, Antonio Palumbo1, Sara Grammatico24, Mario Boccadoro1, Alessandra Larocca25. 1. Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy. 2. Clinica di Ematologia, AOU Ospedali Riuniti di Ancona, Ancona, Italy. 3. Divisione di Ematologia con Unità TMO, AO Cardarelli, Napoli, Italy. 4. Hematology and Stem Cell Transplant Unit, Regina Elena National Cancer Institute, Rome, Italy. 5. Section of Hematology with Transplantation, Department of Emergency and Organ Transplantation, University of Bari Medical School, Bari, Italy. 6. Unit of Clinical Epidemiology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino and CPO Piemonte, Torino, Italy. 7. U.O. Ematologia, P.O. V. Fazzi, Lecce, Italy. 8. Scientific Direction, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (PZ), Italy. 9. U.O. Ematologia e Trapianto di Midollo, IRCCS Ospedale San Raffaele, Milano, Italy. 10. Azienda Ospedaliera Gaetano Rummo, Immunoematologia e Trasfusione, Benevento, Italy. 11. UOC Oncoematologia Fondazione di Ricerca e Cura Giovanni Paolo II, Campobasso - Università Cattolica del Sacro Cuore, Campobasso, Italy. 12. U.O.C. Medicina Interna Civitanova Marche, Italy. 13. Struttura Complessa di Oncologia Medica ed Ematologia, Azienda Ospedaliera Carlo Poma, Mantova, Italy. 14. Divisione Ematologia, Ospedale San Francesco, Nuoro, Italy. 15. UOC Ematologia e Trapianto di Cellule Staminali, Università Campus Bio-Medico, Roma, Italy. 16. IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. 17. S.C. Oncologia, Ospedale A. Manzoni, Lecco, Italy. 18. SOC Ematologia ospedale SS Antonio e Biagio e C. Arrigo Alessandria, Italy. 19. Divisione di Ematologia, AO Cardarelli, Napoli, Italy. 20. UOSD di Ematologia, ASL Roma1, Roma, Italy. 21. UOC Ematologia Ospedale S. Eugenio Roma, Italy. 22. Istituto di Ematologia, Università Cattolica, Fondazione Policlinico Universitario A. Gemelli, Roma, Italy. 23. Hematology Unit, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. 24. Hematology, "Sapienza" University of Rome, Italy. 25. Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy. Electronic address: alessandra.larocca@unito.it.
Abstract
INTRODUCTION: Early toxic death (≤60 days of diagnosis) in elderly multiple myeloma (MM) patients is attributable to active disease, age and co-morbidities. Rate of early toxic deaths is 10% with conventional chemotherapy mainly due to infection and renal failure. Novel agents have improved MM outcome at the expense of newer toxicity. METHODS: We analyzed 1146 individual patient data to assess toxic deaths during induction treatment with first-generation novel agents thalidomide, lenalidomide, bortezomib. RESULTS: During first-line therapy, 119/1146 patients (10%) died for any cause, and 47/1146 (4%) due to toxicity, including 12/1146 (1%) early deaths. The 24-month cumulative incidence was 4.1% without any difference between bortezomib (18/503 patients, 4%) and lenalidomide (29/643patients, 5%; p = 0.31). Toxic deaths occurred in 34/1039 (3%) patients <80 years and 13/107 (12%) patients ≥80 years. Causes were cardiac events (28%), infections (26%) and vascular complications (15%). In a multivariate analysis, older age and unfavorable ISS stage increased the risk of death. CONCLUSION: First-generation novel agents significantly reduced toxic deaths compared to conventional chemotherapy. One third of deaths during first-line therapy were due to cumulative drug-related toxicities, thus supportive approaches and prevention strategies should be optimized. The higher mortality rate for toxicity in octogenarians confirms the need for a careful frailty assessment.
INTRODUCTION: Early toxic death (≤60 days of diagnosis) in elderly multiple myeloma (MM) patients is attributable to active disease, age and co-morbidities. Rate of early toxic deaths is 10% with conventional chemotherapy mainly due to infection and renal failure. Novel agents have improved MM outcome at the expense of newer toxicity. METHODS: We analyzed 1146 individual patient data to assess toxic deaths during induction treatment with first-generation novel agents thalidomide, lenalidomide, bortezomib. RESULTS: During first-line therapy, 119/1146 patients (10%) died for any cause, and 47/1146 (4%) due to toxicity, including 12/1146 (1%) early deaths. The 24-month cumulative incidence was 4.1% without any difference between bortezomib (18/503 patients, 4%) and lenalidomide (29/643patients, 5%; p = 0.31). Toxic deaths occurred in 34/1039 (3%) patients <80 years and 13/107 (12%) patients ≥80 years. Causes were cardiac events (28%), infections (26%) and vascular complications (15%). In a multivariate analysis, older age and unfavorable ISS stage increased the risk of death. CONCLUSION: First-generation novel agents significantly reduced toxic deaths compared to conventional chemotherapy. One third of deaths during first-line therapy were due to cumulative drug-related toxicities, thus supportive approaches and prevention strategies should be optimized. The higher mortality rate for toxicity in octogenarians confirms the need for a careful frailty assessment.
Authors: S Zmorzyński; S Popek-Marciniec; W Styk; M Wojcierowska-Litwin; I Korszeń-Pilecka; A Szudy-Szczyrek; S Chocholska; M Hus; A A Filip Journal: Biomed Res Int Date: 2020-06-06 Impact factor: 3.411
Authors: Mirian Brink; Kaz Groen; Pieter Sonneveld; Monique C Minnema; Annemiek Broijl; Avinash G Dinmohamed; Ellen van der Spek; Mark-David Levin; Paula F Ypma; Esther de Waal; Eduardus F M Ward Posthuma; Sonja Zweegman; Niels W C J van de Donk Journal: Blood Cancer J Date: 2021-11-11 Impact factor: 11.037
Authors: Evangelos Terpos; Monika Engelhardt; Gordon Cook; Francesca Gay; Maria-Victoria Mateos; Ioannis Ntanasis-Stathopoulos; Niels W C J van de Donk; Hervé Avet-Loiseau; Roman Hajek; Annette Juul Vangsted; Heinz Ludwig; Sonja Zweegman; Philippe Moreau; Hermann Einsele; Mario Boccadoro; Jesus San Miguel; Meletios A Dimopoulos; Pieter Sonneveld Journal: Leukemia Date: 2020-05-22 Impact factor: 12.883