Claudia A M Stege1, Kazem Nasserinejad2, Ellen van der Spek3, Yavuz M Bilgin4, Alain Kentos5, Maaike Sohne6, Roel J W van Kampen7, Inge Ludwig8, Noortje Thielen9, Nazik Durdu-Rayman10, Nicole C H P de Graauw11, Niels W C J van de Donk1, Esther G M de Waal12, Marie-Christiane Vekemans13, Gert Jan Timmers14, Marjolein van der Klift15, Savita Soechit16, Paul A F Geerts17, Matthijs H Silbermann18, Margriet Oosterveld19, Inger S Nijhof1, Pieter Sonneveld20, Saskia K Klein21, Mark-David Levin22, Sonja Zweegman1. 1. Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands. 2. HOVON Data Center, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. 3. Department of Internal Medicine, Rijnstate Hospital, Arnhem, the Netherlands. 4. Department of Internal Medicine, Admiraal de Ruijter Hospital, Goes, the Netherlands. 5. Department of Hematology, Centre Hospitalier Jolimont, Haine-Saint-Paul, Belgium. 6. Department of Internal Medicine/Hematology, St Antonius Hospital, Nieuwegein, the Netherlands. 7. Department of Internal Medicine, Zuyderland Medical Center, Sittard-Geleen, the Netherlands. 8. Department of Hematology, Bernhoven Hospital, Uden, the Netherlands. 9. Department of Internal Medicine, Diakonessenhuis, Utrecht, the Netherlands. 10. Department of Internal Medicine-Hematology, Franciscus Hospital location Vlietland, Schiedam, the Netherlands. 11. Department of Internal Medicine, Bravis Hospital, Roosendaal, the Netherlands. 12. Department of Internal Medicine, Medisch Centrum Leeuwarden, Leeuwarden, the Netherlands. 13. Department of Hematology, St Luc Hospital, Bruxelles, Belgium. 14. Department of Internal Medicine, Amstelland Hospital, Amstelveen, the Netherlands. 15. Department of Internal Medicine, Amphia Hospital, Breda, the Netherlands. 16. Department of Hematology, Reinier de Graaf Groep, Delft, the Netherlands. 17. Department of Internal Medicine, Deventer Hospital, Deventer, the Netherlands; Currently Isala, Zwolle, the Netherlands. 18. Department of Internal Medicine, Tergooi Hospital, Hilversum, the Netherlands. 19. Department of Internal Medicine, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands. 20. Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. 21. Department of Internal Medicine, Meander Medical Center, Amersfoort, the Netherlands. 22. Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, the Netherlands.
Abstract
PURPOSE: Frail patients with newly diagnosed multiple myeloma have an inferior outcome, mainly because of a high discontinuation rate due to toxicity. We designed a phase II trial specifically for frail patients, evaluating the efficacy and tolerability of ixazomib-daratumumab-low-dose-dexamethasone (Ixa-Dara-dex). METHODS: Sixty-five patients, who were frail according to the International Myeloma Working Group frailty index, were treated with nine induction cycles Ixa-Dara-dex followed by maintenance with Ixa-Dara for a maximum of 2 years. RESULTS: The overall response rate on induction therapy was 78%. After a median follow-up of 22.9 months, median progression-free survival (PFS) was 13.8 months and 12-month overall survival (OS) was 78%. Median PFS and 12-month OS were 21.6 months and 92% in patients who were frail based on age > 80 years alone, versus 13.8 months and 78%, and 10.1 months and 70% in patients who were frail based on additional frailty parameters either ≤ 80 or > 80 years of age, respectively. In 51% of patients, induction therapy had to be discontinued prematurely, of which 6% because of noncompliance to study treatment, 9% because of toxicity, and 9% because of death (8% within 2 months, of which 80% because of toxicity). Quality of life improved during induction treatment, being clinically meaningful already after three induction cycles. CONCLUSION: Ixa-Dara-dex lead to a high response rate and improved quality of life. However, treatment discontinuation because of toxicity and early mortality, negatively influencing PFS and OS, remains a concern in frail patients. The outcome was heterogeneous across frail subpopulations. This should be taken into account in the design and interpretation of future studies in frail patients, to pave the way for more precise treatment guidance.
PURPOSE: Frail patients with newly diagnosed multiple myeloma have an inferior outcome, mainly because of a high discontinuation rate due to toxicity. We designed a phase II trial specifically for frail patients, evaluating the efficacy and tolerability of ixazomib-daratumumab-low-dose-dexamethasone (Ixa-Dara-dex). METHODS: Sixty-five patients, who were frail according to the International Myeloma Working Group frailty index, were treated with nine induction cycles Ixa-Dara-dex followed by maintenance with Ixa-Dara for a maximum of 2 years. RESULTS: The overall response rate on induction therapy was 78%. After a median follow-up of 22.9 months, median progression-free survival (PFS) was 13.8 months and 12-month overall survival (OS) was 78%. Median PFS and 12-month OS were 21.6 months and 92% in patients who were frail based on age > 80 years alone, versus 13.8 months and 78%, and 10.1 months and 70% in patients who were frail based on additional frailty parameters either ≤ 80 or > 80 years of age, respectively. In 51% of patients, induction therapy had to be discontinued prematurely, of which 6% because of noncompliance to study treatment, 9% because of toxicity, and 9% because of death (8% within 2 months, of which 80% because of toxicity). Quality of life improved during induction treatment, being clinically meaningful already after three induction cycles. CONCLUSION:Ixa-Dara-dex lead to a high response rate and improved quality of life. However, treatment discontinuation because of toxicity and early mortality, negatively influencing PFS and OS, remains a concern in frail patients. The outcome was heterogeneous across frail subpopulations. This should be taken into account in the design and interpretation of future studies in frail patients, to pave the way for more precise treatment guidance.
Authors: Martin Dreyling; Marc André; Nicola Gökbuget; Hervé Tilly; Mats Jerkeman; John Gribben; Andrés Ferreri; Pierre Morel; Stephan Stilgenbauer; Christopher Fox; José Maria Ribera; Sonja Zweegman; Igor Aurer; Csaba Bödör; Birgit Burkhardt; Christian Buske; Maria Dollores Caballero; Elias Campo; Bjoern Chapuy; Andrew Davies; Laurence de Leval; Jeanette Doorduijn; Massimo Federico; Philippe Gaulard; Francesca Gay; Paolo Ghia; Kirsten Grønbæk; Hartmut Goldschmidt; Marie-Jose Kersten; Barbara Kiesewetter; Judith Landman-Parker; Steven Le Gouill; Georg Lenz; Sirpa Leppä; Armando Lopez-Guillermo; Elizabeth Macintyre; Maria Victoria Mateos Mantega; Philippe Moreau; Carol Moreno; Bertrand Nadel; Jessica Okosun; Roger Owen; Sarka Pospisilova; Christiane Pott; Tadeusz Robak; Michelle Spina; Kostas Stamatopoulos; Jan Stary; Karin Tarte; Allessandra Tedeschi; Catherine Thieblemont; Ralf Ulrich Trappe; Lorenz H Trümper; Gilles Salles Journal: Hemasphere Date: 2022-05-19
Authors: Davine Hofste Op Bruinink; Rowan Kuiper; Mark van Duin; Tom Cupedo; Vincent H J van der Velden; Remco Hoogenboezem; Bronno van der Holt; H Berna Beverloo; Erik T Valent; Michael Vermeulen; Francesca Gay; Annemiek Broijl; Hervé Avet-Loiseau; Nikhil C Munshi; Pellegrino Musto; Philippe Moreau; Sonja Zweegman; Niels W C J van de Donk; Pieter Sonneveld Journal: J Clin Oncol Date: 2022-03-31 Impact factor: 50.717