Natural History of Relapsed Myeloma, Refractory to Immunomodulatory Drugs and Proteasome Inhibitors: A Multicenter IMWG Study

• Main Authors: Kumar, Shaji, Dimopoulos, Meletios A, Kastritis, Efstathios, Terpos, Evangelos, Nahi, Hareth, Goldschmidt, Hartmut, Hillengass, Jens, Leleu, Xavier, Beksac, Meral, Alsina, Melissa, Oriol, Albert, Cavo, Michele, Ocio, Enrique M., Mateos, Maria Victoria, O'Donnell, Elizabeth K., Vij, Ravi, Lokhorst, Henk M., van de Donk, Niels W.C.J., Min, Chang-Ki, Mark, Tomer, Turesson, Ingemar, Hansson, Markus, Ludwig, Heinz, Jagannath, Sundar, Delforge, Michel, Kyriakou, Charalampia, Hari, Parameswaran, Mellqvist, Ulf-Henrik, Usmani, Saad Z, Dytfeld, Dominik, Badros, Ashraf Z, Moreau, Philippe, Kim, Kihyun, Rodriguez Otero, Paula, Lee, Jae Hoon, Shustik, Chaim, Waller, Daniel, Chng, Wee Joo, Ozaki, Shuji, Lee, Je-Jung, de la Rubia, Javier, Eom, Hyeon Seok, Rosinol, Laura, Lahuerta, Juan José, Sureda, Anna, Kim, Jin Seok, Durie, Brian G.M.
• Format: Conference Proceeding
• Language: English
• Subjects: Medicin och hälsovetenskap
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.4414.4414

Background: Treatment of multiple myeloma has evolved considerably in the past few years with availability of several news drugs as well as increasing use of multidrug combinations. These changes have no doubt led to the improved survival seen among patients with MM. We have previously shown that outcomes of patients intolerant or refractory to one of the IMiDs and bortezomib had a poor outcome. Since that time, other drugs of the same class as well as new classes of drugs have been introduced for the treatment of MM. We designed this retrospective study to estimate the outcomes in patients with relapsed myeloma, who have become refractory to the current generation IMiDs and proteasome inhibitors. Patients and Methods: Patients with relapsed multiple myeloma who have received at least 3 prior lines of therapy, is refractory to both an IMiD (lenalidomide or pomalidomide) AND a proteasome inhibitor (bortezomib or carfilzomib), and has been exposed to an alkylating agent were identified from multiple centers. The time patients met the above criteria was defined as T0, and details of all treatment regimens before and after T0 were collected using electronic CRFs. The study was approved by the IRB at the respective centers. Results: 543 patients were enrolled in this study; median age was 62 years (31-87) and 61% were males. Patients were enrolled from centers in North America (n=181), Europe (n=318), and Asia Pacific (n=44). Patients were diagnosed between 2006 and 2014, the median duration between diagnosis of myeloma and study entry (T0) was 3.1 years (0.3 to 9). The median (95% CI) estimated follow up from diagnosis and from T0 were 61 (57, 66) months and 13 (11, 15) months respectively. The median number of lines of therapy prior to T0 was 4 (3-13), 48% had a prior transplant. The median OS from T0 for the entire cohort was 13 (11, 15) months. For these 462 patients, the median number of recorded regimens was 2 (1-9). The overall response and the depth of response to each line of treatment following T0 are as shown in the table. The median (95% CI) PFS and OS from T0 was 5 (4, 6), and 15.2 (13, 17), respectively. The overall survival for the 81 patients with no treatment post T0 was only 2.1 months. In a multivariate analysis, duration from diagnosis to T0, ISS stage III and number of lines of therapy were all associated with inferior PFS, as well as OS, and in addition, serum creatinine>2 mg/dL at T0 also predicted inferior OS. Conclusions: The study prov