Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study

S K Kumar, J H Lee, J J Lahuerta, G Morgan, P G Richardson, J Crowley, J Haessler, J Feather, A Hoering, P Moreau, X LeLeu, C Hulin, S K Klein, P Sonneveld, D Siegel, J Bladé, H Goldschmidt, S Jagannath, J S Miguel, R Orlowski, A Palumbo, O Sezer, S V Rajkumar, B G M Durie, International Myeloma Working Group, Niels Abildgaard, Rafat Abonour, Ray Alexanian, Melissa Alsina, Kenneth C Anderson, Michael Attal, Hervé Avet-Loiseau, Ashraf Badros, Dalsu Baris, Bart Barlogie, Régis Bataille, Meral Beksaç, Andrew Belch, Dina Ben-Yehuda, Bill Bensinger, P Leif Bergsagel, Jenny Bird, Joan Bladé, Mario Boccadoro, Michele Cavo, Asher Chanan-Khan, Wen Ming Chen, Tony Child, James Chim, Wee-Joo Chng, Ray Comenzo, John Crowley, William Dalton, Faith Davies, Cármino de Souza, Michel Delforge, Meletios Dimopoulos, Angela Dispenzieri, Johannes Drach, Matthew Drake, Brian G M Durie, Hermann Einsele, Theirry Facon, Dorotea Fantl, Jean-Paul Fermand, Rafael Fonseca, Gösta Gahrton, Ramón García-Sanz, Christina Gasparetto, Morie Gertz, John Gibson, Sergio Giralt, Hartmut Goldschmidt, Philip Greipp, Roman Hajek, Izhar Hardan, Parameswaran Hari, Jean-Luc Harousseau, Hiroyuki Hata, Yutaka Hattori, Tom Heffner, Joy Ho, Vania Hungria, Shinsuke Ida, Peter Jacobs, Sundar Jagannath, Hans E Johnsen, Hou Jian, Douglas Joshua, Artur Jurczyszyn, Michio Kawano, Nicolaus Kröger, Shaji Kumar, Robert A Kyle, Martha Lacy, Juan José Lahuerta, Ola Landgren, Jacob Laubach, Jae Hoon Lee, Xavier LeLeu, Suzanne Lentzsch, Henk Lokhorst, Sagar Lonial, Heinz Ludwig, Angelo Maiolino, María Mateos, Jayesh Mehta, Ulf-Henrik Mellqvist, GiamPaolo Merlini, Joseph Mikhael, Angelina Rodríguez Morales, Philippe Moreau, Gareth Morgan, Hareth Nahi, Nikhil Munshi, Ruben Niesvizky, Amara Nouel, Yana Novis, Robert Orlowski, Antonio Palumbo, Santiago Pavlovsky, Linda Pilarski, Raymond Powles, Noopur Raje, S Vincent Rajkumar, Donna Reece, Tony Reiman, Paul G Richardson, David Roodman, Laura Rosiñol, Jesús San Miguel, Orhan Sezer, Jatin J Shah, John Shaughnessy, Kazuyuki Shimizu, Chaim Shustik, David Siegel, Seema Singhal, Pieter Sonneveld, Andrew Spencer, Edward Stadtmauer, Keith Stewart, Evangelos Terpos, Patrizia Tosi, Guido Tricot, Ingemar Turesson, Ben Van Camp, Brian Van Ness, Ivan Van Riet, Isabelle Vande Broek, Karin Vanderkerken, Robert Vescio, David Vesole, Anders Waage, Michael Wang, Donna Weber, Jan Westin, Keith Wheatley, Jeffrey Zonder, S K Kumar, J H Lee, J J Lahuerta, G Morgan, P G Richardson, J Crowley, J Haessler, J Feather, A Hoering, P Moreau, X LeLeu, C Hulin, S K Klein, P Sonneveld, D Siegel, J Bladé, H Goldschmidt, S Jagannath, J S Miguel, R Orlowski, A Palumbo, O Sezer, S V Rajkumar, B G M Durie, International Myeloma Working Group, Niels Abildgaard, Rafat Abonour, Ray Alexanian, Melissa Alsina, Kenneth C Anderson, Michael Attal, Hervé Avet-Loiseau, Ashraf Badros, Dalsu Baris, Bart Barlogie, Régis Bataille, Meral Beksaç, Andrew Belch, Dina Ben-Yehuda, Bill Bensinger, P Leif Bergsagel, Jenny Bird, Joan Bladé, Mario Boccadoro, Michele Cavo, Asher Chanan-Khan, Wen Ming Chen, Tony Child, James Chim, Wee-Joo Chng, Ray Comenzo, John Crowley, William Dalton, Faith Davies, Cármino de Souza, Michel Delforge, Meletios Dimopoulos, Angela Dispenzieri, Johannes Drach, Matthew Drake, Brian G M Durie, Hermann Einsele, Theirry Facon, Dorotea Fantl, Jean-Paul Fermand, Rafael Fonseca, Gösta Gahrton, Ramón García-Sanz, Christina Gasparetto, Morie Gertz, John Gibson, Sergio Giralt, Hartmut Goldschmidt, Philip Greipp, Roman Hajek, Izhar Hardan, Parameswaran Hari, Jean-Luc Harousseau, Hiroyuki Hata, Yutaka Hattori, Tom Heffner, Joy Ho, Vania Hungria, Shinsuke Ida, Peter Jacobs, Sundar Jagannath, Hans E Johnsen, Hou Jian, Douglas Joshua, Artur Jurczyszyn, Michio Kawano, Nicolaus Kröger, Shaji Kumar, Robert A Kyle, Martha Lacy, Juan José Lahuerta, Ola Landgren, Jacob Laubach, Jae Hoon Lee, Xavier LeLeu, Suzanne Lentzsch, Henk Lokhorst, Sagar Lonial, Heinz Ludwig, Angelo Maiolino, María Mateos, Jayesh Mehta, Ulf-Henrik Mellqvist, GiamPaolo Merlini, Joseph Mikhael, Angelina Rodríguez Morales, Philippe Moreau, Gareth Morgan, Hareth Nahi, Nikhil Munshi, Ruben Niesvizky, Amara Nouel, Yana Novis, Robert Orlowski, Antonio Palumbo, Santiago Pavlovsky, Linda Pilarski, Raymond Powles, Noopur Raje, S Vincent Rajkumar, Donna Reece, Tony Reiman, Paul G Richardson, David Roodman, Laura Rosiñol, Jesús San Miguel, Orhan Sezer, Jatin J Shah, John Shaughnessy, Kazuyuki Shimizu, Chaim Shustik, David Siegel, Seema Singhal, Pieter Sonneveld, Andrew Spencer, Edward Stadtmauer, Keith Stewart, Evangelos Terpos, Patrizia Tosi, Guido Tricot, Ingemar Turesson, Ben Van Camp, Brian Van Ness, Ivan Van Riet, Isabelle Vande Broek, Karin Vanderkerken, Robert Vescio, David Vesole, Anders Waage, Michael Wang, Donna Weber, Jan Westin, Keith Wheatley, Jeffrey Zonder

Abstract

Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T(0)). The median age at diagnosis was 58 years, and time from diagnosis to T(0) was 3.3 years. Following T(0), 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T(0) in 94 patients (44%) including ≥ partial response in 69 (32%). The median overall survival and event-free survival from T(0) were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs.